JPH02221230A - Agent for strengthening and improving constitution - Google Patents
Agent for strengthening and improving constitutionInfo
- Publication number
- JPH02221230A JPH02221230A JP1044199A JP4419989A JPH02221230A JP H02221230 A JPH02221230 A JP H02221230A JP 1044199 A JP1044199 A JP 1044199A JP 4419989 A JP4419989 A JP 4419989A JP H02221230 A JPH02221230 A JP H02221230A
- Authority
- JP
- Japan
- Prior art keywords
- lunosine
- carnosine
- constitution
- strengthening
- bone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明はＬ−力ルノシンまたはその塩を有効成分として
含有するヒトの体質強化改善剤に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a human constitution strengthening and improving agent containing L-lunosine or a salt thereof as an active ingredient.
医学の分野で先天性、後天性虚弱体質、腺病体質、易感
染性体質、膠原病体質および老化などに対する医薬は病
態を細分化して、個に化学療法を施す対症化学療法が行
われている状態であり、確立した本質的療法はない。そ
のため発育不良、老齢化、疾病などによる体質の虚弱化
に対し、診断技術が進んだ今日、複数の診断塩の下に、
数多くの化学療法剤が投薬され、所謂薬漬け、薬物汚染
などの原因になっているのが実情である。老齢化社会に
向かう現在にあっては、体質を強化改善するということ
は早急に解決を要する課題である。In the field of medicine, medicines for congenital and acquired weak constitutions, glandular disease constitutions, susceptible constitutions, collagen disease constitutions, aging, etc. are divided into symptomatic conditions and chemotherapy is administered to each individual. condition, and there is no established essential therapy. Therefore, in today's advanced diagnostic technology, multiple diagnostic methods are used to treat weakened constitutions due to poor growth, aging, and diseases.
The reality is that many chemotherapy drugs are administered, leading to so-called drug addiction and drug contamination. As we move toward an aging society, strengthening and improving our physical constitution is an issue that requires an urgent solution.
本発明は副作用°の全くない、自然治應力を維持促進す
る、生理活性物質による体質強化改善剤を提供すること
を目的とする。An object of the present invention is to provide an agent for strengthening and improving the constitution using a physiologically active substance, which has no side effects and maintains and promotes natural healing power.
本発明者らは多年にわたる哺乳動物中に含まれるω−ア
ミノ酸の生理活性作用の研究中にその誘導体のし一力ル
ノシンに創傷治癒作用（Ｓｕｒｇｅｒｙｌｏｏ：ＰＰ８
１５〜８２１．１９８６）および免疫調節作用（特開昭
６１−１８６３２２号）があり、自然治癒を促進する生
理物質であることを見出した。さらに本発明者らは老齢
化、疾患や手術などによる体質の虚弱化、発育不良、膠
原病体質などの問題を解決するための手段を種々検討の
結果、Ｌ−力ルノシンをこれらの体質のヒトに対して与
える時は極めて優れた臨床効果を現すことを見出して本
発明を完成した。The present inventors have been researching the physiological activity of ω-amino acids contained in mammals for many years, and discovered that its derivative lunosine has a wound-healing effect (Surgeryloo: PP8).
15-821.1986) and an immunomodulatory effect (Japanese Patent Application Laid-Open No. 186322/1986), and was found to be a physiological substance that promotes natural healing. Furthermore, the present inventors have investigated various means to solve problems such as aging, weakened constitution due to disease or surgery, poor growth, and a predisposition to collagen disease. We have completed the present invention by discovering that when given to patients, extremely excellent clinical effects are exhibited.
Ｌ−力ルノシンは１９００年グレヴイチ（Ｇｕｌｅｗｉ
ｔｃｈ）らによりリービッヒの肉エキス中から発見され
た、β−アラニンとＬ−ヒスチジンよりなるジペブタイ
ドであり、哺乳動物の骨格筋中に多量に含有されている
。発見以来多くの研究が発表されているがその生理学的
存在意義は判明しなかった。L-lunosine was developed in 1900 by Gulewi.
Dipebutide, which consists of β-alanine and L-histidine, was discovered in Liebig's meat extract by J.D. tch) et al., and is contained in large amounts in the skeletal muscles of mammals. Although many studies have been published since its discovery, its physiological significance has not been clarified.
Ｌ−力ルノシンは融点２５０℃（分解）、〔α］”ｇ＝
＋ ２０．０°（Ｈ２Ｏ）で、無味、無臭の水に溶は
易い白色結晶状粉末である。次の構造式％式％
その水溶液はｐＨ８，０〜８．５である。Ｌ−力ルノシ
ンは哺乳動物の主として骨格筋中に約０，１〜０．３％
含有されている物質で、日常食肉類より食品として摂取
され、必須アミノ酸し−ヒスチジンの供給源である。ま
たＬ−ヒスチジンとβ−アラニンとから生合成される。L-lunosine has a melting point of 250℃ (decomposition), [α]”g=
+20.0° (H2O), it is a tasteless, odorless, white crystalline powder that is easily soluble in water. The following structural formula % Formula % The aqueous solution has a pH of 8.0 to 8.5. L-lunosine is present in mammals, mainly in skeletal muscles, at approximately 0.1-0.3%.
It is a substance that is ingested as food from daily meat, and is a source of the essential amino acid - histidine. It is also biosynthesized from L-histidine and β-alanine.
摂取されたし一力ルノシンは吸収後方ルノシナーゼによ
りＬ−ヒスチジンとβ−アラニンに分解されて栄養素と
なり、部はＬ−力ルノシンに再合成される〔Ｌ−力ルノ
シン生合成の中間物質としてβ−アラニル−１−メチル
−ヒスチジン（Ａｎｓｅｒｉｎｅ）がある〕。上記のご
とくＬ−力ルノシンは食品類似の安全性の高い物質であ
り、吸収後は諸臓器中に存在するカルノシナーゼにより
分解されるので、他の多くの医薬品が肝臓で代謝され、
肝機能の負担となるのとは全く異なる物質である。Ingested lunosine is decomposed into L-histidine and β-alanine by lunosinase after absorption and becomes nutrients, which are resynthesized into L-lunosine [β-as an intermediate in L-lunosine biosynthesis] Alanyl-1-methyl-histidine (Anserine)]. As mentioned above, L-lunosine is a highly safe substance similar to food, and after absorption, it is broken down by carnosinase present in various organs, so many other medicines are metabolized in the liver.
This is a completely different substance from the one that puts a burden on liver function.
つぎにＬ−力ルノシンの急性毒性について述べる。Next, the acute toxicity of L-lunosine will be described.
急性毒性
マウスを１群１０匹として種々の用量のし一力ルノシン
を腹腔内ならびに経口的に投与し、投与後５時間の急性
中毒症状を観察した。ＬＤｓｏは７２時間後の死亡数よ
りファンデアヴエルデン（Ｖａｎｄｅｒ Ｗａｅｒｄｅ
ｎ）法により算出した。Ｌ−カルノシンは投与液量が０
．１〜０．３ｍｊ！／Ｌｏｇになるよう生理食塩液に溶
解した。Acutely toxic mice (10 mice per group) were administered various doses of lunosine intraperitoneally and orally, and symptoms of acute toxicity were observed 5 hours after administration. LDso is based on the number of deaths after 72 hours.
Calculated using the method n). L-carnosine has a dosage of 0.
．． 1~0.3mj! /Log in physiological saline.
Ｌ−力ルノシンの中毒症状としては、１５．０００ｍｇ
／ｋｇ腹腔内投与（ＬＤ、。。）後約３０分頃より自発
運動の低下を招き復位をとり呼吸数は減少して不整とな
るが、正向反射あるいは逃避反射の消失はみられず、時
々挙尾反応を示したり間代性痙れんの発現をみるものが
半数にみられた。さらに症状が進むと横転を繰り返し、
接触刺戟に対して反射が昂進し痙れんの誘発がみられる
ようになり、強直性痙れんに移行し死に至った。１時間
３０分後に半数、２時間後に８０％、５時間後には金側
が死亡した。１５．０００ ｍｇ／ｋｇの経口投与後に
は殆ど影響を示さなかったが、１時間後に１０例中１例
の死亡を認めた。Symptoms of L-lunosine toxicity include 15,000mg.
Approximately 30 minutes after intraperitoneal administration (LD, . . . ) of 1 kg, locomotor activity decreased and the patient returned to the standing position, and the respiratory rate decreased and became irregular, but no loss of righting reflex or withdrawal reflex was observed. Half of the animals showed occasional tail-raising reactions or developed clonic convulsions. As the symptoms progress further, the patient may repeatedly roll over,
The patient's reflexes were heightened in response to contact stimulation, causing convulsions, which progressed to tonic convulsions and led to death. Half of them died after 1 hour and 30 minutes, 80% died after 2 hours, and the gold side died after 5 hours. After oral administration of 15,000 mg/kg, almost no effect was observed, but death was observed in 1 out of 10 patients 1 hour later.
第 １ 表
Ｌ−カルノシンのＬＤＳ。（９５％信頼限界）ＤＤＹ形
雄マウスに対する急性毒性（７２時間値）は表に示す通
りであり、Ｌ−力ルノシンは極めて毒性の低い化合物と
いえる。またＬ−カルノシンはすでに約１０年以前より
スペイン国のメルクイゴダ社において食欲不振治療剤と
して製薬化されているように、既に安全性の確認されて
いる、副作用のない物質である。Table 1 LDS of L-carnosine. (95% confidence limit) The acute toxicity (72 hour value) to DDY male mice is as shown in the table, and L-lunosine can be said to be a compound with extremely low toxicity. Furthermore, L-carnosine has already been commercialized as a drug for treating anorexia by Mercuigoda of Spain for about 10 years, and is a substance that has been confirmed to be safe and has no side effects.
Ｌ−力ルノシンの合成法は公知であり（Ｊｏｕｒｎａｌ
ｏｆ Ｂｉｏｌｏｇｉｃａｌ Ｃｈｅｍｉｓｔｒｙ、
１０８． ｐｐ７５３，１９３５）、カルボベンズオキ
シβ−アラニンを五塩化リンでクロライドとし、メタノ
ールでメチルエステルに導き、ヒドロアザイドを経てア
ザイドとなし、Ｌ−ヒスチジンメチルエステルとカップ
リングし、最後に接触還元によりカルボベンズオキシ基
をはずすことによってＬ−力ルノシンを得ることができ
る。本発明はＬ−力ルノシンの塩からなるヒトの体質強
化改善剤をも包含するが、Ｌ−力ルノシンの塩としては
カルボン酸基に基づく塩と、アミン基に基づく、薬理学
上許容される酸との酸付加塩があり、またカルボン酸基
とアミノ基の双方に基づ（塩がある。カルボン酸基に基
づく塩にはナトリウム、カリウム、カルシウム、マグネ
シウム、亜鉛、アルミニウムおよびゲルマニウムのよう
な金属との塩、アンモニウム塩および置換アンモニウム
塩、たとえばトリエチルアミンのようなトリアルキルア
ミンその他のアミンとの塩があり、アミノ基に基づく塩
には塩酸、硫酸、リン酸、酢酸、プロピオン酸、乳酸、
酒石酸、クエン酸、コハク酸、マレイン酸、ベンゼンス
ルホン酸、トルエンスルホン酸などの無機酸、有機酸と
の塩があるが、これらはそれ自体公知の方法により、遊
離のし一カルノシンを化学量論的に計算された量の、選
択された酸または塩基と反応させることによって製造す
ることができる。またＬ−力ルノシンは上記のような金
属の水酸化物との塩であってもよい。The synthesis method of L-lunosine is known (Journal
of Biological Chemistry,
108. pp. 753, 1935), carbobenzoxy β-alanine was converted to chloride with phosphorus pentachloride, converted to methyl ester with methanol, converted to azide via hydroazide, coupled with L-histidine methyl ester, and finally converted to carbobenzyl by catalytic reduction. L-lunosine can be obtained by removing the oxy group. The present invention also includes a human constitution strengthening and improving agent comprising a salt of L-lunosine, and examples of the salt of L-lunosine include a salt based on a carboxylic acid group and a pharmacologically acceptable salt based on an amine group. There are acid addition salts with acids, and salts based on both carboxylic and amino groups. Salts based on carboxylic acid groups include salts such as sodium, potassium, calcium, magnesium, zinc, aluminum and germanium. Salts with metals, ammonium salts and substituted ammonium salts, such as salts with trialkylamines and other amines such as triethylamine; salts based on amino groups include hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, propionic acid, lactic acid,
There are salts with inorganic acids and organic acids such as tartaric acid, citric acid, succinic acid, maleic acid, benzenesulfonic acid, toluenesulfonic acid, etc., and these salts can be prepared by stoichiometrically converting free carnosine using methods known per se. can be prepared by reacting with a calculated amount of the selected acid or base. Further, L-lunosine may be a salt with a metal hydroxide as described above.
臨床適用が予想される体質
前述したごとく先天性、後天性虚弱体質などの体質強化
改善、発育不良、膠原病などに関連する体質強化改善、
老齢化による生理機能の変調など従来の医薬の作用の及
ばない体質の改善が挙げられる。Constitutions that are expected to be applied clinically As mentioned above, strengthening and improving constitutions such as congenital and acquired weak constitutions, strengthening and improving constitutions related to poor growth and collagen diseases, etc.
Examples include improvements in physical constitution that are beyond the reach of conventional medicines, such as changes in physiological functions due to aging.
さらに詳細に述べると老衰による骨粗瓢症の予防と治療
、耐久力、精力、体力の減退の改善、先天性、後天性虚
弱体質、未熟児、発育不良孔、幼、小児、腺病質、気管
支喘息、アトピーなどの体質の改善、巨大外科手術後の
体力、気力の減退に対する機能回復、骨形成、骨折の修
復、リハビリテーションの効果促進などが挙げられる。More specifically, prevention and treatment of osteoporosis due to aging, improvement of decline in endurance, virility, and physical strength, congenital and acquired weak constitution, premature infants, stunted growth, infants, children, glandular pathology, and bronchial asthma. Examples include improving physical conditions such as atopic dermatitis, restoring physical strength and energy after major surgical operations, promoting bone formation, repairing fractures, and promoting the effects of rehabilitation.
推定できる臨床投与量
すでに述べたように経口投与によるし一力ルノシンのＬ
Ｄｓｏは１４．９３０ ｍｇ／ｋｇであるから極めて毒
性の少ない物質である。充分な安全を見てその１／２０
０をとるとすると７００ ｍｇ／ｋｇとなり、５０ｋｇ
の成人に換算すると３，５ｇとなるが、あとの臨床例に
も示されているとおり、これ以下の量でも充分な効果が
得られる。またＬ−カルノシンの構成成分はβ−アラニ
ンとＬ−ヒスチジンという生体内アミノ酸であり安全性
も高く副作用等の心配がなく用いられる。Estimated Clinical Dosage As mentioned above, the oral administration of lunosine L
Since Dso is 14.930 mg/kg, it is a substance with extremely low toxicity. 1/20 with sufficient safety.
If we take 0, it becomes 700 mg/kg, which is 50 kg.
This is equivalent to 3.5 g for an adult, but as shown in the later clinical examples, sufficient effects can be obtained with smaller amounts. Furthermore, the constituent components of L-carnosine are β-alanine and L-histidine, which are in vivo amino acids, and are highly safe and can be used without worrying about side effects.
Ｌ−力ルノシンの経口投与または非経口投与が都合よく
行われるものであればどんな剤形のものであってもよく
、例えば注射剤、粉末剤、顆粒剤、錠剤、カプセル剤、
腸溶剤、トローチ、などの種々の剤形をあげることが出
来るが、これらを症状に応じてそれぞれ単独で、または
組み合せで使用する。投与量は投与経路、剤形、症状な
どにより大きく変わることは当然である。本発明の体質
強化改善剤の典型的な剤形、投与量、及び投与方法を例
示すると次のごとくである。L-lunosine may be in any dosage form that is convenient for oral or parenteral administration, such as injections, powders, granules, tablets, capsules, etc.
Various dosage forms such as enteric coated agents and troches can be used, and these may be used alone or in combination depending on the symptoms. It goes without saying that the dosage varies greatly depending on the route of administration, dosage form, symptoms, etc. Typical dosage forms, dosages, and administration methods of the constitution strengthening and improving agent of the present invention are illustrated as follows.
第２表
なお、ここに記述した用法、用量は単なる目安であり、
Ｌ−力ルノシンは前述のように極めて安全な物質である
から症例により適宜増減することは何等差し支えない。Table 2 Please note that the usage and dosage described here are just a guideline.
As mentioned above, L-lunosine is an extremely safe substance, so there is no problem in increasing or decreasing the dose as appropriate depending on the case.
Ｌ−力ルノシンは水に易溶であるため、食塩水を使用し
て、無菌的操作のもとに容易にＬ−カルノシンの、例え
ば ０．３％、０．５％、１％または５％の等張溶液を
つくることができる。これを不活性ガス気流下にアンプ
ルまたはバイアル瓶に凍結乾燥して封入したし一力ルノ
シン粉末を注射直前に０．３％、０，５％、１％または
５％の等張溶液として直ちに注射に使用してもよい。Since L-carnosine is readily soluble in water, it can be easily dissolved under aseptic operation using saline solution, e.g. 0.3%, 0.5%, 1% or 5% of L-carnosine. You can make an isotonic solution of This was lyophilized and sealed in an ampoule or vial under a stream of inert gas, and the Ichiriki Lunosine powder was immediately injected as a 0.3%, 0.5%, 1% or 5% isotonic solution immediately before injection. May be used for
粉末剤をつくるには合成したし一力ルノシンを２００メ
ツシュ程度の微粉末としてガラス容器に入れ、約１２０
℃の温度で数時間乾熱滅菌する。To make a powder, synthesize the synthesized Ichiriki Lunosine as a fine powder of about 200 mesh and put it in a glass container.
Dry heat sterilize for several hours at a temperature of °C.
Ｌ−カルノシンの頚粒剤、錠剤またはカプセル剤は必要
により結合剤例えばシロップ、アラビアゴム、ゼラチン
、ソルビット、トラガントまたはポリビニルピロリドン
、賦形剤例えば乳糖、とうもろこしデンプン、リン酸カ
ルシウム、ソルビットまたはグリシン、潤滑剤例えばス
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、ヒドロキシプロピルメチルセルロースまたはシリ
カ、崩壊剤例えば馬鈴薯デンプン、或いは潤滑剤例えば
ラウリル硫酸ナトリウムなどを使用し当業界での慣用の
方法で製剤する。錠剤は当業界において周知の方法でコ
ーティングしてもよい。L-carnosine granules, tablets or capsules may optionally contain binders such as syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone, excipients such as lactose, corn starch, calcium phosphate, sorbitol or glycine, lubricants such as They are formulated in a manner conventional in the art using magnesium stearate, talc, polyethylene glycol, hydroxypropylmethylcellulose or silica, disintegrants such as potato starch, or lubricants such as sodium lauryl sulfate. Tablets may be coated by methods well known in the art.
製剤例１．（注射剤）
食塩水を使用し、無菌的操作の下に、合成したＬ−力ル
ノシンを５％または１％の等張液としてアンプルに充填
した。Formulation example 1. (Injection) Using saline, the synthesized L-lunosine was filled into ampoules as a 5% or 1% isotonic solution under aseptic operation.
製剤例２．（粉末剤）
合成したし一力ルノシンを電動温体を使用して微粉末と
し、局方２００メツシユの篩でふるった。Formulation example 2. (Powder) Synthesized lunosine was made into fine powder using an electric heating element, and sieved through a 200-mesh sieve.
この微粉末をガラス容器に入れ、１２１℃で３時間乾熱
滅菌して粉末剤とした。This fine powder was placed in a glass container and sterilized by dry heat at 121° C. for 3 hours to obtain a powder.
製剤例３．（頴粒剤）
合成したし一力ルノシンを用い下記処方で頚粒剤を製造
した。Formulation example 3. (Granules) Synthesized lunosine was used to produce granules according to the following formulation.
Ｌ−力ルノシン ０．２ｇ
乳糖 ０．３４ ｇ
とうもろこし澱粉 ０．４５ ｇ頚粒剤
１．００ ｇ製剤例４．（５％吸入剤）
気管支喘息の消炎、収斂、鎮咳、鎮静の目的で下記処方
で吸入剤をつくった。L-lunosine 0.2g Lactose 0.34g Corn starch 0.45g Cervical granules
1.00 g Formulation Example 4. (5% inhaler) An inhaler was prepared with the following formulation for the purpose of anti-inflammatory, astringent, antitussive, and sedative treatment of bronchial asthma.
炭酸水素ナトリウム ３．０ｇ
塩化ナトリウム ３．０ ｇ
グリセリン ３．０ｇ
Ｌ−力ルノシン １５．０ ｇ
水を加えて ３００厄
実験例１
下記の動物実験を行ない、骨粗難に及ぼすＬ−カルノシ
ンの効果を確認した。Sodium hydrogen carbonate 3.0g Sodium chloride 3.0g Glycerin 3.0g L-carnosine 15.0g Add water 300-day-old experiment example 1 The following animal experiment was conducted to determine the effect of L-carnosine on bone loss. It was confirmed.
方法
６６７７９７２２６匹を２群に分け、５８週齢まで、室
温２４±１℃、湿度５５±５％、固形飼料（三共ラボサ
ービス製Ｆ２）で飼育した。Ｌ−カルノシン投与群には
１２週齢から５８週齢まで約１０ケ月間飲水として０．
１５％Ｌ−力ルノシン水溶液を自由に摂取させた（計算
上、経口投与量としてＬ−力ルノシン２００ｍｇ／ｋｇ
／日となる）。Method 6,677,97226 animals were divided into two groups and raised at a room temperature of 24±1° C., a humidity of 55±5%, and solid feed (F2 manufactured by Sankyo Labo Service) until the age of 58 weeks. The L-carnosine-administered group received 0.0.
A 15% aqueous solution of L-lunosine was given ad libitum (calculated, the oral dose was 200 mg/kg of L-lunosine).
/ day).
Ｌ−カルノシン非投与群には水道水を与えた。The L-carnosine non-administered group was given tap water.
５８週目にそれらのマウスを断頭瀉血にて層殺し、大腿
骨を摘出した。At 58 weeks, the mice were killed by decapitation and exsanguination, and the femurs were removed.
骨粗厭の予防を目的とした時、研究上、骨強度の指標と
して、骨破断特性測定装置（飯尾電気製ＤＹＮ−１２５
５）を用いて新鮮な状態の骨の骨破断力と骨破断エネル
ギーを算出した。この方法で、Ｌ−カルノシン投与群と
非投与群の大腿骨の強度の比較検討を行った。When aiming to prevent osteoporosis, a bone fracture characteristic measuring device (DYN-125 manufactured by Iio Electric) was used as an indicator of bone strength for research purposes.
5) was used to calculate the bone breaking force and bone breaking energy of the fresh bone. Using this method, a comparative study of the strength of the femur between the L-carnosine administration group and the non-administration group was conducted.
結果は第３表のごとくであった。The results are shown in Table 3.
測定条件：
骨破断特性測定装置（飯尾電気ＤＹＮ−１２５５）試料
スペース １．０ｃｍ、 プランジャースピードｌＱｍ
ｍ／ｍ、負荷範囲 ５０．０ ｋｇ、チャートスピード
１２０ｃｍ／ｍ
実験結果
Ｌ−カルノシン投与群の方が骨破断力が１３１．７％、
骨破断エネルギーが１２７．４％と非投与群に比較して
高い値を示した。骨破断力の値が高いことは骨が硬いこ
とを示し、骨破断エネルギーの値が高いことは骨が柔軟
で弾力性に富んでいることを示している。この結果はＬ
−力レノシン投与群のマウスの大腿骨が若いことを示し
、骨粗鬆を阻止出来たことが証明出来た。Measurement conditions: Bone fracture property measuring device (Iio Electric DYN-1255) sample space 1.0 cm, plunger speed lQm
m/m, load range 50.0 kg, chart speed 120 cm/m Experimental results The bone breaking force in the L-carnosine administration group was 131.7%,
The bone fracture energy was 127.4%, which was higher than that of the non-administered group. A high value of bone breaking force indicates that the bone is hard, and a high value of bone breaking energy indicates that the bone is flexible and highly elastic. This result is L
- The femur bones of mice in the lenosine administration group were shown to be younger, proving that osteoporosis could be prevented.
実験例２
下記の動物実験を行ない、老化マウスのコレステロール
量に及ぼす影響を確認した。Experimental Example 2 The following animal experiment was conducted to confirm the effect on cholesterol levels in aging mice.
方法
ｄｄｙマウス♂２６匹を２群に分け、５８週齢まで、室
温２４±１℃、湿度５５±５％、固形飼料（三共ラボサ
ービス製Ｆ２）で飼育した。Ｌ−力レノシン投与群には
１２週齢から５８週齢まで約１０ケ月間飲水として０．
１５％Ｌ−カルノシン水溶液を自由に摂取させた（計算
上、経口投与量とてしＬ−カルノシン２００ ｍｇ／ｋ
ｇ／日となる）。Method Twenty-six female ddy mice were divided into two groups and raised at a room temperature of 24±1° C., a humidity of 55±5%, and solid feed (F2 manufactured by Sankyo Labo Service) until 58 weeks of age. The L-renosine administration group was given 0.0 ml of drinking water for approximately 10 months from 12 weeks of age to 58 weeks of age.
A 15% L-carnosine aqueous solution was given ad libitum (calculationally, the oral dose was 200 mg/k L-carnosine).
g/day).
Ｌ−力ルノシン非投与群には水道水を与えた。The L-lunosine non-administered group was given tap water.
５８週目にそれらのマウスを話頭瀉血にて屠殺した後開
腹し、臓器、血清、大腿骨、筋肉および臓器に沈着した
脂肪を可及的採集し秤量した。また、血清、肝臓および
脂肪組織の総コレステロール量、遊離コレステロール量
、エステル比、リン脂質ヲ定量した。この方法で、Ｌ−
力レノシン投与群と非投与群のコレステロール量の比較
検討を行った。At 58 weeks, the mice were sacrificed by head exsanguination, followed by laparotomy, and as much of the organs, serum, femurs, muscles, and fat deposited in the organs as possible were collected and weighed. In addition, total cholesterol content, free cholesterol content, ester ratio, and phospholipid content in serum, liver, and adipose tissue were determined. In this method, L-
A comparative study was conducted on the amount of cholesterol in the group treated with lenosine and the group not treated with lenosine.
第４表
齢の老化マウスに、Ｌ−力ルノシンを予防的に投与する
ことにより、生体内脂質の蓄積を、６８．７％阻止出来
た。Table 4 By administering L-lunosine prophylactically to aged mice, in vivo lipid accumulation could be inhibited by 68.7%.
症例１〜６
気管支喘息患者の症状改善の例
気管支喘息の症状が見られる６人の患者にＬ−カルノシ
ンを投与してその効果をｎ８Ｘした。Cases 1 to 6 Examples of symptom improvement in patients with bronchial asthma L-carnosine was administered to six patients with symptoms of bronchial asthma, and its effects were n8X tested.
気管支喘息の症状としては、喘鳴を伴った発作性の呼吸
困難を繰りかえして起こし、軽い場合は胸部の圧迫感を
伴った喘鳴のみあり、発作時は呼吸は浅く遠く頻脈動悸
あり、胸部は乾性う音及び呼気延長が見られる。Symptoms of bronchial asthma include repeated episodes of paroxysmal dyspnea accompanied by wheezing, and in mild cases there is only wheezing accompanied by a feeling of tightness in the chest; during attacks, breathing is shallow and there is distant tachycardia, and the chest is dry. A whistling sound and prolonged expiration are observed.
日本アレルギー学会気管支喘息重症度委員会による気管
支喘息重症度判定基準は下記のとおりである。The criteria for determining the severity of bronchial asthma by the Bronchial Asthma Severity Committee of the Japanese Society of Allergy are as follows.
１００−３Ｌ３＝６８．７％
通常の飼育では脂質の蓄積が非常に進む５８週Ｌ−力ル
ノシンを投与した６人の患者および症状はつぎの第６表
に示すとおりであり、治療の経過および効果の判定は第
７表に示すとおりである。100-3L3 = 68.7% The six patients who were administered L-lunosine for 58 weeks, whose lipid accumulation progresses significantly under normal feeding, and their symptoms are shown in Table 6 below, and the progress and effects of treatment. The determination is as shown in Table 7.
症例７゜
老衰せる女性の回復例
８８才の女性
老衰のためにベツドに寝たきりで、会話応答および表情
の反応もなく諸反応が極めて弱く素意も極めて低い入院
患者であった。Ｌ−カルノシン粉末剤を１日０．５ｇ内
服させ１４４日目ら１日１ｇに増量した（退院後も内服
を継続させている）。Case 7: Recovery case of a senile woman An 88-year-old woman was bedridden due to senility, had no conversational or facial responses, had very weak reactions, and had very low morale. The patient took 0.5 g of L-carnosine powder orally per day, and the dose was increased to 1 g per day from day 144 (oral administration continued even after discharge from the hospital).
７日目には素意も回復し、１日４時間程度ベツドから起
き上がれる程になり、会話応答もできる程に元気が出た
。１５５日目は院内の散歩や、軽運動によるリハビリテ
ーションに参加することが可能になるまで回復した。By the seventh day, his motivation had recovered, and he was able to get out of bed for about four hours a day, and his energy was strong enough to have a conversation. On the 155th day, the patient had recovered enough to be able to take a walk around the hospital and participate in rehabilitation through light exercise.
症例８゜
手術後の回復促進の例
５０才の男性
肝臓癌のため肝葉の摘出手術を受けた。手術の１０日前
からし一力ルノシン粉末剤を１日３ｇ内服させた。Case 8: An example of promoting recovery after surgery A 50-year-old man underwent surgery to remove a liver lobe due to liver cancer. Starting 10 days before the surgery, Ichiriki Lunosine powder was administered orally at a dose of 3 g per day.
このようなし−力ルノシンの投与の術後の経過を観察す
ると、術後の創傷部の治癒経過は極めて速やかで２日目
に抜糸することができた。抜糸当日から院内の軽い散歩
を自発的に行えるようになった。体力、気力の回復も著
しく術後２００日目退院することができた。通常の肝臓
手術後に見られる倦怠、衰弱、回復の遅延などの症状は
全く起こらなかった。退院後も１日１ｇのし一力ルノシ
ンを内服させており、体力の回復、維持も極めて順調で
ある。When observing the postoperative course of such administration of lunosine, the healing progress of the postoperative wound was extremely rapid, and the sutures could be removed on the second day. From the day the stitches were removed, the patient was able to voluntarily take a light walk around the hospital. The patient's physical strength and energy recovered significantly and he was able to be discharged from the hospital 200 days after the surgery. None of the symptoms of fatigue, weakness, or delayed recovery that are seen after normal liver surgery occurred. Even after being discharged from the hospital, the patient has been taking 1 g of Shiichiriki Lunosine per day, and his recovery and maintenance of physical strength are going extremely well.
症例９゜
骨折整形手術後の骨の修復とリハビリテーションの促進
例
６５才の男性
左膝蓋を骨折し、入院手術後にＬ−力ルノシン粉末剤を
１日２ｇ内服させた（退院後も１日１ｇの内服を継続さ
せている）。術後Ｘ線像に見る骨の修復は急速で、高年
齢にもかかわらず、Ｌ−カルノシンの投与が著名な効果
を示した。Case 9: Promoting Bone Repair and Rehabilitation After Fracture Orthopedic Surgery A 65-year-old man fractured his left patella. After hospitalization, he was given 2 g of L-lunosine powder per day (even after discharge, he continued to take 1 g per day). (I continue to take oral medication). Bone repair as seen in postoperative X-ray images was rapid, and administration of L-carnosine showed remarkable effects despite the patient's advanced age.
術後２８８日目ら開始したリハビリテーション機能の訓
練中、膝関節の伸展は速やかで極めて回復が早かった。During rehabilitation training, which began 288 days after surgery, the knee joint was able to extend quickly and recovery was extremely quick.
リハビリテーション開始１０日目後には自刃で階段を昇
降できる程度に回復した。After 10 days of rehabilitation, he had recovered enough to be able to walk up and down the stairs using his own knife.
症例１０゜
発育不良、気管支喘息、突発性発疹などの症状の改善例
１２才の男児
本人はもともと早産未熟児であったが、以後の発育も不
良で虚弱体質のまま１２才になった。気管支喘息、突発
性発疹が強かった。また風邪を引きやすく、脆弱な体質
であった。体重は同年令の男子の平均体重に達しなかっ
た。Ｌ−力ルノシン粉末剤を１日１ｇ２回分服させた。Case 10: Improvement in symptoms such as poor growth, bronchial asthma, and sudden rash The 12-year-old boy was originally born prematurely, but his subsequent growth was poor and he remained frail until he was 12 years old. He had severe bronchial asthma and sudden rash. He was also prone to catching colds and had a fragile constitution. His weight was below the average weight for boys his age. The patient was given 1 g of L-lunosine powder twice a day.
Ｌ−力ルノシン粉末剤による治療開始から４０日目には
体重は１．８ ｋｇ増加し、突発性発疹は治癒した。Ｌ
−カルノシン粉末剤の投薬を続け２．５か列目には体重
は更に増加した。２年を経過し、気管支喘息は治癒した
とみられる。体重は３６ｋｇとなり、１２才の男子の平
均体重に近くまで発育した。発育不良、脆弱体質、喘息
、突発性発疹などの症状は完全に改善された。Ｌ−力ル
ノシン粉末剤の投薬１日１ｇをひきつづき継続する。副
作用と見られる症状は全く観察されない。On the 40th day after the start of treatment with L-lunosine powder, the patient's body weight increased by 1.8 kg, and the sudden rash was cured. L
-Continuing to take Carnosine powder, my weight increased even further in the 2.5th column. Two years have passed, and his bronchial asthma appears to have been cured. He weighed 36 kg, which is close to the average weight for a 12-year-old boy. Symptoms such as poor growth, fragile constitution, asthma, and sudden rashes have completely improved. Continue to administer L-lunosine powder at 1 g per day. No symptoms seen as side effects were observed.
Ｌ−力ルノシンはヒトの老齢化による骨粗髭症、膠原病
の気管支喘息、疾患や手術による体質の虚弱化、乳、幼
、小児の発育不良などの体質強化改善、骨折の修復、突
発性発疹、喘息に極めて優れた効果を発揮するが、特に
喘息および老齢化による骨粗髭症に対する効果は著明で
ある。L-lunosine is useful for strengthening and improving constitutions such as osteoporosis due to aging, bronchial asthma due to collagen disease, weakened constitution due to disease or surgery, poor growth in breasts, infants, and children, repair of fractures, and sudden onset of symptoms. It is extremely effective against rashes and asthma, and is particularly effective against asthma and osteoporosis caused by aging.
Claims (1)
ことを特徴とするヒトの体質強化改善剤。A human constitution strengthening and improving agent characterized by containing L-carnosine or a salt thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1044199A JPH0717505B2 (en) | 1989-02-23 | 1989-02-23 | Osteoporosis preventive agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1044199A JPH0717505B2 (en) | 1989-02-23 | 1989-02-23 | Osteoporosis preventive agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02221230A true JPH02221230A (en) | 1990-09-04 |
| JPH0717505B2 JPH0717505B2 (en) | 1995-03-01 |
Family
ID=12684902
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1044199A Expired - Lifetime JPH0717505B2 (en) | 1989-02-23 | 1989-02-23 | Osteoporosis preventive agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0717505B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0495106A1 (en) * | 1989-10-02 | 1992-07-22 | Zeria Pharmaceutical Co., Ltd. | Osteogenesis promoter |
| JPH1112192A (en) * | 1997-06-18 | 1999-01-19 | Zenyaku Kogyo Kk | Osteoporosis preventive and treatment agent |
| JP2005120007A (en) * | 2003-10-16 | 2005-05-12 | Tokyoto Igaku Kenkyu Kiko | Vascularization inhibitor, therapeutic agent and prophylactic against disease followed by vascularization |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS53127835A (en) * | 1977-04-12 | 1978-11-08 | Kaneshirou Nagai | Treating agent for burn |
| JPS6016934A (en) * | 1983-07-06 | 1985-01-28 | Kaneshiro Nagai | Antineoplastic agent |
| JPS61186322A (en) * | 1985-02-13 | 1986-08-20 | Nippon Univ | Immunomodulator |
| JPS6314728A (en) * | 1986-07-03 | 1988-01-21 | Zeria Shinyaku Kogyo Kk | Preventive and remedy for hepatic disorder |
-
1989
- 1989-02-23 JP JP1044199A patent/JPH0717505B2/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS53127835A (en) * | 1977-04-12 | 1978-11-08 | Kaneshirou Nagai | Treating agent for burn |
| JPS6016934A (en) * | 1983-07-06 | 1985-01-28 | Kaneshiro Nagai | Antineoplastic agent |
| JPS61186322A (en) * | 1985-02-13 | 1986-08-20 | Nippon Univ | Immunomodulator |
| JPS6314728A (en) * | 1986-07-03 | 1988-01-21 | Zeria Shinyaku Kogyo Kk | Preventive and remedy for hepatic disorder |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0495106A1 (en) * | 1989-10-02 | 1992-07-22 | Zeria Pharmaceutical Co., Ltd. | Osteogenesis promoter |
| US5294634A (en) * | 1989-10-02 | 1994-03-15 | Zeria Pharmaceutical Co., Ltd. | Osteogenesis promoter |
| JPH1112192A (en) * | 1997-06-18 | 1999-01-19 | Zenyaku Kogyo Kk | Osteoporosis preventive and treatment agent |
| JP2005120007A (en) * | 2003-10-16 | 2005-05-12 | Tokyoto Igaku Kenkyu Kiko | Vascularization inhibitor, therapeutic agent and prophylactic against disease followed by vascularization |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0717505B2 (en) | 1995-03-01 |
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