JPH0475205B2 - - Google Patents
Info
- Publication number
- JPH0475205B2 JPH0475205B2 JP3866684A JP3866684A JPH0475205B2 JP H0475205 B2 JPH0475205 B2 JP H0475205B2 JP 3866684 A JP3866684 A JP 3866684A JP 3866684 A JP3866684 A JP 3866684A JP H0475205 B2 JPH0475205 B2 JP H0475205B2
- Authority
- JP
- Japan
- Prior art keywords
- lipoic acid
- effect
- administration
- acid
- immune
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 229960002663 thioctic acid Drugs 0.000 claims description 27
- 235000019136 lipoic acid Nutrition 0.000 claims description 26
- 239000002955 immunomodulating agent Substances 0.000 claims description 9
- 229940121354 immunomodulator Drugs 0.000 claims description 9
- 230000002584 immunomodulator Effects 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 claims 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 25
- 230000000694 effects Effects 0.000 description 12
- 229920006926 PFC Polymers 0.000 description 7
- 230000036737 immune function Effects 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000002519 immonomodulatory effect Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229960004397 cyclophosphamide Drugs 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000004988 splenocyte Anatomy 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229960001614 levamisole Drugs 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical group CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 201000010000 Agranulocytosis Diseases 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 206010018687 Granulocytopenia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940084983 cyclophosphamide 50 mg Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000000724 thymus hormone Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明はリポ酸（チオクト酸）を有効成分と
する免疫調節剤に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an immunomodulator containing lipoic acid (thioctic acid) as an active ingredient.
一般に免疫調節作用とは免疫機能が正常な状態
ではほとんど影響を与えずに、低下した免疫機能
を増強させ、逆に免疫機能亢進状態ではそれを低
下させ、それぞれ免疫機能の異常を是正し、正常
な状態に戻すような作用と理解される。免疫機能
の亢進も抑制機構の低下が原因のこともあり、ま
た免疫機能の低下状態も抑制機構の亢進が原因に
なりうるので、免疫調節機構の制御に乱れに対し
て調節的に作用し、それを是正する方向に働くの
が免疫調節作用といえる。 In general, immunomodulatory effects have little effect when the immune system is normal, reinforcing the weakened immune function, and conversely decreasing it when the immune system is hyperactive, correcting abnormalities in the immune function and normalizing it. It can be understood as an action that restores a normal state. Enhancement of immune function can also be caused by a decrease in the suppressive mechanism, and a state of decreased immune function can also be caused by an increase in the suppressive mechanism. It can be said that immunomodulatory action works to correct this.
これまでの免疫調節剤（レバミゾール、胸腺ホ
ルモン等）はそれを用いた治療において、多くの
副作用が報告されている。たとえばレバミゾール
については吐気、発疹、血液障害等が方向されて
おり、中でも最も重大な副作用は顆粒球減少症で
あり、治療中止により消失する現象であるが、長
期にわたつて用いる時は白血球数の厳密な追跡を
行なわねばならない。 Many side effects have been reported in treatments using conventional immunomodulators (levamisole, thymus hormone, etc.). For example, levamisole has been associated with nausea, rash, blood disorders, etc., and the most serious side effect is granulocytopenia, a phenomenon that disappears when treatment is discontinued, but when used for a long period of time, it can cause a decrease in the white blood cell count. Strict tracking must be carried out.
上述した如く、公知の免疫調節剤に通常認めら
れる重篤な副作用を持たない新しい免疫調節剤が
強く望まれている。近年種々の理由により抑制さ
れた免疫機能を回復させ、亢進した免疫機能を正
常に復し、また正常な免疫機能を強化、維持する
ことにより、ウイルス、細菌など病原寄生体の生
体内感染や増殖に対し、またガンの如き生体内に
生じた異物の増殖に対して抵抗性を強める免疫調
節剤の重要性が著しく増加しつつある。またこの
ような薬剤は各種アレルギー、リウマチ性関節炎
などの疾患にも適用が望まれている。 As mentioned above, there is a strong need for new immunomodulators that do not have the serious side effects usually associated with known immunomodulators. By restoring immune function that has been suppressed due to various reasons in recent years, restoring enhanced immune function to normal, and strengthening and maintaining normal immune function, we can prevent in-vivo infection and proliferation of pathogenic parasites such as viruses and bacteria. In contrast, the importance of immunomodulators that enhance resistance to the growth of foreign substances such as cancer in living bodies is increasing significantly. It is also desired that such drugs be applied to diseases such as various allergies and rheumatoid arthritis.
本発明者らはこのような目的に使用するための
免疫調節剤を種々検索した結果リポ酸が優れた免
疫調節作用を有することを見出した。リポ酸（チ
オクト酸）はこれまで肝疾患治療に広く使用され
てきた安全性の高い薬剤である。その薬理作用と
しては肝機能亢進作用、解毒作用等が報告されて
いる。しかしながら含イオウ脂肪酸であるリポ酸
が免疫調節作用を有することはこれまで知られて
いず、肝疾患治療剤とは異なる免疫調節剤として
使用された例は未だない。本発明者らは鋭意検討
した結果、おどろくべきことにジスルフイド結合
を有する生体成分であるリポ酸（チオクト酸DL
体、天然物はＤ体リポ酸）において優れた免疫調
節作用を有することを見いだし、本発明を完成す
るに至つたものである。 The present inventors searched for various immunomodulators for use in this purpose and found that lipoic acid has an excellent immunomodulatory effect. Lipoic acid (thioctic acid) is a highly safe drug that has been widely used to treat liver diseases. Its pharmacological effects include hepatic function enhancing effect and detoxifying effect. However, it has not been known so far that lipoic acid, which is a sulfur-containing fatty acid, has an immunomodulatory effect, and there has been no example of its use as an immunomodulatory agent other than a therapeutic agent for liver diseases. As a result of intensive studies, the present inventors surprisingly discovered that lipoic acid (thioctic acid DL), a biological component with disulfide bonds,
The inventors discovered that D-lipoic acid, a natural product, has an excellent immunomodulatory effect, leading to the completion of the present invention.
以下に本発明のリポ酸の免疫調節剤に関するイ
ンビトロ、およびインビボの薬理効果について具
体的に説明する。 The in vitro and in vivo pharmacological effects of the lipoic acid immunomodulator of the present invention will be specifically explained below.
実施例 １
〔薬理試験〕
(1) マウス脾細胞を用いたPFC応答に及ぼす作
用
BALB／ｃマウス脾細胞を用いてリポ酸の抗
SRBC PFC応答に及ぼす作用を検討した。Example 1 [Pharmacological test] (1) Effect of lipoic acid on PFC response using mouse splenocytes.
The effect on SRBC PFC response was investigated.
BALB／ｃマウス脾細胞６×106個をSRBCお
よびリポ酸と共に10％牛胎児血清を含むRPMI−
1640培地にてCO2インキユベーター（37℃）中で
４日間Mishell−Dutton法により培養し、出現す
るdirect PFC数をJerneの方法（Science，140
巻、405頁、1963年）で測定した。結果を第１図
に示した。 6 × 10 6 BALB/c mouse splenocytes were incubated with SRBC and lipoic acid in RPMI containing 10% fetal bovine serum.
Cultured in 1640 medium in a CO 2 incubator (37℃) for 4 days using the Mishell-Dutton method, and the number of direct PFCs that appeared was calculated using Jerne's method (Science, 140
Vol. 405, 1963). The results are shown in Figure 1.
第１図から明らかなように、リポ酸の抗SRBC
PFC応答に及ぼす作用は10-5Ｍ付近で強い抗体応
答促進効果を示した。ここ及びあとでいうSRBC
とは羊赤血球で、PFCとは抗羊赤血球プラーク
形成細胞応答を示してしる。 As is clear from Figure 1, the anti-SRBC effect of lipoic acid
The effect on PFC response showed a strong antibody response promoting effect at around 10 -5 M. SRBC referred to here and later
refers to sheep red blood cells, and PFC refers to anti-sheep red blood cell plaque-forming cell responses.
(2) Cyclophosphamide処置により低下した免疫
応答のリポ酸投与による回復
Cyclophosphamideを投与し低下させた免疫応
答能の回復効果を検討した。実験はBALB／ｃ
系の雌性マウスを１群につき４匹用い、マウスの
尾静脈内にSRBCを１×108個注射しマウスを免
疫した。cyclophosphamideを免疫２日前から１
日１回50mgを２日間腹腔内投与し、免疫の日から
リポ酸を１日２回25mg／Kg経口投与した。免疫後
４日目に脾臓を摘出して、出現するPFC数を
Jerneの方法で測定しリポ酸の免疫応答の回復効
果を求め、その結果を第２図に示した。(2) Recovery of immune response decreased by cyclophosphamide treatment by lipoic acid administration The effect of recovery of immune response decreased by administration of cyclophosphamide was investigated. The experiment is BALB/c
Four female mice of the same strain were used per group, and 1×10 8 SRBC were injected into the tail vein of the mice to immunize them. 2 days before immunization with cyclophosphamide
50 mg of lipoic acid was administered intraperitoneally once a day for 2 days, and from the day of immunization, 25 mg/Kg of lipoic acid was orally administered twice a day. On the fourth day after immunization, the spleen was removed and the number of PFCs that appeared was calculated.
The recovery effect of lipoic acid on the immune response was measured by Jerne's method, and the results are shown in FIG.
第２図から明らかなようにリポ酸は免疫応答を
回復させた。 As is clear from Figure 2, lipoic acid restored the immune response.
(3) ddY系雄性マウス（５〜６週令）（体重25〜
30ｇ）を１群８匹で用い、0.5％メチルセルロ
ーズ液に懸濁させたリポ酸を腹腔内投与後、７
日間経過を観察しLD50値を求めた。腹腔内投
与の場合のLD50値は160〜275mg／Kgであつた。(3) ddY male mouse (5-6 weeks old) (body weight 25~
After intraperitoneal administration of lipoic acid suspended in 0.5% methylcellulose solution, 30g) was used in 8 animals per group.
The daily progress was observed and the LD 50 value was determined. The LD 50 values for intraperitoneal administration were 160-275 mg/Kg.
以上説明したように、本発明のリポ酸は免疫調
節剤として有用であり、通常の処方により経口的
または非経口的に投与することができる。経口的
には錠剤、カプセル剤、または散剤などの医薬用
製剤とし、非経口投与では皮下、静脈または筋肉
内注射などの注射剤として用いられる。これらの
製剤において常法に従つて主薬に賦形剤、溶解補
助剤、安定化剤などの添加も可能であり、また必
要に応じて結合剤等などを加えてもよい。その投
与量は投与方法、症状などによつて異なるが、通
常、成人に対する一回投与量はリポ酸として１〜
300mgであり、１日１回または症状に応じてそれ
以上投与することもできる。また本剤と他剤例え
ば抗菌剤、抗炎症剤、抗腫瘍剤などとの併用も可
能である。 As explained above, the lipoic acid of the present invention is useful as an immunomodulator, and can be administered orally or parenterally using a conventional prescription. For oral administration, it is used as a pharmaceutical preparation such as a tablet, capsule, or powder, and for parenteral administration, it is used as an injection such as subcutaneous, intravenous, or intramuscular injection. In these preparations, excipients, solubilizing agents, stabilizers, etc. may be added to the main drug according to conventional methods, and binders, etc. may also be added as necessary. The dosage varies depending on the administration method, symptoms, etc., but a single dose for adults is usually 1 to 10% as lipoic acid.
The dose is 300 mg, and it can be administered once a day or more depending on the symptoms. It is also possible to use this drug in combination with other drugs such as antibacterial agents, anti-inflammatory agents, and antitumor agents.
次に製剤例をあげて説明を加える。 Next, an explanation will be given by giving examples of formulations.
製剤例１ 経口用カプセル剤
リポ酸 10mg
乳糖 40mg
結晶セルロース 50mg
上記の処方の粉末を混合し、ゼラチンカプセル
に入れ、カプセル剤とした。Formulation Example 1 Oral Capsules Lipoic acid 10mg Lactose 40mg Crystalline cellulose 50mg The powders of the above formulation were mixed and placed in gelatin capsules to form capsules.
製剤例２ 注射剤(1)
リポ酸 10mg
ベンジルアルコール ２ml
上記溶液を褐色バイアルに封入し、使用時に皮
下、あるいは筋肉注射剤として用いる。Formulation Example 2 Injection (1) Lipoic acid 10 mg Benzyl alcohol 2 ml The above solution is sealed in a brown vial and used as a subcutaneous or intramuscular injection.
製剤例３ 注射剤(2)
リポ酸 25mg
ベンジルアルコール ５ml
上記溶液を褐色バイアルに封入し、使用時に静
脈注射剤として用いる。Formulation Example 3 Injection (2) Lipoic acid 25 mg Benzyl alcohol 5 ml The above solution is sealed in a brown vial and used as an intravenous injection at the time of use.
第１図は実施例１においてマウス脾細胞を用い
たPFC応答に及ぼす作用を示す図で、第２図は
実施例１において免疫応答のリポ酸投与による回
復をみた図である。
CY……Cyclophosphamide、Lip……リポ酸。
FIG. 1 is a diagram showing the effect on the PFC response using mouse splenocytes in Example 1, and FIG. 2 is a diagram showing the recovery of the immune response by lipoic acid administration in Example 1. CY...Cyclophosphamide, Lip...Lipoic acid.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3866684A JPS60184011A (en) | 1984-03-02 | 1984-03-02 | Immuno-regulator |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3866684A JPS60184011A (en) | 1984-03-02 | 1984-03-02 | Immuno-regulator |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60184011A JPS60184011A (en) | 1985-09-19 |
| JPH0475205B2 true JPH0475205B2 (en) | 1992-11-30 |
Family
ID=12531590
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3866684A Granted JPS60184011A (en) | 1984-03-02 | 1984-03-02 | Immuno-regulator |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60184011A (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3615710A1 (en) * | 1986-05-09 | 1987-11-26 | Hoechst Ag | PREPARATIONS FOR THE SYNTHESIS OF PROSTAGLANDINES AND HYDROXY FATTY ACIDS IN BIOLOGICAL SYSTEMS |
| DE59010810D1 (en) * | 1989-11-09 | 1998-04-16 | Asta Medica Ag | Medicament containing R-alpha-lipoic acid or S-alpha-lipoic acid as active ingredient |
| SE508601C2 (en) * | 1989-11-09 | 1998-10-19 | Asta Medica Ag | Medicines containing as active substance carboxylic acids containing sulfur and their use for the control of retroviruses |
| US5569670A (en) * | 1992-06-05 | 1996-10-29 | Asta Medica Aktiengesellschaft | Combination medications containing alpha-lipoic acid and related |
| US6191162B1 (en) | 1998-05-28 | 2001-02-20 | Medical Research Institute | Method of reducing serum glucose levels |
| US6905707B2 (en) | 1998-05-28 | 2005-06-14 | Medical Research Institute | Controlled release arginine alpha ketoglutarate |
| US6197340B1 (en) | 1998-05-28 | 2001-03-06 | Medical Research Institute | Controlled release lipoic acid |
| US8592479B2 (en) * | 2000-10-31 | 2013-11-26 | Hill's Pet Nutrition, Inc. | Antioxidant-containing food composition for use in enhancing antiviral immunity in companion animals |
| JP5228398B2 (en) * | 2007-08-16 | 2013-07-03 | 日立電線株式会社 | Composite cable |
| EP2364098B1 (en) * | 2008-12-16 | 2016-10-12 | Hill's Pet Nutrition, Inc. | Antioxidant-containing food composition for use in enhancing antiviral immunity in companion animals |
-
1984
- 1984-03-02 JP JP3866684A patent/JPS60184011A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60184011A (en) | 1985-09-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100638684B1 (en) | Use of 9-deoxy-2',9-alpha-methano-3-oxa-4,5,6-trinor-3,7-1',3'-interphenylene-13,14-dihydro-prostaglandin f1 to treat peripheral vascular disease | |
| EP1484059B1 (en) | Antiviral compositions comprising phenylacetic acid derivatives | |
| CA2312475A1 (en) | Method of suppressing .beta.-amyloid-related changes in alzheimer's disease | |
| TW200425907A (en) | Composition containing dipeptide of histidine and alanine for reducing uric acid | |
| KR101390144B1 (en) | Therapeutic agent for inflammatory bowel disease | |
| JPH0475205B2 (en) | ||
| TW200815014A (en) | Method of improved diuresis in individuals with impaired renal function | |
| JPH0637395B2 (en) | A drug for treating amyotrophic lateral sclerosis, containing a dipeptide derivative | |
| WO2002060431A1 (en) | Remedies/preventives for inflammatory diseases | |
| EP0629400A1 (en) | Idebenone compositions for treating Alzheimer's disease | |
| JPH08512311A (en) | Arsenic medicine for treating chronic fatigue syndrome | |
| JPS61176524A (en) | Antiinflammatory composition | |
| JP3982889B2 (en) | Pharmaceutical preparations containing ibuprofen | |
| JP3253878B2 (en) | Formulations for iron chelation, methods of preparing the same and methods of treating Mediterranean anemia | |
| JPH06172187A (en) | Medicine for muscular dystrophy | |
| Alergant | Treatment of gonorrhoea with amoxycillin. | |
| JP5376785B2 (en) | Pharmaceutical composition | |
| US20190381034A1 (en) | Pharmaceutical composition and method for acute on chronic liver failure and related liver diseases | |
| JP5366386B2 (en) | Nerve cell activation and nerve elongation promoting composition | |
| JPS63179832A (en) | Therapy for inflammatory arthritic disease | |
| JP2009084211A (en) | Composition for nerve cell activation | |
| JPS60184012A (en) | Immuno-regulator | |
| JPS58167514A (en) | Immunological regulating agent | |
| KR20230157119A (en) | Pharmaceutical composition for preventing or treating hepatitis B | |
| JPH0912451A (en) | Anti-helicobacter pyrolii agent |