JP4899224B2 - Arteriosclerosis improving agent - Google Patents
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本発明は加齢に基づく生理的動脈硬化に効果がある動脈硬化改善剤に関する。The present invention relates to an arteriosclerosis improving agent that is effective in aging-based physiological arteriosclerosis.
動脈硬化は生まれた時より進行すると言われ、血管内皮細胞における慢性的な炎症性増殖性病変で、癌と共に死因の二大要因です。動脈硬化には、加齢に基づく生理的な動脈硬化と、種々のリスクファクターの集積によって起こる動脈硬化とに理論的にわけることができる。（非特許文献１）リスクファクターの集積によって起こる病的な動脈硬化は、すなわち糖尿病、高血圧、高脂血漿、高尿酸血漿（非特許文献２）の適切な治療により、又禁煙、肥満、ストレス、運動不足の解消、アルコールの過剰摂取の制限により改善される。最近新しい動脈硬化指標で、血圧の影響の少ない心臓足首血管指数（ｃａｒｄｉｏ ａｎｋｌｅ ｖａｓｃｕｌａｒ−ｉｎｄｅｘ、以下ＣＡＶＩと略します。）が開発され（非特許文献３，４）、糖尿病（非特許文献５）、高血圧（非特許文献６）、高脂血漿（非特許文献７）の治療改善により、又禁煙（非特許文献８）、肥満（非特許文献９）、運動不足（非特許文献１０）、ストレスの解消（非特許文献１１）アルコールの過剰摂取の制限（非特許文献１２）によりＣＡＶＩ値の低下、すなわち動脈硬化の改善が報告されている。これ等の報告は動脈硬化を起こす病的な原因の除去による改善です。一方先に特許を取得した上皮改善剤（特願２００７−２７９６１８、特許第４３００３７０号、特許文献１）の上皮への塗布、吸入が皮膚、口腔及び気道（鼻、咽頭、喉頭、気管、気管支）性器の粘膜に好影響を及ぼし、皮膚の老化防止、アトピー性皮膚炎等の皮膚疾患の治療、歯肉炎、歯周病の予防、治療に、かぜ症候群、アレルギー性鼻炎、気管支喘息等の気道病変の治療に効果があり、又白髪の部位よりメラニン色素含有の黒色の毛髪の発生、性感覚の改善の効果を認めた。以上の様に上皮に好影響を及ぼす上皮改善剤にビタミンＢ１、Ｂ２、Ｂ６、Ｂ１２、Ｄ、パントテン酸、ニコチン酸、葉酸を追加し、動脈内皮に作用し動脈硬化を改善する内服薬を作成し、又一方加齢に基づく生理的な血管内皮の動脈硬化は老化現象の一つと考えられ、此れを予防し、かつ治療することは従来困難であったが、上記動脈硬化改善剤の内服による生理的な老化による動脈硬化への効果についてＣＡＶＩを用いて測定し、良好な加齢に基づく生理的な動脈硬化の改善効果を認めた。更に現今副作用なく、長期間使用可能な動脈内皮の硬化改善薬が求められている。Atherosclerosis is said to progress from birth, and is a chronic inflammatory proliferative lesion in vascular endothelial cells that is a major cause of death along with cancer. Atherosclerosis can be theoretically divided into physiological atherosclerosis based on aging and arteriosclerosis caused by accumulation of various risk factors. (Non-patent document 1) Pathological arteriosclerosis caused by accumulation of risk factors is caused by appropriate treatment of diabetes, hypertension, high-fat plasma, high-uric acid plasma (non-patent document 2 ), smoking cessation, obesity, stress, It is improved by eliminating lack of exercise and restricting excessive intake of alcohol. Recently, a cardio ankle vascular index (hereinafter abbreviated as CAVI), which is a new arteriosclerosis index and is less influenced by blood pressure, has been developed (Non-patent Documents 3 and 4), diabetes (Non-patent Document 5), Due to improved treatment of hypertension (non-patent document 6), high-fat plasma (non-patent document 7) , smoking cessation (non-patent document 8), obesity (non-patent document 9), lack of exercise (non-patent document 10), stress Resolution (Non-Patent Document 11) A reduction in CAVI value, that is, improvement of arteriosclerosis has been reported due to restriction of excessive intake of alcohol (Non-Patent Document 12) . These reports are improvements by eliminating the pathological causes of arteriosclerosis. On the other hand, application of epithelial improving agent (Japanese Patent Application No. 2007-279618, Japanese Patent No. 4300370, Patent Document 1) to the epithelium and inhalation of skin, oral cavity and respiratory tract (nose, pharynx, larynx, trachea, bronchus) Positive effects on genital mucous membranes, prevention of skin aging, treatment of skin diseases such as atopic dermatitis, prevention of gingivitis and periodontal disease, treatment, airway lesions such as cold syndrome, allergic rhinitis, bronchial asthma It was effective in the treatment of melanin, and the generation of black hair containing melanin pigment from the part of white hair and the effect of improving sexual sensation were recognized. Vitamin B 1 , B 2 , B 6 , B 12 , D, pantothenic acid, nicotinic acid, and folic acid are added to the epithelial improving agent that has a positive effect on the epithelium as described above, and acts on the arterial endothelium to improve arteriosclerosis. Atherosclerosis of physiological vascular endothelium based on aging is considered to be one of the aging phenomenon, and it has been difficult to prevent and treat it, but the above-mentioned improvement of arteriosclerosis The effect on the arteriosclerosis due to physiological aging due to the internal use of the agent was measured using CAVI, and the improvement effect of the physiological atherosclerosis based on good aging was recognized. Furthermore, there is a need for an arterial endothelium sclerosis improving agent that can be used for a long time without side effects.
上述の如く、動脈硬化には、加齢に基づく生理的な動脈硬化と、種々のリスクファクターの集積によって起こる動脈硬化とに理論的にわけることができる。リスクファクターの集積によって起こる病的な動脈硬化は適切な治療で、また原因の除去によりかなり改善される。しかし加齢に基づく生理的な動脈硬化は老化現象の一つと考えられるので、これを予防し且つ治療する薬剤はなかった。一方上皮改善剤は皮膚、粘膜の上皮組織への塗布、吸入により皮膚の老化防止、アトピー性皮膚炎等の皮膚疾患の治療、歯肉炎、歯周病の予防、治療に、かぜ症候群、気管支喘息の治療に効果があり、又白髪の部位よりメラニン色素含有の黒色の毛髪の発生、性感覚の改善の効果を認めた。以上の様に上皮に好影響を及ぼす上皮改善剤にビタミンＢ１，Ｂ２，Ｂ６，Ｂ１２，Ｄ２，パントテン酸，ニコチン酸，葉酸を追加し内服用動脈硬化改善剤を作成し、リスクファクターの集積によって起こる病的な動脈硬化のない成人に投与し、動脈血管内皮に作用し、加齢に基づく生理的な動脈硬化の改善に効果のある血管内皮の動脈硬化改善剤の提供を課題とした。As described above, arteriosclerosis can be theoretically divided into physiological arteriosclerosis based on aging and arteriosclerosis caused by accumulation of various risk factors. The pathologic arteriosclerosis caused by the accumulation of risk factors can be considerably improved by appropriate treatment and by eliminating the cause. However, physiologic arteriosclerosis based on aging is considered to be one of the aging phenomena, and there has been no drug for preventing and treating this. On the other hand, epithelium-improving agent is applied to skin and mucosal epithelial tissue, prevention of skin aging by inhalation, treatment of skin diseases such as atopic dermatitis, gingivitis, periodontal disease prevention, treatment, cold syndrome, bronchial asthma It was effective in the treatment of melanin, and the generation of black hair containing melanin pigment from the part of white hair and the effect of improving sexual sensation were recognized. As described above, vitamin B 1 , B 2 , B 6 , B 12 , D 2 , pantothenic acid, nicotinic acid, and folic acid are added to the epithelial improving agent that has a positive effect on the epithelium, thereby creating an arteriosclerosis improving agent for internal use. Providing an arteriosclerosis improving agent for vascular endothelium that is administered to adults without pathologic arteriosclerosis caused by accumulation of risk factors, acts on the arterial vascular endothelium, and is effective in improving physiological arteriosclerosis based on aging It was an issue.
本発明はコエンザイムＱ１０，システイン，ビタミンＡ，Ｂ１，Ｂ２，Ｂ６，Ｂ１２，Ｃ，Ｄ，Ｅ，パントテン酸，ニコチン酸，葉酸及びワクシニアウイルス接種家兎炎症皮膚抽出液を主成分とし動脈内皮に作用し、加齢に基づく生理的な動脈硬化を改善する動脈硬化改善剤。The present invention is mainly composed of coenzyme Q10, cysteine, vitamins A, B 1 , B 2 , B 6 , B 12 , C, D, E, pantothenic acid, nicotinic acid, folic acid and vaccinia virus inoculated rabbit inflammation skin extract. An agent for improving arteriosclerosis that acts on the arterial endothelium and improves physiological arteriosclerosis based on aging .
各薬剤の相互間が化学的に安定する為、また薬剤の安定吸収の為ビタミンＣ以外のコエンザイムＱ１０，Ｌシステイン．ビタミンＡ，Ｂ１，Ｂ２，Ｂ６，Ｂ１２，Ｄ，Ｅ，パントテン酸，ニコチン酸，葉酸及びワクシニアウイルス接種家兎炎症皮膚抽出液含有製剤は添加物入りの製剤を用いた。
製剤の添加物は、
コエンザイムＱ１０のアデリール錠１０には添加物として乳糖水和物，結晶セルローズ，バレイショデンプン，カルメロースカルシウム，ヒドロキシプロピルセルロース，ステアリン酸マグネシウムを含有する。
Ｌシステインのハイチオール散３２％には添加物として乳糖、葡萄糖を含有する。
ビタミンＡ，ビタミンＢ１，Ｂ２，Ｂ６，Ｂ１２、アスコルビン酸，ビタミンＤ２，ビタミンＥ，パントテン酸，ニコチン酸，葉酸にはジブチルヒドロキシトルエン，ブチルヒドロキシアニソール，安息香酸ナトリウム，デヒドロ酢酸ナトリウム，サッカリンナトリウム水和物，ソルビタン脂肪酸エステル，ゼラチン，白糖，乳糖水和物，軽質無水ケイ酸，レモン油を含有する。
ビタミンＥのユベラ顆粒には添加物として軽質無水ケイ酸、乳糖水和物、ポビドンを含有する加齢に基づく生理的な動脈硬化改善剤。Coenzyme Q10, L cysteine, etc. other than vitamin C for chemically stabilizing each drug and for stable absorption of the drug. Vitamin A, B 1 , B 2 , B 6 , B 12 , D, E, pantothenic acid, nicotinic acid, folic acid, and vaccinia virus-inoculated rabbit inflammation skin extract-containing preparation used a preparation containing additives.
The additive of the formulation is
The Adenyl tablet 10 of coenzyme Q10 contains lactose hydrate, crystalline cellulose, potato starch, carmellose calcium, hydroxypropylcellulose, and magnesium stearate as additives.
L-cysteine Hythiol powder 32% contains lactose and sucrose as additives.
Vitamin A, vitamin B 1 , B 2 , B 6 , B 12 , ascorbic acid, vitamin D 2 , vitamin E, pantothenic acid, nicotinic acid, folic acid are dibutylhydroxytoluene, butylhydroxyanisole, sodium benzoate, sodium dehydroacetate , Saccharin sodium hydrate, sorbitan fatty acid ester, gelatin, sucrose, lactose hydrate, light anhydrous silicic acid, lemon oil.
An aging-based physiological arteriosclerosis-improving agent containing light anhydrous silicic acid, lactose hydrate, and povidone as additives in vitamin E YUBERA granules.
本発明の加齢に基づく生理的な動脈硬化改善剤使用法：１日量１０ｍｌを分２、朝、夕食後内服する。（症例６の１症例のみ短期間１日１回４ｍｌ食後に内服した例外がある。） How to use physiological arteriosclerosis improving agent based on aging according to the present invention: Take 10 ml daily for 2 minutes in the morning and after dinner. (There is an exception that only one case 6 has been taken after a short 4ml meal once a day for a short period.)
加齢に基づく生理的な動脈硬化への効果
リスクファクターの集積によって起こる病的な動脈硬化は、すなわち糖尿病、高血圧、高脂血漿、高尿酸血漿の適切な治療により、又禁煙、肥満、ストレス、運動不足の解消、アルコールの過剰摂取の制限により改善されるが、これ等リスクファクターの集積の殆どなく，病的な動脈硬化の度合いの少ない男性、女性について、加齢に基づく生理的な動脈硬化への効果を検討した。Effects on aging-based physiological arteriosclerosis Pathological arteriosclerosis caused by accumulation of risk factors can be achieved by appropriate treatment of diabetes, high blood pressure, high fat plasma, high uric acid plasma, smoking cessation, obesity, stress, It is improved by eliminating exercise deficit and restricting excessive alcohol consumption. However, there is little accumulation of these risk factors, and men and women with a low degree of pathologic arteriosclerosis are physiologic arteriosclerosis based on aging. The effect on was examined.
Ｉ．加齢に基づく生理的な動脈硬化への動脈硬化改善剤（以下改善剤と略記す）の効果に就いては男性２名、女性７名に就いて検討した。I. The effect of an arteriosclerosis improving agent (hereinafter abbreviated as “improving agent”) on physiological atherosclerosis based on aging was examined in 2 men and 7 women.
１） 女性 ６２才 既往症：低色素性貧血 全治．健康．酒（−）、煙草（−）
改善剤飲用前ＣＡＶＩを２回測定し、１回目Ｒ−ＣＡＶＩ：７．５，Ｌ−ＣＡＶＩ：７．５、２回目Ｒ−ＣＡＶＩ：７．２，Ｌ−ＣＡＶＩ：７．８。ＣＡＶＩ値７．２，７．５，７．８は年令５０才代後半の血管の硬さです。改善剤飲用期間８５日でＲ−ＣＡＶＩ：６．５５，Ｌ−ＣＡＶＩ：６．６と低下した。ＣＡＶＩ値６．５５，６．６は年令３０才代後半に相当する血管の硬さです。飲用期間１２７日でＲ−ＣＡＶＩ：６．７５，Ｌ−ＣＡＶＩ：６．７５に、飲用期間１６５日でＲ−ＣＡＶＩ：７．０５，Ｌ−ＣＡＶＩ：７．０５と上昇。飲用期間２０５日でＲ−ＣＡＶＩ：７０，Ｌ−ＣＡＶＩ：６．９と変化なく、飲用期間２６８日でＲ−ＣＡＶＩ：６．５５，Ｌ−ＣＡＶＩ：６．６と再度低下した。飲用期間３０３日でＲ−ＣＡＶＩ：７．０，Ｌ−ＣＡＶＩ：７．０と、飲用期間３５２日でＲ−ＣＡＶＩ：６．９，Ｌ−ＣＡＶＩ：６．９５になり、さらに飲用期間４１１日でＲ−ＣＡＶＩ：６．４５，Ｌ−ＣＡＶＩ：６．５と低下している。ＣＡＶＩ値６．４５，６．５は年令３０才代前半に相当する血管の硬さです。（表，図１）1) Female 62 years old Past history: Hypochromic anemia Total cure. health. Sake (-), Tobacco (-)
The CAVI before taking the improver was measured twice, the first R-CAVI: 7.5, L-CAVI: 7.5, the second R-CAVI: 7.2, L-CAVI: 7.8. CAVI values 7.2, 7.5, and 7.8 are the hardness of blood vessels in the late 50s. It decreased with R-CAVI: 6.55 and L-CAVI: 6.6 in 85 days of the improving agent drinking period. CAVI values 6.55 and 6.6 are the hardness of blood vessels corresponding to those in their late 30s. Increased to R-CAVI: 6.75 and L-CAVI: 6.75 in the drinking period of 127 days, and to R-CAVI: 7.05 and L-CAVI: 7.05 in the drinking period of 165 days. In the drinking period of 205 days, there was no change to R-CAVI: 70, L-CAVI: 6.9, and in the drinking period of 268 days, it decreased again to R-CAVI: 6.55, L-CAVI: 6.6. With a drinking period of 303 days, R-CAVI: 7.0, L-CAVI: 7.0, and with a drinking period of 352 days, R-CAVI: 6.9, L-CAVI: 6.95, and a drinking period of 411 days R-CAVI: 6.45, L-CAVI: 6.5. CAVI values of 6.45 and 6.5 are the hardness of blood vessels corresponding to the early 30s. (Table, Fig. 1)
２） 女性 ４９才 既往症；低色素性貧血 酒時々１合位、煙草（−）
改善剤飲用前ＣＡＶＩを２回測定し、１回目 Ｒ−ＣＡＶＩ：７．０，Ｌ−ＣＡＶＩ：７．２、４７日後２回目 Ｒ−ＣＡＶＩ：７．１５，Ｌ−ＣＡＶＩ：７．１５、ＣＡＶＩ値７．０は年令４０才代前半の血管の硬さ、ＣＡＶＩ値７．１５，７．２は年令４０才代後半の血管の硬さです。改善剤飲用期間８９日目 Ｒ−ＣＡＶＩ：７．０，Ｌ−ＣＡＶＩ：７．０５と変化無く。飲用期間１６６日でＲ−ＣＡＶＩ：６．２５，Ｌ−ＣＡＶＩ：６．２に低下、ＣＡＶＩ値６．２５，６．２は年令３０才代前半の血管の硬さです。飲用期間２１０日でＲ−ＣＡＶＩ：６．６５，Ｌ−ＣＡＶＩ：６．８に、飲用期間２４５日でＲ−ＣＡＶＩ：６．４，Ｌ−ＣＡＶＩ：６．７、飲用期間２９７日でＲ−ＣＡＶＩ：６．９，Ｌ−ＣＡＶＩ：６．９５と軽度の上昇があり、飲用期間３２６日でＲ−ＣＡＶＩ：６．７，Ｌ−ＣＡＶＩ：６．７と年令４０才代前半の血管の硬さに低下した。飲用期間２９７日目に以前の体重５３ｋｇが５６ｋｇへと増加した。（表，図２）2) Female 49 years old Past history; Hypochromic anemia Alcohol sometimes 1 position , tobacco (-)
The CAVI before taking the improver was measured twice, the first R-CAVI: 7.0, L-CAVI: 7.2, the second time after 47 days R-CAVI: 7.15, L-CAVI: 7.15, CAVI A value of 7.0 is the hardness of the blood vessel in the early 40s and the CAVI values of 7.15 and 7.2 are the hardness of the blood vessel in the late 40s. Ingestion period of 89 days of improving agent R-CAVI: 7.0, L-CAVI: 7.05, no change. In the drinking period 166 days, R-CAVI: 6.25, L-CAVI: 6.2 decreased, CAVI values 6.25, 6.2 are the hardness of blood vessels in the early 30s. In drinking period 210 days, R-CAVI: 6.65, L-CAVI: 6.8, in drinking period 245 days, R-CAVI: 6.4, L-CAVI: 6.7, in drinking period 297 days, R- There was a slight increase in CAVI: 6.9, L-CAVI: 6.95, R-CAVI: 6.7, L-CAVI: 6.7, and blood vessels in the early 40s in the drinking period 326 days Decreased in hardness. On the 297th day of the drinking period, the previous weight of 53 kg increased to 56 kg. (Table, Fig. 2)
３） 女性 ８０才 現病歴：骨粗しょう症 治療中．酒（−）、煙草（−）
改善剤飲用前ＣＡＶＩを３回測定し、１回目Ｒ−ＣＡＶＩ：８．９５，Ｌ−ＣＡＶＩ：８．９、ＣＡＶＩ値８．９５，８．９は７０才代前半、１４２日後２回目Ｒ−ＣＡＶＩ：９．６，Ｌ−ＣＡＶＩ：９．６５、２２２日後３回目Ｒ−ＣＡＶＩ：９．２５，Ｌ−ＣＡＶＩ：９．３５に、ＣＡＶＩ値，９．６，９．６５，９．２５，９．３５は７０才代後半の血管の硬さです。改善剤飲用期間４６日でＲ−ＣＡＶＩ：９．３５，Ｌ−ＣＡＶＩ：９．３と変化無く。飲用期間７０日後Ｒ−ＣＡＶＩ：８．３５，Ｌ−ＣＡＶＩ：８．４５と低下。ＣＡＶＩ値８．３５，８．４５は６０才前半の血管の硬さです。飲用期間１０８日後Ｒ−ＣＡＶＩ：８．６，Ｌ−ＣＡＶＩ：８．６と、飲用期間１５１日後Ｒ−ＣＡＶＩ：８．９５，Ｌ−ＣＡＶＩ：９．１５となる。飲用期間１７２日後Ｒ−ＣＡＶＩ：９．３５，Ｌ−ＣＡＶＩ：９．３５と７０才代後半の血管の硬さに上昇。飲用期間１７２日目より４２日間改善剤飲用せず、その後再度服用中。飲用期間２１５日後Ｒ−ＣＡＶＩ：９．４，Ｌ−ＣＡＶＩ：９．３に，飲用期間２４５日後Ｒ−ＣＡＶＩ：９．２，Ｌ−ＣＡＶＩ：９．４と−ＣＡＶＩ値は７０才代後半の血管の硬さで経過している。（表，図３）3) Female 80 years old Current medical history: Osteoporosis Under treatment. Sake (-), Tobacco (-)
The CAVI before drinking the improver was measured 3 times. The first R-CAVI was 8.95, L-CAVI was 8.9, and the CAVI values were 8.95 and 8.9. CAVI: 9.6, L-CAVI: 9.65, the third time after 222 days R-CAVI: 9.25, L-CAVI: 9.35, CAVI value, 9.6, 9.65, 9.25, 9.35 is the blood vessel hardness in the late 70s. There was no change with R-CAVI: 9.35 and L-CAVI: 9.3 in the improving agent drinking period of 46 days. After 70 days of drinking, R-CAVI: 8.35 and L-CAVI: 8.45. CAVI values 8.35 and 8.45 are the hardness of blood vessels in the first half of 60 years. After 108 days of drinking, R-CAVI: 8.6, L-CAVI: 8.6, and after 151 days of drinking, R-CAVI: 8.95, L-CAVI: 9.15. After 172 days of drinking, R-CAVI: 9.35, L-CAVI: 9.35, and the blood vessel hardness increased in the late 70s. From the 172nd day of the drinking period, the patient has not taken the improver for 42 days and is taking it again. After 215 days of drinking, R-CAVI: 9.4, L-CAVI: 9.3, and after 245 days of drinking, R-CAVI: 9.2, L-CAVI: 9.4, and -CAVI values in the late 70s Elapsed due to the hardness of the blood vessels. (Table, Fig. 3)
４） 男性 ８５才 現病歴：甲状腺機能亢進症 メルカゾール２．５ｍｇ投与で甲状腺機能正常、本検査終了時肺癌発見．酒（−）、２０才頃より煙草２０〜３０本／日，１年前より禁煙
改善剤飲用前ＣＡＶＩを２回測定し、Ｒ−ＣＡＶＩ：１０．２，Ｌ−ＣＡＶＩ：１０．１、ＣＡＶＩ値１０．２は８０才以上，１０．１は７０才代後半の血管の硬さです。１６３日後２回目のＣＡＶＩ測定Ｒ−ＣＡＶＩ：１１．０，Ｌ−ＣＡＶＩ：１０．３と８０才以上の血管の硬さでＣＡＶＩ値上昇気味、改善剤飲用期間３５日でＲ−ＣＡＶＩ：１０．４，Ｌ−ＣＡＶＩ：９．８５に、飲用期間約７４日後Ｒ−ＣＡＶＩ：１０．０，Ｌ−ＣＡＶＩ：９．６０と７０才代後半の血管の硬さに低下があり、飲用期間約１０４日後Ｒ−ＣＡＶＩ：１０．５，Ｌ−ＣＡＶＩ：１０．２と上昇、飲用期間１３５日後Ｒ−ＣＡＶＩ：１０．１，Ｌ−ＣＡＶＩ：１０．２、飲用期間１８１日後Ｒ−ＣＡＶＩ：１０．４，Ｌ−ＣＡＶＩ：１０．２に、飲用期間２２８日後Ｒ−ＣＡＶＩ：１０．８，Ｌ−ＣＡＶＩ：１０．４と８０才以上の血管の硬さに上昇、飲用期間２７５日後Ｒ−ＣＡＶＩ：１０．３，Ｌ−ＣＡＶＩ：９．８に、飲用期間３０３日後Ｒ−ＣＡＶＩ：１０．０，Ｌ−ＣＡＶＩ：９．６に再度低下した。ＣＡＶＩ値１０．０，９．６は７０才代後半の血管の硬さです。（表，図４）4) Male 85 years old Current medical history: hyperthyroidism Mercadol 2.5 mg administration resulted in normal thyroid function. Sake (-), 20-30 cigarettes from around 20 years old, smoking cessation from 1 year ago CVI before drinking improver was measured twice, R-CAVI: 10.2, L-CAVI: 10.1, CAVI A value of 10.2 is 80 years or older, and 10.1 is the hardness of blood vessels in the late 70s. The second CAVI measurement after 163 days R-CAVI: 11.0, L-CAVI: 10.3 and the hardness of blood vessels over 80 years old, the CAVI value seems to rise, R-CAVI in the period of 35 days for taking the improving agent: 10. 4, L-CAVI: 9.85, R-CAVI: 10.0, L-CAVI: 9.60 after a drinking period of about 74 days, and there was a decrease in the hardness of blood vessels in the late 70s, and the drinking period was about 104 Day after R-CAVI: 10.5, L-CAVI: 10.2 increased, 135 days after drinking period R-CAVI: 10.1, L-CAVI: 10.2, drinking period 181 days later R-CAVI: 10.4 , L-CAVI: 10.2, R-CAVI: 10.8 after a drinking period of 228 days, L-CAVI: 10.4, increased to the hardness of blood vessels over 80 years old, R-CAVI: 275 days after the drinking period: 10 .3, L-CAVI: To 9.8 Drinking period 303 days after R-CAVI: 10.0, L-CAVI: decreased again to 9.6. CAVI values 10.0 and 9.6 are the blood vessel hardness in the late 70s. (Table, Fig. 4)
５） 女性８１才 現病歴：高血圧症（治療により血圧は正常に維持）顔面，頚部，胸背部皮膚炎．酒（−）、煙草（−）
改善剤飲用前ＣＡＶＩを２回測定し、１回目Ｒ−ＣＡＶＩ：１０．２，Ｌ−ＣＡＶＩ：９．９。ＣＡＶＩ値１０．２は８０才以上，９．９は７０才代後半の血管の硬さです。１６８日後２回目Ｒ−ＣＡＶＩ：１１．４，Ｌ−ＣＡＶＩ：１０．６５。ＣＡＶＩ値１１．４，１０．６５は８０才以上の血管の硬さです。２回目測定より２０日後改善剤飲用開始。３３日飲用後Ｒ−ＣＡＶＩ：１２．１，Ｌ−ＣＡＶＩ：１１．３と８０才以上の血管の硬さで最高値。飲用期間６３日目Ｒ−ＣＡＶＩ：１１．０，Ｌ−ＣＡＶＩ：１０．８と低下、飲用期間１０１日目Ｒ−ＣＡＶＩ：１０．９，Ｌ−ＣＡＶＩ：１０．４と低下した。ＣＡＶＩ値１０．９，１０．４は８０才以上の血管の硬さです。飲用期間１３３日目Ｒ−ＣＡＶＩ：１１．３，Ｌ−ＣＡＶＩ：１１．１と上昇、飲用期間１６４日目Ｒ−ＣＡＶＩ：１０．４，Ｌ−ＣＡＶＩ：１０．１と低下、飲用期間２０８日目Ｒ−ＣＡＶＩ：１０．６，Ｌ−ＣＡＶＩ：９．９に、飲用期間２３９日目Ｒ−ＣＡＶＩ：１０．０，Ｌ−ＣＡＶＩ：９．６と７０才代後半の血管の硬さに、更に飲用期間２７１日目Ｒ−ＣＡＶＩ：９．１５，Ｌ−ＣＡＶＩ：９．１５に低下した。ＣＡＶＩ値９．１５は７０才代後半の血管の硬さです。改善剤飲用前の急激なＣＡＶＩ値上昇の原因は、高血圧、高脂血症等のリスクファクターの動脈硬化要因は治療により正常化しており、加齢による老化現象と考えられるが、当時顔面，頚部，胸背部に皮膚炎が発症していた。（皮膚炎とＣＡＶＩ値の変動に就いての因果関係は不明）（表，図５）5) 81-year-old female. Current medical history: hypertension (blood pressure is kept normal by treatment) face, neck, chest back dermatitis. Sake (-), Tobacco (-)
The CAVI before taking the improver was measured twice, the first R-CAVI: 10.2, L-CAVI: 9.9. CAVI value 10.2 is 80 years old or older, 9.9 is the hardness of blood vessels in the late 70s. 168 days later second R-CAVI: 10.14, L-CAVI: 10.65. CAVI values 11.4 and 10.65 are the hardness of blood vessels over 80 years old. 20 days after starting the second measurement, started taking the improver. After drinking for 33 days, R-CAVI: 12.1, L-CAVI: 11.3 and the highest value in the hardness of blood vessels over 80 years old. Drinking period 63 days R-CAVI: 11.0, L-CAVI: 10.8 decreased, drinking period 101 days R-CAVI: 10.9, L-CAVI: 10.4. CAVI values 10.9 and 10.4 are the hardness of blood vessels over 80 years old. Drinking period 133 days R-CAVI: 11.3, L-CAVI: 11.1 increased, drinking period 164 days R-CAVI: 10.4, L-CAVI: 10.1 decreased, drinking period 208 days Eyes R-CAVI: 10.6, L-CAVI: 9.9, drinking period 239 days R-CAVI: 10.0, L-CAVI: 9.6 and the hardness of blood vessels in the late 70s, Furthermore, it decreased to R-CAVI: 9.15 and L-CAVI: 9.15 on the 271nd day of the drinking period. CAVI value 9.15 is the hardness of blood vessels in the late 70s. The cause of the rapid increase in CAVI before drinking the improver is considered to be an aging phenomenon due to aging because the arteriosclerosis factors of risk factors such as hypertension and hyperlipidemia have been normalized by treatment, but at that time face, neck Dermatitis had developed on the chest back. (The causal relationship between changes in dermatitis and CAVI values is unknown) (Table, Fig. 5)
６） 男性８２才 現病歴：気管支喘息、アレルギー性鼻炎、治療により症状殆どなし．酒時々１〜２合、煙草４３才より禁煙
改善剤飲用前ＣＡＶＩを２回測定し１回目Ｒ−ＣＡＶＩ：１０．２，Ｌ−ＣＡＶＩ：１０．６、７日後２回目Ｒ−ＣＡＶＩ：１０．５５、Ｌ−ＣＡＶＩ：１０．４。２回目ＣＡＶＩ測定翌日より改善剤１日１回４ｍｌを食後に１７日間飲用後３回目ＣＡＶＩ測定Ｒ−ＣＡＶＩ：１０．３，Ｌ−ＣＡＶＩ：１０．２と変化はない。１，２，３回測定のＣＡＶＩ値はすべて８０才以上の血管の硬さです。６８日間４ｍｌ飲用後４回目のＣＡＶＩ値はＲ−ＣＡＶＩ：９．９５，Ｌ−ＣＡＶＩ：９．７５と軽度の低下を示した。ＣＡＶＩ値９．９５は８０才以上の血管の硬さで，９．７５は７０才代後半の血管の硬さです。４回目ＣＡＶＩ測定より３日後改善剤１日１０ｍｌ朝夕食後２回の飲用開始、８８日飲用後Ｒ−ＣＡＶＩ：９．０，Ｌ−ＣＡＶＩ：９．１５と低下。ＣＡＶＩ値９．０は６０才代後半，９．１５は７０才代前半の血管の硬さです。飲用期間１２８日でＲ−ＣＡＶＩ：９．３５、Ｌ−ＣＡＶＩ：９．８５と上昇。飲用期間約１６５日後Ｒ−ＣＡＶＩ：９．２，Ｌ−ＣＡＶＩ：９．１と再度低下。ＣＡＶＩ値９．２，９．１は７０才代前半の血管の硬さです。飲用期間２００日後Ｒ−ＣＡＶＩ：９．９５，Ｌ−ＣＡＶＩ：１０．０に上昇、飲用期間２３５日後Ｒ−ＣＡＶＩ：９．８，Ｌ−ＣＡＶＩ：９．８５になり、飲用期間２９０日目Ｒ−ＣＡＶＩ：１０．１，Ｌ−ＣＡＶＩ：１０．２と上昇、飲用期間３１９日目Ｒ−ＣＡＶＩ：９．８，Ｌ−ＣＡＶＩ：１０．０に、飲用期間３４７日目Ｒ−ＣＡＶＩ：９．６５，Ｌ−ＣＡＶＩ：９．７５に低下。これは７０代後半の血管の硬さです。飲用期間３８２日目Ｒ−ＣＡＶＩ：９．２５，Ｌ−ＣＡＶＩ：９．７になり、飲用期間４１７日目Ｒ−ＣＡＶＩ：９．１，Ｌ−ＣＡＶＩ：９．４に低下した。ＣＡＶＩ値９．１，９．４は７０才代前半の血管の硬さです。ＣＡＶＩ測定始め頃より血圧やや高め、高い時血圧１５０〜９０位になり，改善剤飲用３４８日目より血圧降下剤カルデルサルタン シレキセチル２ｍｇ／日服用した。（有意差検定に於いて改善剤投与後のＣＡＶＩ値は血圧降下剤服用前日のＣＡＶＩ値で計算した。「図１２，１３」）（表，図６）6) Male 82 years old Current medical history: bronchial asthma, allergic rhinitis, almost no symptoms due to treatment. Liquor from 1 to 2 times, smoking cessation from cigarette 43 years old CAVI before drinking improver was measured twice, 1st R-CAVI: 10.2, L-CAVI: 10.6, 7 days later R-CAVI: 10. 55, L-CAVI: 10.4 From the day after the second CAVI measurement, 4 ml of the improving agent once a day was taken for 17 days after meal, and the third CAVI measurement R-CAVI: 10.3, L-CAVI: 10.2. There is no change. The CAVI values of 1, 2, and 3 measurements are all the hardness of blood vessels over 80 years old. The CAVI values at the 4th time after drinking 4 ml for 68 days were slightly decreased as R-CAVI: 9.95 and L-CAVI: 9.75. CAVI value 9.95 is the hardness of blood vessels over 80 years old, and 9.75 is the hardness of blood vessels in the late 70s. From the 4th CAVI measurement, 3 days later, the improver started to drink twice a day after 10 ml morning dinner, and decreased to R-CAVI: 9.0 and L-CAVI: 9.15 after drinking 88 days. CAVI value 9.0 is the hardness of blood vessels in the late 60s and 9.15 is the blood vessels in the early 70s. It increased with R-CAVI: 9.35 and L-CAVI: 9.85 in the drinking period of 128 days. About 165 days after the drinking period, R-CAVI: 9.2 and L-CAVI: 9.1 again decreased. CAVI values 9.2 and 9.1 are the hardness of blood vessels in the early 70s. After 200 days of drinking, R-CAVI increased to 9.95, L-CAVI: 10.0, and after 235 days of drinking, R-CAVI: 9.8, L-CAVI: 9.85, drinking period 290 days R -CAVI: 10.1, L-CAVI: 10.2 increased, drinking period 319 days R-CAVI: 9.8, L-CAVI: 10.0, drinking period 347 days R-CAVI: 9. 65, L-CAVI: Decrease to 9.75. This is the hardness of blood vessels in the late 70s. Drinking period 382 days R-CAVI: 9.25, L-CAVI: 9.7, drinking period 417 days R-CAVI: 9.1, L-CAVI: 9.4. CAVI values 9.1 and 9.4 are the blood vessel hardness in the early 70s. The blood pressure was slightly elevated from the beginning of the CAVI measurement, and the blood pressure was 150 to 90 when the blood pressure was high. From the 348th day of taking the improving agent, the blood pressure lowering agent, caldersartan cilexetil was taken at 2 mg / day. (In the significant difference test, the CAVI value after administration of the improving agent was calculated by the CAVI value on the day before taking the antihypertensive agent. “FIGS. 12 and 13”) (Table, FIG. 6)
７） 女性７８才 既往症：直腸癌（７６才）全治．現病歴：気管支喘息、心不全、心房細動．酒（−）、煙草１５〜２０本、３年前より禁煙
改善剤飲用前ＣＡＶＩを３回測定し１回目、Ｒ−ＣＡＶＩ：８．５，Ｌ−ＣＡＶＩ：９．０。ＣＡＶＩ値８．５は６０才代後半、９．０は７０才代後半の血管の硬さです。１６１日後２回目Ｒ−ＣＡＶＩ：８．６，Ｌ−ＣＡＶＩ：８．７、ＣＡＶＩ値８．６は７０才代前半、８．７は７０才代後半の血管の硬さです。２５２日後３回目Ｒ−ＣＡＶＩ：９．３，Ｌ−ＣＡＶＩ：９．３です。ＣＡＶＩ値９．３は７０才代後半の血管の硬さです。３回目測定より４２日目改善剤飲用開始、１４日飲用後Ｒ−ＣＡＶＩ：８．０，Ｌ−ＣＡＶＩ：７．８５に低下。ＣＡＶＩ値８．０は６０才代後半、７．８５は６０才代前半の血管の硬さです。飲用期間６３日目Ｒ−ＣＡＶＩ：８．１，Ｌ−ＣＡＶＩ：８．３に、飲用期間１１２日目Ｒ−ＣＡＶＩ：８．０，Ｌ−ＣＡＶ：８．２５に、飲用期間１５３日目Ｒ−ＣＡＶＩ：８．３，Ｌ−ＣＡＶ８．２５に上昇。飲用期間２１６日目Ｒ−ＣＡＶＩ：８．１，Ｌ−ＣＡＶ：８．０５に、飲用期間２７２日目Ｒ−ＣＡＶＩ：７．３，Ｌ−ＣＡＶ７．４に低下した。ＣＡＶＩ値７．３，７．４は５０才代前半の血管の硬さです。（表，図７）7) Female 78 years old History: Rectal cancer (76 years old) Complete cure. Current medical history: bronchial asthma, heart failure, atrial fibrillation. Sake (-), 15 to 20 cigarettes, quit smoking from 3 years ago CAVI before drinking improver was measured 3 times, R-CAVI: 8.5, L-CAVI: 9.0. CAVI value 8.5 is the hardness of blood vessels in the late 60s and 9.0 is the hardness of blood vessels in the late 70s. 161 days later R-CAVI: 8.6, L-CAVI: 8.7, CAVI value 8.6 is the hardness of blood vessels in the early 70s and 8.7 is the hardness of blood vessels in the late 70s. 252 days later the third R-CAVI: 9.3 and L-CAVI: 9.3. CAVI value 9.3 is the hardness of blood vessels in the late 70s. From the 3rd measurement, on the 42nd day, drinking of the improving agent was started, and after 14 days of drinking, R-CAVI: 8.0 and L-CAVI: 7.85. CAVI value 8.0 is the hardness of blood vessels in the late 60s and 7.85 is the hardness of blood vessels in the early 60s. Drinking period 63 days R-CAVI: 8.1, L-CAVI: 8.3, drinking period 112 days R-CAVI: 8.0, L-CAV: 8.25, drinking period 153 days R -CAVI: Increased to 8.3, L-CAV 8.25. Drinking period 216 days R-CAVI: 8.1, L-CAV: 8.05, drinking period 272 days R-CAVI: 7.3, L-CAV 7.4. CAVI values 7.3 and 7.4 are the hardness of blood vessels in the early 50s. (Table, Fig. 7)
８） 女性７６才 現病歴：鬱病．酒（−）、煙草（−）
改善剤飲用前３回ＣＡＶＩを測定し，１回目Ｒ−ＣＡＶＩ：８．８，Ｌ−ＣＡＶＩ：８．６。ＣＡＶＩ値８．８，８．６は７０才代前半の血管の硬さです。１６０日後２回目Ｒ−ＣＡＶＩ：９．５５，Ｌ−ＣＡＶＩ：９．１５。ＣＡＶＩ値９．５５，９．１５は７０才代後半の血管の硬さです。２３７日後３回目Ｒ−ＣＡＶＩ：９．０，Ｌ−ＣＡＶＩ：８．８に、ＣＡＶＩ値９．０は７０才代後半、８．８は７０才代前半の血管の硬さです。３回目測定日より改善剤飲用開始、４２日飲用後Ｒ−ＣＡＶＩ：９．２５，Ｌ−ＣＡＶＩ：８．８５、飲用期間８４日目膀胱炎になり、Ｒ−ＣＡＶＩ：９．７５，Ｌ−ＣＡＶＩ：９．３５と上昇し７０才代後半血管の硬さに、飲用期間１２２日目Ｒ−ＣＡＶＩ：９．１，Ｌ−ＣＡＶ：８．９５に、飲用期間１５７日目Ｒ−ＣＡＶＩ：９．０５，Ｌ−ＣＡＶＩ：８．６５に、飲用期間１８５日目Ｒ−ＣＡＶＩ：９．０，Ｌ−ＣＡＶＩ：８．９に、ＣＡＶＩ値９．０は７０才代後半、８．８は７０才代前半の血管の硬さです。（表，図８）8) 76-year-old woman Current medical history: depression. Sake (-), Tobacco (-)
CAVI was measured 3 times before taking the improving agent, and the first R-CAVI: 8.8, L-CAVI: 8.6. CAVI values 8.8 and 8.6 are the hardness of blood vessels in the early 70s. The second time after 160 days R-CAVI: 9.55, L-CAVI: 9.15. CAVI values of 9.55 and 9.15 are the hardness of blood vessels in the late 70s. 237 days later R-CAVI: 9.0, L-CAVI: 8.8, CAVI value 9.0 is the hardness of the blood vessels in the late 70s, 8.8 is the hardness of the blood vessels in the early 70s. From the 3rd measurement day, drinking of the improving agent was started. After drinking for 42 days, R-CAVI: 9.25, L-CAVI: 8.85, drinking period 84 days became cystitis, R-CAVI: 9.75, L- CAVI increased to 9.35, the hardness of the blood vessels in the late 70s, drinking period 122 days R-CAVI: 9.1, L-CAV: 8.95, drinking period 157 days R-CAVI: 9 .05, L-CAVI: 8.65, drinking period 185 days R-CAVI: 9.0, L-CAVI: 8.9, CAVI value 9.0 is in the late 70s, 8.8 is 70 It is the hardness of the blood vessels in the first half of their generations. (Table, Fig. 8)
９） 女性７８才 既往症：子宮体癌（７７才）．酒たまに少し、たばこ（ー）
改善剤飲用前１回ＣＡＶＩを測定、Ｒ−ＣＡＶＩ：８．９５，Ｌ−ＣＡＶＩ：９．０５。ＣＡＶＩ値８．９５、９．０５は７０才代後半の血管の硬さです。改善剤９０日飲用後２回目、Ｒ−ＣＡＶＩ：８．２，Ｌ−ＣＡＶＩ：８．５と低下。ＣＡＶＩ値８．２、８．５は７０才代前半の血管の硬さです。飲用期間１３８日目Ｒ−ＣＡＶＩ：９．０５，Ｌ−ＣＡＶＩ：９．２５に上昇。飲用期間１８７日目Ｒ−ＣＡＶＩ：７．８５，Ｌ−ＣＡＶ７．７５に低下。ＣＡＶＩ値７．８５、７．７５は６０才代前半の血管の硬さです。飲用期間２２２日目Ｒ−ＣＡＶＩ：８．７６，Ｌ−ＣＡＶ：８．５６に上昇、飲用期間２５０日目Ｒ−ＣＡＶＩ：８．６５，Ｌ−ＣＡＶ８．６に、飲用期間３０４日目Ｒ−ＣＡＶＩ：８．４，Ｌ−ＣＡＶＩ：８．３に低下。ＣＡＶＩ値８．４、８．３は７０才代前半の血管の硬さです。飲用期間３３４日目Ｒ−ＣＡＶＩ：８．７，Ｌ−ＣＡＶＩ：９．０５と上昇、ＣＡＶＩ値８．７、９．０５は７０才代後半の血管の硬さです。飲用期間３６７日目Ｒ−ＣＡＶＩ：８．７，Ｌ−ＣＡＶＩ：８．９に、飲用期間４１８日目Ｒ−ＣＡＶＩ：８．７５，Ｌ−ＣＡＶＩ：８．５５に、飲用期間４５８日目Ｒ−ＣＡＶＩ：８．４５，Ｌ−ＣＡＶＩ８．７に低下している。ＣＡＶＩ値８．４５、８．７は７０才代前半の血管の硬さです。（表，図９）9) Female 78 years old History: Endometrial cancer (77 years old). Tobacco a little, cigarette (-)
CAVI was measured once before taking the improving agent, R-CAVI: 8.95, L-CAVI: 9.05. CAVI values of 8.95 and 9.05 are the hardness of blood vessels in the late 70s. The second time after taking the improving agent for 90 days, R-CAVI: 8.2, L-CAVI: 8.5. CAVI values 8.2 and 8.5 are the hardness of blood vessels in the early 70s. Ingestion period 138 days R-CAVI: 9.05, L-CAVI: 9.25. Ingestion period 187 days R-CAVI: 7.85, L-CAV decreased to 7.75. CAVI values 7.85 and 7.75 are the hardness of blood vessels in the early 60s. Drinking period 222 days R-CAVI: 8.76, L-CAV: rise to 8.56, drinking period 250 days R-CAVI: 8.65, L-CAV8.6, drinking period 304 days R- CAVI: decreased to 8.4, L-CAVI: 8.3. CAVI values 8.4 and 8.3 are the hardness of blood vessels in the early 70s. Ingestion period 334th day R-CAVI: 8.7, L-CAVI: 9.05 and increased, CAVI values 8.7, 9.05 is the hardness of blood vessels in the late 70s. Drinking period 367 days R-CAVI: 8.7, L-CAVI: 8.9, drinking period 418 days R-CAVI: 8.75, L-CAVI: 8.55, drinking period 458 days R -CAVI: 8.45, L-CAVI 8.7. CAVI values 8.45 and 8.7 are the hardness of blood vessels in the early 70s. (Table, Fig. 9)
ＩＩ．対照として健康成人、男性１名、女性３名。高血圧症、高脂血症で血圧、脂質が治療により正常化し、安定した女性６名で動脈硬化改善剤を飲用せずＣＡＶＩを測定した。II. Healthy adults, 1 male and 3 females as controls. CAVI was measured in 6 stable women without hypertension and hyperlipidemia without taking an arteriosclerosis improving agent.
１．男性３５才 健康 酒時々１合位 煙草１日１０本位
ＣＡＶＩを４回測定し１回目Ｒ−ＣＡＶＩ：５．６，Ｌ−ＣＡＶＩ：５．８、９９日後２回目Ｒ−ＣＡＶＩ：５．７５，Ｌ−ＣＡＶＩ：５．８５、１８７日後３回目Ｒ−ＣＡＶＩ：５．７５，Ｌ−ＣＡＶＩ：５．８５に、２９９日後４回目Ｒ−ＣＡＶＩ：５．８，Ｌ−ＣＡＶＩ：５．７と安定。ＣＡＶＩ値は左右共２０才代前半の血管の硬さに相当し，安定している。（表１０，図１０の１，対照Ｉの１）1. Male 35 years old Health Liquor occasionally 1 position Cigarette 10 times a day CAVI was measured 4 times, 1st R-CAVI: 5.6, L-CAVI: 5.8, 99 days later 2nd R-CAVI: 5.75, L-CAVI: 5.85, 3rd time after 187 days R-CAVI: 5.75, L-CAVI: 5.85, 4th time after 299 days R-CAVI: 5.8, L-CAVI: 5.7, stable . The CAVI value corresponds to the hardness of blood vessels in the early 20s on both the left and right sides and is stable. (Table 10, Fig. 10, 1 of Control I)
２．女性５７才 健康 酒（−） 煙草（−）
ＣＡＶＩを４回測定し１回目Ｒ−ＣＡＶＩ：８．１５，Ｌ−ＣＡＶＩ：７．９．１７５日後２回目Ｒ−ＣＡＶＩ：７．８５，Ｌ−ＣＡＶＩ：７．５、２９３日後３回目Ｒ−ＣＡＶＩ：７．７５，Ｌ−ＣＡＶＩ：７．５５、３６７日後４回目Ｒ−ＣＡＶＩ：７．９，Ｌ−ＣＡＶＩ：７．８と安定。ＣＡＶＩ値は左右共５０才代前半か後半の血管の硬さに相当し，安定している。（表１１，図１０の２，対照Ｉの２）2. Female 57 years old Healthy Sake (-) Tobacco (-)
CAVI was measured 4 times, 1st R-CAVI: 8.15, L-CAVI: 7.9.175 days later 2nd R-CAVI: 7.85, L-CAVI: 7.5, 293 days later 3rd R- CAVI: 7.75, L-CAVI: 7.55, stable after 367 days, 4th R-CAVI: 7.9, L-CAVI: 7.8. The CAVI value corresponds to the hardness of blood vessels in the first half or late half of the left and right, and is stable. (Table 11, FIG. 10, 2 of Control I)
３．女性４２才 健康 酒（−） 煙草（−）
ＣＡＶＩを５回測定し１回目Ｒ−ＣＡＶＩ：６．６，Ｌ−ＣＡＶＩ：６．６５、６３日後２回目Ｒ−ＣＡＶＩ：６．６，Ｌ−ＣＡＶＩ：６．４４、１１９日後３回目Ｒ−ＣＡＶＩ：６．７５，Ｌ−ＣＡＶＩ：６．６５、１９５日後４回目Ｒ−ＣＡＶＩ：６．７，Ｌ−ＣＡＶＩ：６．６に、２７２日後５回目Ｒ−ＣＡＶＩ：６．５，Ｌ−ＣＡＶＩ：６．３と安定。ＣＡＶＩ値は左右共３０才代後半か、４０才代前半の血管の硬さに相当し，安定している。（表１２，図１０の３，対照Ｉの３）3. Female 42 years old Healthy Sake (-) Tobacco (-)
CAVI was measured 5 times, 1st R-CAVI: 6.6, L-CAVI: 6.65, 63 days later 2nd R-CAVI: 6.6, L-CAVI: 6.44, 119 days later 3rd R- CAVI: 6.75, L-CAVI: 6.65, 195 days after 4th R-CAVI: 6.7, L-CAVI: 6.6, 272 days after 5th R-CAVI: 6.5, L-CAVI : Stable with 6.3. The CAVI value corresponds to the hardness of blood vessels in the late 30s or early 40s, and is stable. (Table 12, FIG. 10, 3 of control I)
４．女性３８才 健康 酒（−） 煙草（−）
ＣＡＶＩを３回測定し１回目Ｒ−ＣＡＶＩ：５．９，Ｌ−ＣＡＶＩ：６．０、６４日後２回目Ｒ−ＣＡＶＩ：５．９，Ｌ−ＣＡＶＩ：５．９、１４３日後３回目Ｒ−ＣＡＶＩ：５．６、Ｌ−ＣＡＶＩ：５．６５と安定。ＣＡＶＩ値は左右共２０才代未満か、２０才代前半の血管の硬さに相当し，安定している。
（表１３，図１０の４，対照Ｉの４）4). Female 38 years old Healthy Sake (-) Tobacco (-)
CAVI was measured 3 times, 1st R-CAVI: 5.9, L-CAVI: 6.0, 64 days later 2nd R-CAVI: 5.9, L-CAVI: 5.9, 143 days later 3rd R- Stable with CAVI: 5.6 and L-CAVI: 5.65. The CAVI value corresponds to the hardness of blood vessels in the left and right in the 20s or early 20s, and is stable.
(Table 13, FIG. 10, 4, control I 4)
５．女性７４才 高血圧、高脂血漿：治療により正常値維持 酒（−）煙草（−）
ＣＡＶＩを４回測定し１回目、Ｒ−ＣＡＶＩ：８．４，Ｌ−ＣＡＶＩ：８．６、１４９日後２回目Ｒ−ＣＡＶＩ：８．２，Ｌ−ＣＡＶＩ：８．２５、２８９日後３回目Ｒ−ＣＡＶＩ：８．２５，Ｌ−ＣＡＶＩ：８．４５、４５０日後４回目Ｒ−ＣＡＶＩ：８．１，Ｌ−ＣＡＶＩ：８．５と安定。ＣＡＶＩ値は左右共６０才代後半か、７０才代前半の血管の硬さに相当し，安定している。（表１４，図１１の１，対照ＩＩの１）5. 74-year-old woman High blood pressure, high-fat plasma: normal level maintained by treatment Sake (-) Tobacco (-)
CAVI was measured 4 times, 1st time, R-CAVI: 8.4, L-CAVI: 8.6, 149 days later 2nd R-CAVI: 8.2, L-CAVI: 8.25, 289 days later 3rd time R -Stable with CAVI: 8.25, L-CAVI: 8.45, 4th time after 450 days R-CAVI: 8.1, L-CAVI: 8.5. The CAVI value corresponds to the hardness of blood vessels in the late 60s or early 70s, and is stable. (Table 14, FIG. 11, 1 of Control II)
６．女性７３才 高血圧、高脂血漿：治療により正常値維持 酒（−）煙草（−）
ＣＡＶＩを４回測定し１回目Ｒ−ＣＡＶＩ：９．０５，Ｌ−ＣＡＶＩ：８．９５、１６１日後２回目Ｒ−ＣＡＶＩ：９．４５，Ｌ−ＣＡＶＩ：９．３、２６８日後３回目Ｒ−ＣＡＶＩ：８．８５，Ｌ−ＣＡＶＩ：９．１、３８３日後４回目Ｒ−ＣＡＶＩ：９．２，Ｌ−ＣＡＶＩ：９．４と安定。ＣＡＶＩ値は左右共７０才代前半の血管の硬さに相当し，安定している。（表１５，図１１の２，対照ＩＩの２）6). Female 73 years old Hypertension, high-fat plasma: normal level maintained by treatment Sake (-) Tobacco (-)
CAVI was measured 4 times, 1st R-CAVI: 9.05, L-CAVI: 8.95, 2nd time after 161 days R-CAVI: 9.45, L-CAVI: 9.3, 3rd time after 268 days R-CAVI Stable with CAVI: 8.85, L-CAVI: 9.1, 4th time after 383 days R-CAVI: 9.2, L-CAVI: 9.4. The CAVI value corresponds to the hardness of blood vessels in the early 70s on both the left and right sides and is stable. (Table 15, FIG. 11, 2, Control II-2)
７．女性８０才 高血圧、高脂血漿：治療により正常値維持 酒（−）煙草（−）
ＣＡＶＩを５回測定し１回目Ｒ−ＣＡＶＩ：１０．４５，Ｌ−ＣＡＶＩ：１０．３５、１３２日後２回目Ｒ−ＣＡＶＩ：１０．３，Ｌ−ＣＡＶＩ：１０．１、２２４日後３回目Ｒ−ＣＡＶＩ：１０．３，Ｌ−ＣＡＶＩ：１０．３、３２４日後４回目Ｒ−ＣＡＶＩ：１０．５，Ｌ−ＣＡＶＩ：１０．５、４１８日後５回目Ｒ−ＣＡＶＩ：１０．２５，Ｌ−ＣＡＶＩ：１０．０５と安定。血管の硬さは左右共８０才以上の硬さ、左右のＣＡＶＩ値は１０．０５から１０．５の間で安定している。（表１６，図１１の３，対照ＩＩの３）7). 80-year-old woman High blood pressure, high-fat plasma: normal level maintained by treatment Sake (-) Tobacco (-)
CAVI was measured 5 times, 1st R-CAVI: 10.45, L-CAVI: 10.35, 132 days after 2nd R-CAVI: 10.3, L-CAVI: 10.1, 224 days after 3rd R- CAVI: 10.3, L-CAVI: 10.3, 324 days after 4th R-CAVI: 10.5, L-CAVI: 10.5, 418 days after 5th R-CAVI: 10.25, L-CAVI: Stable at 10.05. The blood vessel hardness is 80 years or older on both sides, and the left and right CAVI values are stable between 10.05 and 10.5. (Table 16, FIG. 11, 3, control II-3)
８．女性６８才 高血圧、高脂血漿、糖尿病：治療により正常値維持 酒（−）煙草（−）
ＣＡＶＩを４回測定し１回目Ｒ−ＣＡＶＩ：８．５５，Ｌ−ＣＡＶＩ：８．６５、８０日後２回目Ｒ−ＣＡＶＩ：８．３５，Ｌ−ＣＡＶＩ：８．７、１６８日後３回目Ｒ−ＣＡＶＩ：８．３５，Ｌ−ＣＡＶＩ：８．７、３２３日後４回目Ｒ−ＣＡＶＩ：８．６，Ｌ−ＣＡＶＩ：８．５５と安定。ＣＡＶＩ値は左右共６０才代後半の硬さに相当し，安定している。（表１７，図１１の４，対照ＩＩの４）。8). 68-year-old female High blood pressure, high-fat plasma, diabetes: normal level maintained by treatment Alcohol (-) Tobacco (-)
CAVI was measured 4 times, 1st R-CAVI: 8.55, L-CAVI: 8.65, 2nd R-CAVI: 8.35 after 80 days, L-CAVI: 8.7, 3rd R-CAVI after 168 days CAVI: 8.35, L-CAVI: 8.7, 323 days later, 4th time R-CAVI: 8.6, L-CAVI: 8.55, stable. The CAVI value corresponds to the hardness in the late 60s and is stable. (Table 17, FIG. 11, 4, control II-4).
９． 女性７４才 高血圧、高脂血漿：治療により正常値維持 酒（−）煙草（−）
ＣＡＶＩを５回測定し１回目、Ｒ−ＣＡＶＩ：１０．１５，Ｌ−ＣＡＶＩ：１０．１、１１９日後２回目Ｒ−ＣＡＶＩ：１０．０，Ｌ−ＣＡＶＩ：１０．１、２０４日後３回目Ｒ−ＣＡＶＩ：９．７５，Ｌ−ＣＡＶＩ：１０．０、２８２日後４回目Ｒ−ＣＡＶＩ：９．５５，Ｌ−ＣＡＶＩ：９．５５、４２２日後５回目Ｒ−ＣＡＶＩ：９．８５，Ｌ−ＣＡＶＩ：９．８５と安定。ＣＡＶＩ値は左右共７０才代後半の硬さに相当し，安定している。（表１８，図１１の５，対照ＩＩの５）。9. 74-year-old woman High blood pressure, high-fat plasma: normal level maintained by treatment Sake (-) Tobacco (-)
CAVI was measured 5 times, 1st time, R-CAVI: 10.15, L-CAVI: 10.1, 119 days later 2nd R-CAVI: 10.0, L-CAVI: 10.1, 204 days 3rd time R -CAVI: 9.75, L-CAVI: 10.0, 4th time after 282 days R-CAVI: 9.55, L-CAVI: 9.55, 5th time after 422 days R-CAVI: 9.85, L-CAVI : Stable at 9.85. The CAVI value corresponds to the hardness in the late 70s, and is stable. (Table 18, FIG. 11, 5 of control II).
１０．女性４９才 高血圧、高脂血漿：治療により正常値維持 酒（−）煙草（−）
ＣＡＶＩを６回測定し１回目Ｒ−ＣＡＶＩ：６．５５，Ｌ−ＣＡＶＩ：６．４、８８日後２回目Ｒ−ＣＡＶＩ：６．７，Ｌ−ＣＡＶＩ：６．８、１８６日後３回目Ｒ−ＣＡＶＩ：６．９５，Ｌ−ＣＡＶＩ：７．０５、２７５日後４回目Ｒ−ＣＡＶＩ：６．９，Ｌ−ＣＡＶＩ：６．７、３２２日後５回目Ｒ−ＣＡＶＩ：６．６，Ｌ−ＣＡＶＩ：６．４、３９０日目６回目Ｒ−ＣＡＶＩ：６．８５，Ｌ−ＣＡＶＩ：６．７５と安定。ＣＡＶＩ値は左右４０才代前半，後半の硬さに相当し，安定している。（表１９，図１１の６，対照ＩＩの６）。10. 49-year-old woman High blood pressure, high-fat plasma: normal level maintained by treatment Sake (-) Tobacco (-)
CAVI was measured 6 times, 1st R-CAVI: 6.55, L-CAVI: 6.4, 2nd time after 88 days R-CAVI: 6.7, L-CAVI: 6.8, 3rd time after 186 days R-CAVI CAVI: 6.95, L-CAVI: 7.05, 4th time after 275 days R-CAVI: 6.9, L-CAVI: 6.7, 5th time after 322 days R-CAVI: 6.6, L-CAVI: Stable at 6.4, 390th day 6th R-CAVI: 6.85, L-CAVI: 6.75. The CAVI value is equivalent to the hardness of the left and right 40s and is stable. (Table 19, FIG. 11, 6, control II-6).
ＩＶ．結果
９例中１，２，４，５，６，７の症例は動脈硬化改善剤の飲用によりＣＡＶＩ値の低下、すなわち動脈硬化改善の効果を示しています。３の症例は飲用当初ＣＡＶＩ値の低下を認めましたが、飲用しない期間もあり、更に検討が必要です。８の症例はＣＡＶＩ値低下を認めませんが、全体としてＣＡＶＩ値の増加も認めません。９の症例は飲用当初ＣＡＶＩ値の低下を認めましたが、軽度の高脂血症のためＣＡＶＩ値は変動していますが、全体としてＣＡＶＩ値の増加傾向はなく、軽度の低下傾向を認めます。以上９例中６例にＣＡＶＩ値の低下，すなわち動脈硬化改善剤が動脈内皮に作用し動脈硬化改善に効果がある事を示しており、更に
症例１ 女性 ６２才 既往症： 低色素性貧血 全治、現病歴：なし、酒（−）、たばこ（−）
ＣＡＶＩ値は動脈硬化改善剤飲用前 １回目 Ｒ−ＣＡＶＩ ７．５，Ｌ−ＣＡＶＩ ７．５ ２回目 Ｒ−ＣＡＶＩ ７．２，Ｌ−ＣＡＶＩ ７．８で５０才代後半の血管の硬さより動脈硬化改善剤飲用４１１日目のＣＡＶＩ値はＲ−ＣＡＶＩ ６．４５，Ｌ−ＣＡＶＩ ６．５と３０才代前半に相当する血管の硬さに低下した。
症例２ 女性 ４９才 既往症；低色素性貧血、酒時々１合位、煙草（−）
ＣＡＶＩ値は動脈硬化改善剤飲用前 １回目 Ｒ−ＣＡＶＩ ７．０，Ｌ−ＣＡＶＩ ７．２、４７日後 ２回目 Ｒ−ＣＡＶＩ ７．１５，Ｌ−ＣＡＶＩ ７．１５で、ＣＡＶＩ値７．０は年令４０才代前半の血管の硬さ、ＣＡＶＩ値７．１５、７．２は年令４０才代後半の血管の硬さです。動脈硬化改善剤飲用３２６日目のＣＡＶＩ値はＲ−ＣＡＶＩ ６．７ Ｌ−ＣＡＶＩ ６．７と４０才代前半に相当する血管の硬さに低下した。
症例６ 男性 ８２才 現病歴；気管支喘息、アレルギー性鼻炎、治療により症状ほとんどなし。酒時々１〜２合、煙草４３才より禁煙。
ＣＡＶＩ値は動脈硬化改善剤飲用前 １回目 Ｒ−ＣＡＶＩ １０．２、Ｌ−ＣＡＶＩ １０．６、７日後 ２回目 Ｒ−ＣＡＶＩ １０．５５，Ｌ−ＣＡＶＩ １０．４で、ＣＡＶＩ値１０．２以上の値は年令８０才 以上の血管の硬さです。動脈硬化改善剤飲用３４７日目（血圧降下剤服用前日）のＣＡＶＩ値はＲ−ＣＡＶＩ ９．６５、Ｌ−ＣＡＶＩ ９．７５と７０才代後半に相当する血管の硬さに低下した。
以上の様に種々のリスクファクター（糖尿病、高血圧、高脂血漿、高尿酸血漿、喫煙、肥満、ストレス、運動不足、アルコールの過剰摂取）の無い１、２、６の症例は、動脈硬化改善剤の飲用によりＣＡＶＩ値の低下を認め、加齢に基づく生理的な動脈硬化を改善する効果のある動脈硬化改善剤であることを示しています。（但し６の症例は血圧降下剤服用前日のＣＡＶＩ値まで）
又８，９の２例は全体としてＣＡＶＩ値の増加はなく動脈硬化の進行が無い事を示しています。又対象１の健康成人４名動脈硬化改善剤飲用せずＣＡＶＩ値測定、測定期間中ＣＡＶＩ値の変動巾０．４以下。測定初回と最終回測定のＣＡＶＩ値の変動巾は０．３５以下で改善剤飲用例に比べ変動巾は小さい。対象２の高血圧、高脂血症患者６名、治療により血圧、脂質の安定した成人６名改善剤服用せずＣＡＶＩ値測定、測定期間中ＣＡＶＩ値の変動巾０．６５以下。測定初回と最終回測定のＣＡＶＩ値の変動巾は０．４５以下で改善剤飲用例に比べ変動巾は小さい。更に有意差検定において９名の動脈硬化改善剤飲用者の飲用前と飲用後のＣＡＶＩ値の変動は対照者（改善剤非飲用者）に比べ左右共動脈硬化改善効果の有意差を認めています。（図，表１２，１３）更にこの効果は直接いのちに関係のある微小循環（毛細血管，毛細淋巴管）にも好影響を及ぼし，寿命の延長に寄与するものと確信します。IV. Results Of the 9 cases, 1, 2, 4, 5, 6 and 7 cases show a decrease in CAVI value due to the use of an arteriosclerosis improving agent, that is, an effect of improving arteriosclerosis. Three cases showed a decrease in CAVI levels at the beginning of drinking, but there are periods when they are not taken and further investigation is required. Eight cases do not show a decrease in CAVI levels, but overall no increase in CAVI levels. Nine cases showed a decrease in the CAVI value at the beginning of drinking, but the CAVI value fluctuated due to mild hyperlipidemia, but overall there was no increase in the CAVI value and a slight decrease was observed. . 6 of 9 cases show a decrease in CAVI value, that is, an arteriosclerosis improving agent acts on the arterial endothelium and is effective in improving arteriosclerosis. Case 1 Female 62 years Past history: Hypochromic anemia Current medical history: none, sake (-), tobacco (-)
CAVI values are 1st R-CAVI 7.5, L-CAVI 7.5 2nd R-CAVI 7.2, L-CAVI 7.8 before taking the arteriosclerosis improving agent. The CAVI value on the 411st day when the sclerosing agent was taken decreased to R-CAVI 6.45, L-CAVI 6.5, and blood vessel hardness corresponding to the early 30s.
Case 2 Female 49 years old History; Hypochromic anemia, Liquor occasionally 1 position, Tobacco (-)
The CAVI values are the first R-CAVI 7.0, L-CAVI 7.2, 47 days after taking the arteriosclerosis improving agent, and the second R-CAVI 7.15, L-CAVI 7.15. Blood vessel hardness in the early 40s, CAVI values 7.15 and 7.2 are the blood vessel hardness in the late 40s. The CAVI value on the 326th day after taking the arteriosclerosis improving agent decreased to R-CAVI 6.7 L-CAVI 6.7, and the hardness of the blood vessel corresponding to the early 40s.
Case 6 Male 82 years old Current medical history; bronchial asthma, allergic rhinitis, almost no symptoms due to treatment. Smokers sometimes quit smoking from 1 to 2 cigarettes 43 years old.
CAVI values are 1st R-CAVI 10.2, L-CAVI 10.6, 7 days after taking the arteriosclerosis improving agent R-CAVI 10.55, L-CAVI 10.4, CAVI value 10.2 or more The value of is the hardness of blood vessels over 80 years of age. The CAVI value on the 347th day (the day before taking the antihypertensive agent) after taking the arteriosclerosis improving agent decreased to R-CAVI 9.65, L-CAVI 9.75, and blood vessel hardness corresponding to the late 70s.
As described above, cases of 1, 2 and 6 without various risk factors (diabetes, hypertension, high fat plasma, high uric acid plasma, smoking, obesity, stress, lack of exercise, alcohol overdose) It is shown that it is an arteriosclerosis improving agent that has an effect of improving physiological arteriosclerosis based on aging due to a decrease in CAVI value due to drinking. (However, in 6 cases, up to the CAVI value the day before taking the antihypertensive agent)
In addition, two cases of 8 and 9 show that there is no increase in CAVI value as a whole and there is no progression of arteriosclerosis. In addition, 4 healthy adults of subject 1 did not take an arteriosclerosis improving agent, measured CAVI value, and fluctuation range of CAVI value was 0.4 or less during measurement period. The variation range of the CAVI value in the first measurement and the final measurement is 0.35 or less, and the variation range is smaller than in the case of taking the improver. 6 subjects with hypertension and hyperlipidemia of subject 2, 6 adults with stable blood pressure and lipids treated, CAVI value measurement without taking the improving agent, CAVI value fluctuation range of 0.65 or less during the measurement period. The variation range of the CAVI value in the first measurement and the final measurement is 0.45 or less, and the variation range is smaller than in the case of taking the improver. Furthermore, in the significant difference test, the change in the CAVI value before and after drinking of 9 arteriosclerosis improvers was significantly different from that of the control (no improver) . (Figures, Tables 12 and 13) Furthermore, this effect has a positive effect on the microcirculation (capillaries and capillaries) that are directly related to life, and we are convinced that it contributes to the extension of life.
本発明において使用されるコエンザイムＱ１０は補酵素として生物活性を有し、ミトコンドリアの電子伝達系の構成成分で、ＡＴＰの生合成賦活成分としてエネルギーを生み出す働きがある。コエンザイムＱ１０はユビキノン類（２．３−ジメトキシー５−メチルー６ポリプレニルー１、４ベンゾキノン）の側鎖のイソプレン単位が１０である人特有のユビキノン類であり、ユビデカレノン又は補酵素ＵＱ１０とも呼ばれている。分子量は８６３．３６で、融点が約４８度の黄色から橙黄色の結晶性の粉末で、匂い及び味はない。エーテルに溶けやすく、光によって分解し、着色が強くなる。コエンザイムＱ１０の添加量としては特に制限されることはないが、好ましくは０．１〜２．０重量％、より好ましくは０．３〜１．０重量％である。これ以上の濃度では動脈内皮への好影響が向上することが期待できず、又これ以下の濃度では動脈内皮への好影響が期待されない。 Coenzyme Q10 used in the present invention has biological activity as a coenzyme, is a component of the mitochondrial electron transport system, and has a function of generating energy as a component for activating ATP biosynthesis. Coenzyme Q10 is a ubiquinone peculiar to humans whose isoprene unit in the side chain of ubiquinones (2.3-dimethoxy-5-methyl-6polyprenyl-1,4benzoquinone) is 10, and is also called ubidecalenone or coenzyme UQ10. It is a yellow to orange-yellow crystalline powder having a molecular weight of 863.36 and a melting point of about 48 degrees, and has no smell or taste. Easily soluble in ether, decomposes by light and becomes more colored. The amount of coenzyme Q10 added is not particularly limited, but is preferably 0.1 to 2.0% by weight, more preferably 0.3 to 1.0% by weight. A concentration higher than this cannot be expected to improve the positive effect on the arterial endothelium, and a concentration lower than this cannot be expected to have a positive effect on the arterial endothelium.
本発明において使用されるシステインは、生体内代謝系において、ＳＨ供与体としての役割を果たし、ＳＨ酵素の賦活剤として作用する。皮膚代謝の正常化、抗アレルギー、解毒作用がある。システインもしくはその誘導体としても特に限定されるものではないが、Ｌ−システインの誘導体としては、Ｎ−アセチルーＬ−システイン、Ｌ−ホモシステイン、Ｌ−システイン酸、Ｌ−ホモシステイン酸、Ｌ−システインスルフィン酸、Ｓ−スルフイノーＬ−システイン、Ｓ−スルホーＬ−システイン、シスチンなどを挙げる事が出来る。又Ｌ−システインおよびその誘導体の塩としては、塩酸塩、硝酸塩、硫酸塩等の鉱酸塩、ナトリウム塩、カリウム塩、カルシウム塩、マグネシウム塩などのアルカリ金属塩、アルカリ土類金属塩を挙げることが出来る。本発明において、Ｌ−システイン、その誘導体またはそれらの塩としてはＬ−システインが好ましい。 Cysteine used in the present invention plays a role as an SH donor in the in vivo metabolic system and acts as an activator of SH enzyme. Has normal skin metabolism, anti-allergy and detoxification. Cysteine or its derivative is not particularly limited, but examples of L-cysteine derivatives include N-acetyl-L-cysteine, L-homocysteine, L-cysteic acid, L-homocysteic acid, L-cysteine sulfin. Examples thereof include acids, S-sulfinol L-cysteine, S-sulfo L-cysteine, and cystine. Examples of salts of L-cysteine and derivatives thereof include mineral salts such as hydrochloride, nitrate and sulfate, alkali metal salts such as sodium salt, potassium salt, calcium salt and magnesium salt, and alkaline earth metal salts. I can do it. In the present invention, L-cysteine is preferred as L-cysteine, a derivative thereof or a salt thereof.
本発明において使用されるビタミンＡは網膜の暗順応を高める作用、皮膚、粘膜の異常乾燥、角化を改善し、疾病に対する抵抗力を増す作用がある。ビタミンＡ類としては特に限定されるものではないが、その具体例として、レチノール、デヒドロレチノール、酢酸レチノ−ル、パルミチン酸レチノールもしくはこれらの誘導体等が挙げられ、レチノールの類縁化合物であるレチノイドとしてはレチナール、レチニールエステル、レチノイン酸等の誘導体が挙げられる。本発明において、レチノール、その誘導体としてはパルミチン酸レチノールが好ましい。 Vitamin A used in the present invention has an action of increasing dark adaptation of the retina, an abnormal dryness and keratinization of the skin and mucous membranes, and an action of increasing resistance to diseases. Vitamin A is not particularly limited, but specific examples thereof include retinol, dehydroretinol, retinol acetate, retinol palmitate, or derivatives thereof. Retinoids that are analogs of retinol include Derivatives such as retinal, retinal ester, retinoic acid and the like can be mentioned. In the present invention, retinol and its derivative are preferably retinol palmitate.
本発明において使用されるビタミンＢ１はチアミンで、チアミンピロリン酸として作用し、欠乏症に脚気、ウエルニッケ脳症がある。ビタミンＢ群は補酵素となり生体化学反応に寄与し、チアミンピロリン酸は解糖、すなわち細胞が糖質をエネルギーとして利用する際に欠かせない補酵素であり、又中枢神経、末梢神経の働きを正常に保つ働きがある。ビタミンＢ１としては特に限定されるものではないが、その具体例としてチアミンピロリン酸，フルスルチアミン、ベンフォチアミン等の誘導体が挙げられる。本発明において、チアミン、その誘導体としてはチアミン硝化物が好ましい。 Vitamin B1 used in the present invention is thiamine, which acts as thiamine pyrophosphate, and there are deficiencies such as beriberi and Wernicke encephalopathy. Vitamin B group becomes a coenzyme and contributes to the biochemical reaction, and thiamine pyrophosphate is glycolytic, that is, a coenzyme that is indispensable when cells use carbohydrates as energy, and also functions as the central and peripheral nerves. There is work to keep it normal. Although it does not specifically limit as vitamin B1, Derivatives, such as thiamine pyrophosphate, a fursultiamine, a benfotiamine, are mentioned as the specific example. In the present invention, thiamine nitrate is preferred as thiamine and its derivatives.
本発明において使用されるビタミンＢ２はリボフラビンで、体内ではフラビンアデニンジヌクレオチドとして作用し、脂肪代謝の補酵素として作用し、セレンというミネラルとともに過酸化脂質の分解に働く、欠乏症に口角炎、口唇炎、舌炎、脂漏性皮膚炎、眼瞼炎等がある。本発明においてはリボフラビンが好ましい。Vitamin B2 used in the present invention is riboflavin, which acts as a flavin adenine dinucleotide in the body, acts as a coenzyme for fat metabolism, and works to decompose lipid peroxide together with a mineral called selenium. , Glossitis, seborrheic dermatitis, blepharitis, etc. Riboflavin is preferred in the present invention.
本発明において使用されるビタミンＢ６はピリドキシン、ピリドキサール、ピリドキサミンと、これらにリン酸が結合した６種類あり、体内ではリン酸ピリドキサールとして作用し、アミノ酸の合成、分解酵素の補酵素として、又神経細胞の興奮を抑制するγ−アミノ酪酸（ＧＡＢＡ）という神経伝達物質の合成に働き、Ｂ６欠乏症はあまり知られていないが、Ｂ２、ニコチン酸欠乏に合併して皮膚炎を助長している可能性がある。本発明においてはピリドキシンが好ましい。 There are six types of vitamin B6 used in the present invention, pyridoxine, pyridoxal, pyridoxamine, and phosphoric acid bound to these. In the body, it acts as pyridoxal phosphate, synthesizing amino acids, coenzymes for degrading enzymes, and nerve cells It works in the synthesis of neurotransmitter γ-aminobutyric acid (GABA) that suppresses the excitement of B6, and B6 deficiency is not well known, but it may be associated with B2 and nicotinic acid deficiency to promote dermatitis is there. In the present invention, pyridoxine is preferred.
本発明において使用されるビタミンＢ１２はコバラミンで、シアンがついてシアノコバラミン、ヒドロキソコバラミンがあり、肝臓で活性型のアデノシルコバラミンやメチルコバラミンになり作用する。生理作用は核酸の合成作用があり、欠乏症に悪性貧血、消化器疾患、知覚異常の神経障害がある。本発明においてはシアノコバラミンが好ましい Vitamin B12 used in the present invention is cobalamin, cyan, followed by cyanocobalamin and hydroxocobalamin, which act as active forms of adenosylcobalamin and methylcobalamin in the liver. Physiological effects include nucleic acid synthesis, and deficiencies include pernicious anemia, gastrointestinal disorders, and sensory abnormal neuropathy. In the present invention, cyanocobalamin is preferable.
本発明において使用されるアスコルビン酸もしくはその塩は、当初は抗壊血病作用を有すると考えられてきたが、更に生体内における細胞間基質とコラーゲンの形成維持に必要で、アスコルビン酸の投与により、コラーゲンの増加が見られる。又メラニン色素生成に関与し、チロジンからメラニンへの生成過程を抑制する。更に酸化型の濃色メラニンを還元型の淡色メラニンに変える作用があり、色素の異常沈着を防ぐ。更に蛋白質の代謝、内分泌機能にも関与する重用な物質である。ビタミンＣ類としては特に限定されるものではないが、その具体例として、Ｌ−アスコルビン酸およびその誘導体またはそれらの塩としては、塩酸塩、硝酸塩、硫酸塩等の鉱酸塩、ナトリウム塩、カリウム塩、カルシウム塩、マグネシウム塩等のアルカリ金属塩、アルカリ土類金属塩等を挙げることが出来る。Ｌ−アスコルビン酸、およびその誘導体またはそれらの塩としては、Ｌ−アスコルビン酸、Ｌ−アスコルビン酸ナトリウム、Ｌ−アスコルビン酸カリウム、Ｌ−アスコルビン酸カルシウム、Ｌ−アスコルビン酸マグネシウムなどのＬ−アスコルビン酸塩、Ｌ−アスコルビン酸モノステアレート、Ｌ−アスコルビン酸モノパルミテート、Ｌ−アスコルビン酸モノオレエート等のアスコルビン酸モノアルキルまたはモノアルケニルエステル類；Ｌ−アスコルビン酸ジステアレート、Ｌ−アスコルビン酸ジパルミテート、Ｌ−アスコルビン酸ジオレエート等のＬ−アスコルビン酸ジアルキルまたはジアルケニルエステル類；Ｌ−アスコルビン酸トリステアレート、Ｌ−アスコルビン酸トリパルミテート、Ｌ−アスコルビン酸トリオレエート等のＬ−アスコルビン酸トリアルキルまたはトリアルケニルエステル類；Ｌ−アスコルビル硫酸、Ｌ−アスコルビル硫酸ナトリウム、Ｌ−アスコルビル硫酸カリウム、Ｌ−アスコルビル硫酸マグネシウム、Ｌ−アスコルビル硫酸カルシウム等のＬ−アスコルビン酸硫酸エステル類；Ｌ−アスコルビルリン酸、Ｌ−アスコルビルリン酸ナトリウム、Ｌ−アスコルビルリン酸カリウム、Ｌ−アスコルビルリン酸マグネシウム、Ｌ−アスコルビルリン酸カルシウム等のＬ−アスコルビン酸リン酸エステル類など；Ｌ−アスコルビン酸グリコシド等のアスコルビン酸配糖体などを挙げることが出来る。本発明において、Ｌ−アスコルビン酸、その誘導体またはそれらの塩としてはＬ−アスコルビン酸が好ましい。 Ascorbic acid or a salt thereof used in the present invention was originally considered to have an anti-scurvy effect, but is further necessary for maintaining the formation of intercellular matrix and collagen in vivo, and ascorbic acid is administered by administration. Increase in collagen is seen. It is also involved in melanin pigment production and suppresses the production process from tyrosin to melanin. In addition, it has the effect of changing oxidized dark melanin to reduced light melanin, preventing abnormal pigmentation. Furthermore, it is an important substance involved in protein metabolism and endocrine function. Although it does not specifically limit as vitamin Cs, As the specific example, L-ascorbic acid and its derivative (s) or those salts are mineral salts, such as hydrochloride, nitrate, a sulfate, sodium salt, potassium Examples thereof include alkali metal salts such as salts, calcium salts and magnesium salts, and alkaline earth metal salts. Examples of L-ascorbic acid and its derivatives or salts thereof include L-ascorbic acid salts such as L-ascorbic acid, sodium L-ascorbate, potassium L-ascorbate, calcium L-ascorbate, and magnesium L-ascorbate. L-ascorbic acid monostearate, L-ascorbic acid monopalmitate, ascorbic acid monoalkyl or monoalkenyl esters such as L-ascorbic acid monooleate; L-ascorbic acid distearate, L-ascorbic acid dipalmitate, L-ascorbic acid L-ascorbic acid dialkyl or dialkenyl esters such as dioleate; L-ascorbic acid tristearate, L-ascorbic acid tripalmitate, L-ascorbic acid trioleate, etc. L-ascorbic acid sulfates such as L-ascorbyl sulfate, sodium L-ascorbyl sulfate, potassium L-ascorbyl sulfate, magnesium L-ascorbyl sulfate, calcium L-ascorbyl sulfate; L-ascorbyl sulfate; L-ascorbic acid phosphates such as ascorbyl phosphate, sodium L-ascorbyl phosphate, potassium L-ascorbyl phosphate, magnesium L-ascorbyl phosphate and calcium L-ascorbyl phosphate; ascorbic acid such as L-ascorbic acid glycoside Examples include glycosides. In the present invention, L-ascorbic acid, its derivative or a salt thereof is preferably L-ascorbic acid.
本発明において使用されるビタミンＤはＤ２（エルゴカルシフエロール）、Ｄ３（コレカルシフエロール）で、肝臓、腎臓で活性型Ｄとなり、カルシウム代謝調節ホルモンの作用がある。骨粗しよう症に効果があり、欠乏症は乳幼児のくる病、成人でも骨軟化症になる。本発明においてはＤ２、エルゴカルシフエロールが好ましい。 Vitamin D used in the present invention is D2 (ergocalciferol) or D3 (cholecalciferol), and becomes active D in the liver or kidney, and has the action of a calcium metabolism regulating hormone. It is effective for osteoporosis. Deficiency causes rickets in infants and osteomalacia even in adults. In the present invention, D2 and ergocalciferol are preferred.
本発明において使用されるビタミンＥは妊娠、出産と関係あり、不老長寿の薬と言われ、末梢血管を拡張し血液循環をよくする働きがあり、ビタミンＥとコエンザイムＱ１０は両成分が協力して電子の移動を調整し、体内の酸化反応を抑制するなど、非常に関係の強い成分同士として知られている。ビタミンＥ類としては、特に限定されるものではないが、その具体例としてはコハク酸トコフエロール、酢酸トコフエロール、ニコチン酸トコフエロールもしくはこれらの誘導体が挙げられる。本発明において、ビタミンＥ、その誘導体としては酢酸トコフエロールが好ましい。 Vitamin E used in the present invention is related to pregnancy and childbirth, and is said to be a drug for longevity, and has the function of expanding peripheral blood vessels and improving blood circulation. Vitamin E and coenzyme Q10 cooperate with each other. It is known as a component with very strong relations, such as adjusting the movement of electrons and suppressing the oxidation reaction in the body. Vitamin E is not particularly limited, and specific examples thereof include tocopherol succinate, tocopherol acetate, tocopherol nicotinate or derivatives thereof. In the present invention, vitamin E and its derivative are preferably tocopherol acetate.
本発明において使用されるパントテン酸カルシウムは細胞内糖質代謝のコエンザイムＡの構成成分で生命活動に必須で、紫外線による皮膚炎に、毛髪の健康に効果がある。本発明においてはパントテン酸カルシウムが好ましい。 Calcium pantothenate used in the present invention is a component of coenzyme A for intracellular carbohydrate metabolism and essential for life activity, and is effective for dermatitis due to ultraviolet rays and hair health. In the present invention, calcium pantothenate is preferable.
本発明において使用されるニコチン酸アミドは脱水素酵素の補酵素で糖質、脂肪からエネルギー産生に不可欠のビタミンで、高脂血漿に効果があり、欠乏症にペラグラがあり、欠乏が進むと認知障害をきたす。本発明においてはニコチン酸アミドが好ましい。 Nicotinamide used in the present invention is a dehydrogenase coenzyme, an essential vitamin for energy production from carbohydrates and fats, effective in high-fat plasma, pellagra in deficiency, and cognitive impairment as deficiency progresses Bring In the present invention, nicotinamide is preferred.
本発明において使用される葉酸は核酸の成分となるプリン核、ピリミジン核合成酵素の補酵素で、欠乏症に悪性貧血がある。本発明においては葉酸が好ましい。Folic acid used in the present invention is a coenzyme of purine nuclei and pyrimidine nucleosynthesis enzymes that are components of nucleic acids, and there is pernicious anemia in deficiency. Folic acid is preferred in the present invention.
ワクシニアウイルス接種家兎炎症皮膚抽出液は皮膚の掻痒、冷感、異常知覚に、腰痛症、神経痛等の痛みに効果があり、抗アレルギー作用もある医薬品である。 Vaccinia virus-inoculated rabbit inflammation skin extract is an effective drug for itching, cooling and abnormal perception of skin, as well as low back pain, neuralgia, and other anti-allergic effects.
以下に実施例を示して本発明を説明するが、本発明は以下の実施例に限定されるものではない。 The present invention will be described below with reference to examples, but the present invention is not limited to the following examples.
動脈硬化改善剤の製法
動脈硬化改善剤は以下の組成で、常法により製造した。ビタミンＡ，Ｂ６，Ｄ，Ｅ，ニコチン酸には過剰症があり、過剰にならぬよう注意が必要。
アデリール錠１０ｍｇ（コエンザイムＱ１０） ６００錠
ハイチオール散３２％（Ｌシステイン） ５２ｇ
レチノールパルミチン酸エステル レチノールとして５０００００ＩＵ
チアミン硝化物 ２００ｍｇ
リボフラビン ３００ｍｇ
ピリドキシン塩酸塩 ２００ｍｇ
シアノコバラミン ２００μｇ
アスコルビン酸（日本薬局方） ４０ｇ
エルゴカルシフエロール ４００００ＩＵ
トコフエロール酢酸エステル ２０ｇ
パントテン酸カルシウム １ｇ
ニコチン酸アミド ２ｇ
葉酸 １００ｍｇ
ワクシニアウイルス接種家兎炎症皮膚抽出液含有製剤４単位 ２０錠
精製水 １８００ｍｌMethod for producing arteriosclerosis improving agent The arteriosclerosis improving agent was prepared by a conventional method with the following composition. Vitamins A, B 6 , D, E, and nicotinic acid have a hyperplasia, so be careful not to overdo it.
Adeliel Tablets 10mg (Coenzyme Q10) 600 Tablets Hythiol Powder 32% (L Cysteine) 52g
Retinol palmitate ester 50000 IU as retinol
Thiamine nitrate 200mg
Riboflavin 300mg
Pyridoxine hydrochloride 200mg
Cyanocobalamin 200μg
Ascorbic acid (Japanese Pharmacopoeia) 40g
Ergocalciferol 40000 IU
Tocopherol acetate 20g
Calcium pantothenate 1g
Nicotinamide 2g
Folic acid 100mg
Vaccinia virus inoculated rabbit inflammation skin extract-containing preparation 4 units 20 tablets Purified water 1800 ml
６０前：６０才代前半の血管の硬さに相当します。
４０後：４０才代後半の血管の硬さに相当します。 の略です。Before 60: Corresponds to the hardness of blood vessels in the early 60s.
After 40: Corresponds to the hardness of blood vessels in the late 40s. Stands for.
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