JPH02145517A - Preventive and remedy for crisis of aids and treating composition thereof - Google Patents
Preventive and remedy for crisis of aids and treating composition thereofInfo
- Publication number
- JPH02145517A JPH02145517A JP63299202A JP29920288A JPH02145517A JP H02145517 A JPH02145517 A JP H02145517A JP 63299202 A JP63299202 A JP 63299202A JP 29920288 A JP29920288 A JP 29920288A JP H02145517 A JPH02145517 A JP H02145517A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- aids
- interferon
- present
- compound
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 35
- 230000003449 preventive effect Effects 0.000 title 1
- 230000000694 effects Effects 0.000 claims abstract description 21
- 102000014150 Interferons Human genes 0.000 claims abstract description 17
- 108010050904 Interferons Proteins 0.000 claims abstract description 17
- 229940079322 interferon Drugs 0.000 claims abstract description 17
- 208000030507 AIDS Diseases 0.000 claims abstract description 15
- 239000000126 substance Substances 0.000 claims abstract description 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- -1 organogermanium compound Chemical class 0.000 claims abstract description 5
- 238000002844 melting Methods 0.000 claims abstract description 3
- 230000008018 melting Effects 0.000 claims abstract description 3
- 230000003405 preventing effect Effects 0.000 claims abstract description 3
- 239000013078 crystal Substances 0.000 claims abstract 2
- 238000000354 decomposition reaction Methods 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims description 10
- 150000002291 germanium compounds Chemical class 0.000 claims description 8
- 229920000642 polymer Polymers 0.000 claims description 6
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 235000000346 sugar Nutrition 0.000 claims description 2
- 150000008163 sugars Chemical class 0.000 claims description 2
- 239000002075 main ingredient Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 11
- 230000002708 enhancing effect Effects 0.000 abstract description 7
- 241000712461 unidentified influenza virus Species 0.000 abstract description 7
- 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 abstract description 3
- 239000008101 lactose Substances 0.000 abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 3
- 102000040430 polynucleotide Human genes 0.000 abstract description 2
- 108091033319 polynucleotide Proteins 0.000 abstract description 2
- 239000002157 polynucleotide Substances 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 16
- 241000725303 Human immunodeficiency virus Species 0.000 description 10
- 230000016396 cytokine production Effects 0.000 description 8
- 241000700605 Viruses Species 0.000 description 7
- 102000003996 Interferon-beta Human genes 0.000 description 5
- 108090000467 Interferon-beta Proteins 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 229910052732 germanium Inorganic materials 0.000 description 4
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 4
- 102000006992 Interferon-alpha Human genes 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 206010070834 Sensitisation Diseases 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 229940044627 gamma-interferon Drugs 0.000 description 3
- 206010022000 influenza Diseases 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000008313 sensitization Effects 0.000 description 3
- 241000711975 Vesicular stomatitis virus Species 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000013022 formulation composition Substances 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 241000221198 Basidiomycota Species 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000003865 nucleic acid synthesis inhibitor Substances 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003253 viricidal effect Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000012138 yeast extract Substances 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明はエイズ治療剤及び該治療用組成物に係るもので
ある。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to an AIDS therapeutic agent and a therapeutic composition thereof.
（従来技術）
後天性免疫不全症候群（エイズ）はＨｕｍａｎ Ｉｍｍ
ｕｎｏｄｅｆｉｃｉｅｎｃｙ Ｖｉｒｕｓ （以下ＨＩ
Ｖと略す）疾患であるがヒトがこのウィルスに感染する
と、リンパ球のヘルパーＴＨｉ胞が破壊されるため細胞
免疫不全となり、日和見感染症、カポシ肉種等となり死
亡するものである。(Prior art) Acquired immunodeficiency syndrome (AIDS)
Undeficiency Virus (HI
When humans are infected with this virus, the helper THi cells in the lymphocytes are destroyed, resulting in cellular immunodeficiency, resulting in opportunistic infections, Kaposi's syndrome, etc., and death.
他の肝炎ウィルス、白血病ウィルス等と比較して極めて
発症率と発症後の致命率が高く、しかも現在使用されて
いる薬剤は核酸合成阻害系薬剤が主流であるため、殺ウ
イルス作用以上に正常組織の破壊が著しい欠陥があり、
安全性が高く、治癒率の高い薬剤の開発が望まれている
現況にある。Compared to other hepatitis viruses, leukemia viruses, etc., the incidence rate and fatality rate after onset are extremely high.Moreover, the drugs currently in use are mainly nucleic acid synthesis inhibitors, so they have a stronger effect on normal tissues than their virucidal effect. There is a defect that causes significant damage to the
There is currently a desire to develop drugs that are highly safe and have a high cure rate.
本発明に使用されるゲルマニウム重合体については、特
許公開５４−１１５３２４号（免疫賦活作用）特許公開
５６−１６７２２２号（抗ウイルス作用）等に上位概念
として化合物存在の可能性と単なる賦形剤としての組成
形態の記載はあるが本重合体の物性、組成の有効性が特
定されてはおらず、エイズの治療剤としての記載ちない
。Regarding the germanium polymer used in the present invention, the possibility of the presence of a compound as a general concept and the possibility that it can be used as a mere excipient are described in Japanese Patent Publication No. 54-115324 (immunostimulatory effect) and Japanese Patent Publication No. 56-167222 (antiviral effect). Although there is a description of the composition form of this polymer, the physical properties of this polymer and the effectiveness of the composition are not specified, and there is no description of its use as a therapeutic agent for AIDS.
又、新聞等にあっても、エイズ治療薬として、本出願人
名とゲルマニウム化合物として有効可能性が報道されて
いるが、本物質と組成が特定され公知化されているもの
ではない。In addition, newspapers and the like have reported that the applicant's name and germanium compound may be effective as a therapeutic agent for AIDS, but the substance and its composition have not been identified and made public.
なお、本出願人等は本物質を肝炎の治療剤として上市し
つつあり、エイズ治療の治癒率向上の社会的必要性から
実際エイズ患者に投与し有効な結果を得たため本発明を
完成したものである。The present applicant and others are in the process of putting this substance on the market as a therapeutic agent for hepatitis, and due to the social need to improve the cure rate of AIDS treatment, they completed the present invention after actually administering it to AIDS patients and obtaining effective results. It is.
（発明が解決しようとする課題）
従来公知の有機ゲルマニウム化合物類（特公昭４６−２
９６４号）は本発明物質と’ｌｆＪ造物性が異なる事、
又、ロットごとに作用が異なり作用程度も明確でないと
言う、致命的な欠陥を有してい匙。(Problem to be solved by the invention) Conventionally known organic germanium compounds (Japanese Patent Publication No. 46-2
No. 964) is different from the substance of the present invention in 'lfJ properties,
In addition, the spoon has a fatal flaw in that the effect differs from lot to lot and the degree of effect is not clear.
なお一部の化合物にあってはインターフェロン産生作用
が報告されているが、作用も不明確であると言う致命的
欠陥のため上市されるには至っていない。これら既知の
有機ゲルマニウム化合物の欠陥を解決すべく研究開発さ
れた化合物が、特許公開５４−１１５３２４号に記載さ
れるゲルマニウム重合性化合物であり、比較的少量で強
力な作用が得られ、医薬品としての諸条件を具備した有
用な化合物であるが、水分等のため長期保存で化学変化
を受けやすく、又、生体に投与した場合にも、安定的な
吸収の必要性が望まれていた。効果の確実性からも、希
少化合物を使用する関係で資源保存の面からも、化合物
本来の持つ少量で強力な作用を直接引出すべく各種処方
組成物研究の必要が望まれていた。Although some compounds have been reported to have interferon-producing effects, they have not been put on the market due to the fatal defect that their effects are unclear. The compound that was researched and developed to solve the defects of these known organic germanium compounds is the germanium polymerizable compound described in Patent Publication No. 54-115324. Although it is a useful compound that meets various conditions, it is susceptible to chemical changes during long-term storage due to water content, and it is desired that it should be absorbed stably when administered to living organisms. From the viewpoint of certainty of efficacy and resource conservation due to the use of rare compounds, it has been desired to conduct research on various formulation compositions in order to directly bring out the powerful effects of compounds in small amounts.
（課題を解決するための手段）
本発明者等はこの様な観点から本化合物について、蛋白
等の高分子化合物や糖類による薬理活性の増強作用を発
見した。（特開昭６０−１９０７１４号等）さらにこれ
らの応用研究の結果、本発明の目的達成のため最適製剤
組成を発見したものである。(Means for Solving the Problems) From this perspective, the present inventors discovered that the pharmacological activity of the present compound is enhanced by polymeric compounds such as proteins and saccharides. (Japanese Unexamined Patent Publication No. 60-190714, etc.) Furthermore, as a result of these applied studies, an optimal formulation composition has been discovered to achieve the object of the present invention.
本発明は経口的に投与する事ができるので、他の薬剤と
比較して使用しやすい利点がある。通常の処方にあたっ
ては、糖類例えば乳糖を５０〜８０％の割合で配合し、
所望により、インターフェロン産生物質、一般の賦形剤
等も薬効に影響を与えない範囲内で処方する事ができる
。Since the present invention can be administered orally, it has the advantage of being easier to use than other drugs. In normal formulations, sugars such as lactose are blended at a ratio of 50 to 80%,
If desired, interferon-producing substances, general excipients, etc. can also be prescribed within the range that does not affect the drug efficacy.
又製剤用高分子性担体としてはゼラチン、ペプシン、血
清アルブミン、グルプリン、プロタミンセルロース系、
ビニール系、アクリル系高分子性担体、ペプトン、ポリ
ペプトン、酵母エキス、トリプトン、トリプトース、デ
キストロース等がある。In addition, as polymeric carriers for formulations, gelatin, pepsin, serum albumin, glupurin, protamine cellulose,
Examples include vinyl-based, acrylic-based polymeric carriers, peptone, polypeptone, yeast extract, tryptone, tryptose, and dextrose.
（発明の効果）
以上要するに、この発明によれば、下記式にて示される
、
＜ ：ａｅｃＨ２ＣＨ２ＣＯＯＨ）ｎ０１．５ｎ（式中
ｎは１又はそれ以上の整数を意味する）にて示され、白
色針状結晶有し、水に対する溶解度が２５度Ｃにおいて
、１．５７ｇ／１００ｍ１であり、融点が２４０度Ｃ（
分解）である）
有機ゲルマニウム化合物を主成分とし、単独使用も充分
効果があるが、なお、インターフェロン産生剤として知
られる物質と乳糖５０〜８０重景％か重電る組成物によ
り作用増強性の高い安定化組成物が提供されるものであ
る。(Effects of the Invention) In summary, according to the present invention, the white needle is expressed by the following formula: < :aecH2CH2COOH)n01.5n (in the formula, n means an integer of 1 or more) It has a solubility in water of 1.57 g/100ml at 25 degrees Celsius, and a melting point of 240 degrees Celsius (
It has an organic germanium compound as its main component and is sufficiently effective when used alone, but it has a substance known as an interferon-producing agent and a composition containing 50-80% lactose, which enhances its action. A highly stabilized composition is provided.
インターフェロン産生剤として知られる物質にはポリヌ
クレオチド、インフルエンザウィルス、溶連菌、結核菌
、担子菌等の生菌、死菌体成分、酵母細胞壁多糖体等が
あるがエイズ症状発生後は生菌製剤との組成はできるだ
け避け、死菌成分かあるいは本発明ゲルマニウム化合物
と高分子化合物、糖類等の組成の使用が好ましい。Substances known as interferon-producing agents include polynucleotides, influenza virus, live bacteria such as streptococcus, tubercle bacterium, and basidiomycetes, dead bacteria components, and yeast cell wall polysaccharides. It is preferable to avoid the composition as much as possible, and use a composition containing a killed bacteria component or a composition containing the germanium compound of the present invention, a polymer compound, a saccharide, etc.
本発明物質は生体において強力な抗ウィルス作用を有す
るが、その作用機序として体内でのインターフェロン等
の抗ＨＩＶ作用物質の産生の増強が関与している事も示
唆される。The substance of the present invention has a strong antiviral effect in the living body, and it is also suggested that its mechanism of action involves enhancement of the production of anti-HIV active substances such as interferon in the body.
従って本発明組成物はエイズ発症予防剤ないし治療剤と
して極めて有効なものと言える。Therefore, the composition of the present invention can be said to be extremely effective as an agent for preventing or treating the onset of AIDS.
本発明の組成物は、安定性が高く、連続投与が可能であ
り、又継続使用、乃至、投与する事により、安定的な薬
理作用を引出す事が可能である。The composition of the present invention is highly stable and can be administered continuously, and by continuous use or administration, it is possible to elicit stable pharmacological effects.
１、臨床試験結果
ＨＩＶ感染患者６例（血友病患者で年齢６歳〜２２歳い
ずれも男性、Ａｓｙｍｐｔｏｍａｔｉｃ Ｃａｒｒｉｅ
ｒ）うちＨＩＶウィルス陽性４例、ウィルス陰性２例に
対して７ケ月にわたり製剤側記載の本発明製剤を投与し
く有機ゲルマニウム化合物として６０ｍｇ／ １日量、
なお１０歳以下の場合は４０ｍｇ／ １日量）リンパ球
数、０ＫＴ４数、０ＫＴ４／８等の免疫学的検討、血中
のＨＩＶ、ＨＩＶ抗原及びＨＩＶ抗体等のウィルスマー
カー更に臨床的な観察を実施した。リンパ救数は投与前
２４７０±３１１／ＪＪＩ。1. Clinical trial results 6 HIV-infected patients (hemophilia patients, ages 6 to 22, all male, Asymptomatic Carrie
r) Of these, 4 cases were positive for the HIV virus and 2 cases were negative for the virus, and the preparation of the present invention as described in the preparation was administered for 7 months at a daily dose of 60 mg/day as an organic germanium compound.
(For children under 10 years old, 40 mg/day) Immunological examination of lymphocyte count, 0KT4 count, 0KT4/8, etc., viral markers such as HIV in the blood, HIV antigen, and HIV antibody, and clinical observation. carried out. Lymph salvage count was 2470±311/JJI before administration.
投与後６ケ月２３４９±３１２／Ａｌｌと変化は認めら
れなかった。０ＫＴ４は投与前４６３±６４／ｕ１投与
後２ケ月５４９±８９／、ｕｌ、投与後６ケ月６２９±
９７／ｕｌ、増加傾向が認められた。０ＫＴ８は投与後
１３０３±１７４／ｕｌ、投与後６ケ月１１５４±１５
３／Ｊｕｌとやや減少傾向であった０ＫＴ４／８は投与
前０．３６±０．０３．投与後１ケ月０．４２±０．０
２．投与後３ケ月０．５１±０．０６．投与後６ケ月０
．５４±０．０５と漸次上昇傾向が認められた。Six months after administration, it was 2349±312/All, with no change observed. 0KT4 is 463±64/ul before administration, 2 months after administration 549±89/ul, 6 months after administration 629±
97/ul, an increasing trend was observed. 0KT8 was 1303±174/ul after administration, 1154±15 6 months after administration.
0KT4/8, which showed a slight decreasing trend at 3/Jul, was 0.36±0.03 before administration. 1 month after administration 0.42±0.0
2. 0.51±0.06 for 3 months after administration. 6 months after administration
．． A gradual upward trend was observed at 54±0.05.
血中ウィルス分離はＣＤＣ（Ｃｅｎｔｅｒ ｆｏｒ Ｄ
ｉｓｅａ−ｓｅ Ｃｏｎｔｒｏｌ）の方法、ＨＩＶ抗原
はＰ２４のＷｅｓｔｅｒｎ ｂ ｌ ｏｔｔｉｎｇ法
で経日的に測定゛した。Blood virus isolation is carried out by CDC (Center for D
The HIV antigen was measured daily using the P24 Western blotting method.
本発明化合物の６ケ月の投与でＨＩＶ陽性４例の内２例
は変化が見られなか″ったか、２例でＨＩＶの消失が認
められた。（第１表）
一方、臨床的には特に副作用等は認められず、食欲、体
重の増加例が２名に認められた。After 6 months of administration of the compound of the present invention, two of the four HIV-positive cases showed no change or disappearance of HIV in two cases (Table 1).On the other hand, clinically, especially No side effects were observed, and two patients reported an increase in appetite and weight.
（第１表）
ＨＩＶ陽性患者のウィルスマーカーの変化０週 ６ケ
月７ケ月
ＨＩＶ分離 十
患者ＡＨＩ Ｖ抗原
ＨＩＶ分離 十 ＋十−−
患者ＢＨＩＶ抗原士十干十十
２、薬効薬理試験例
■本発明組成物のインフルエンザウィルスによるインタ
ーフェロン産生の増強試験を下記要領で行った。(Table 1) Changes in virus markers of HIV-positive patients 0 weeks 6 months 7 months HIV isolation 10 patients AHIV V antigen HIV isolation 10 + 10-- Patients BHIV antigen specialist 10 and 12, drug efficacy pharmacology test examples ■ This invention A test for enhancing interferon production by influenza virus using the composition was conducted as follows.
ａ）試験方法
ＢＡＬＢ／Ｃ系マウス（］群５匹）にインフルエンザウ
ィルス（Ａ／ＰＲ／８株）を８．７ＰＦＵ／マウスの感
染量で気管内感染させた。感染直後に本発明組成物を本
発明有機ゲルマニウム化合物あたり、０．１ 、 １
、１０．１００ｍｇ／ｋｇで経口投与した。a) Test method BALB/C mice (group 5 mice) were intratracheally infected with influenza virus (A/PR/8 strain) at an infectious dose of 8.7 PFU/mouse. Immediately after infection, the composition of the present invention was administered at a concentration of 0.1 or 1 per organic germanium compound of the present invention.
, 10. Administered orally at 100 mg/kg.
インフルエンザウィルス感染３日後に、マウスの肺を摘
出、ホモジェナイズし、２００００Ｘｇの遠心上清を得
た。その遠心上清のインターフェロン活性を水泡性口炎
ウィルス（ＶＳＶ）によるＬ９２９細胞変性抑制作用で
測定した。Three days after influenza virus infection, the lungs of the mice were removed and homogenized to obtain a supernatant centrifuged at 20,000×g. The interferon activity of the centrifuged supernatant was measured by the inhibitory effect on L929 cell degeneration caused by vesicular stomatitis virus (VSV).
ｂ）結果
結果は第１図にしめす通りであり、本発明による組成物
は主成分である有機ゲルマニウム化合物あたり、１ 、
１０．１００ｍｇ／ｋｇノ投与量で、それぞれ２．２．
２．５及び１．７倍にインターフェロン産生を増強させ
る作用が認められた。b) Results The results are as shown in Figure 1, and the composition according to the present invention contains 1.
10. At a dose of 100 mg/kg, respectively 2.2.
The effect of enhancing interferon production by 2.5 and 1.7 times was observed.
Ｃ）本発明組成物により産生増強したインターフェロン
型の決定。C) Determination of interferon types whose production was enhanced by the composition of the present invention.
本発明組成物投与インフルエンザウィルス感染マウスの
血清を抗マウスα／β−インターフェロン抗体、抗マウ
スβ−インターフェロン抗体及び抗マウスγ−インター
フェロン抗体で４°Ｃ１１時間処理した後、インターフ
ェロン活性を測定した。その結果抗マウスα／β−イン
ターフェロン抗体で処理すると、本発明組成物投与イン
フルエンザウィルス感染マウス血清のインターフェロン
活性は消失したが、抗マウスβ−インターフェロン抗体
及び抗マウスγ−インターフェロン抗体で処理しても活
性消失はみられなかった。以上より本発明組成物によっ
て産生増強したインフルエンザウィルス感染マウスのイ
ンターフェロンはα型である事が強く示唆された。The serum of influenza virus-infected mice administered with the composition of the present invention was treated with anti-mouse α/β-interferon antibodies, anti-mouse β-interferon antibodies, and anti-mouse γ-interferon antibodies at 4°C for 11 hours, and then interferon activity was measured. As a result, when treated with anti-mouse α/β-interferon antibody, the interferon activity of the serum of influenza virus-infected mice administered with the composition of the present invention disappeared, but even when treated with anti-mouse β-interferon antibody and anti-mouse γ-interferon antibody, No loss of activity was observed. From the above, it was strongly suggested that the interferon of influenza virus-infected mice whose production was enhanced by the composition of the present invention was α type.
■ＢＣＧワクチン惑作マウスのインターフェロン産生増
強作用
ａ）試験方法
Ｃ５７ＢＬ／６系マウスを、−群７匹で使用した。乾燥
ＢＣＧワクチンを０．９％生理食塩水に懸濁し、ｏ、２
５ｍｇ／マウスで尾静脈より、静注、感作した。感作１
０日目上り、４日間本発明組成物を、主成分である有機
ゲルマニウムあたり０．１．１ 、１０．１００ｍｇ／
ｋｇで経口投与した。最終投与の翌日（感作１４日後）
にＢＣＧを０．１ｍｇ／マウスで靜注し、３時間後に採
血し、分離した血清のインターフェロン活性を測定した
。(2) Enhancing effect on interferon production in BCG vaccine-stimulated mice a) Test method C57BL/6 mice were used in the - group (7 mice). Dry BCG vaccine was suspended in 0.9% saline, o, 2
Sensitization was carried out by intravenously injecting 5 mg/mouse into the tail vein. Sensitization 1
From day 0 onwards, the composition of the present invention was administered at a concentration of 0.1.1 and 10.100 mg per organic germanium, which is the main component, for 4 days.
kg was administered orally. The day after the final administration (14 days after sensitization)
BCG was injected at 0.1 mg/mouse, blood was collected 3 hours later, and the interferon activity of the separated serum was measured.
ｂ）結果
本発明による組成物は第２図に示すようにＢＣＧ感作マ
ウスのインターフェロン産生を有意に増強し、主成分で
ある有機ゲルマニウムあたり、１．０ｍｇ／ｋｇの投与
量でコントロール群の３．７倍、 １０．０ｍｇ／ｋｌ
Ｊで５．０倍に、インターフェロン産生を増強させる作
用が認められた。b) Results As shown in Figure 2, the composition according to the present invention significantly enhanced interferon production in BCG-sensitized mice, and at a dose of 1.0 mg/kg of organic germanium, the main component, 3 in the control group. .7 times, 10.0mg/kl
The effect of enhancing interferon production by 5.0 times was observed in J.
Ｃ）本発明組成物によって、産生増強したＢＣＧ惑作マ
ウスインターフェロンの型決定。C) Determination of the type of BCG-stimulated mouse interferon whose production was enhanced by the composition of the present invention.
本発明組成物投与ＢＣＧ感作マウスの血清をｐＨ２，０
の０．ＩＨｇ １ｙｓｉｎ−ＨＣＩ ｂｕｆｆｅｒで
２４時間透析後インターフェロン活性を測定した。The serum of BCG-sensitized mice administered with the composition of the present invention was adjusted to pH 2.0.
0. Interferon activity was measured after dialysis with IHg lysin-HCI buffer for 24 hours.
その結果本発明組成物投与ＢＣＧ感作マウス血清のイン
ターフェロン活性は失活した。一方、同様に処理した標
準のα／β−インターフェロンは２２％の活性低下が見
られるのみであった。As a result, the interferon activity of the serum of BCG-sensitized mice administered with the composition of the present invention was inactivated. On the other hand, standard α/β-interferon treated in the same manner showed only a 22% decrease in activity.
ＢＣＧ感作マウスはγ−インターフェロンを産生ずる事
が知られている。以上より本発明組成物投与によって、
産生増強したＢＣＧ感作マウスのインターフェロンはγ
型である事が判明した。BCG-sensitized mice are known to produce γ-interferon. From the above, by administering the composition of the present invention,
Interferon in BCG-sensitized mice with enhanced production is γ.
It turned out to be a type.
ＨＰ Ｃ−Ｌ ２．７ｍ（
１（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 １．８ｍｇ１カプセ
ルあたり １８０ｍｇHP C-L 2.7m (
1 (Hydroxypropylcellulose) Magnesium stearate 1.8mg 180mg per capsule
第１図は本発明組成物によるインフルエンザウィルス感
染マウスのインターフェロン産生増強作用の実験結果を
示すグラフである。
第２図は本発明組成物によるＢＣＧ感染マウスのインタ
ーフェロン産生増強作用の実験結果を示すグラフである
。
特許出願人 株式会社 三和化学研究所第１図
本発明組成物によるインフルエンザウィルス感染マウス
のインターフェロン産生増強作用＊光哩誠物（’）／に
２）FIG. 1 is a graph showing the experimental results of the effect of the composition of the present invention on enhancing interferon production in mice infected with influenza virus. FIG. 2 is a graph showing the experimental results of the effect of the composition of the present invention on enhancing interferon production in BCG-infected mice. Patent applicant: Sanwa Kagaku Institute Co., Ltd. Figure 1: Enhancement of interferon production in mice infected with influenza virus by the composition of the present invention *Mitsuya Seishin (')/ni2)
Claims (1)
れ、白色針状結晶有し、水に対する溶解度が２５度Ｃに
おいて、１．５７ｇ／１００ｍｌであり、融点が２４０
度Ｃ（分解）である有機ゲルマニウム化合物を主成分と
するエイズ治療剤。 ［２］エイズ発症防止効果を有する請求項１記載のエイ
ズ治療剤。 ［３］請求項１記載の有機ゲルマニウム化合物と作用活
性化担体からなるエイズ治療用組成物。 ［４］作用活性化担体がインターフェロン産生物質、糖
類、製剤用高分子性単体から選択される１種類以上から
選択される請求項２記載のエイズ治療用組成物。[Claims] [1] It is represented by a demonstrative formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (in the formula, n means an integer of 1 or more), has white needle-like crystals, Its solubility is 1.57 g/100 ml at 25 degrees C, and its melting point is 240
An AIDS treatment agent whose main ingredient is an organic germanium compound with grade C (decomposition). [2] The AIDS therapeutic agent according to claim 1, which has an effect of preventing the onset of AIDS. [3] A composition for treating AIDS, comprising the organogermanium compound according to claim 1 and an action-activating carrier. [4] The composition for treating AIDS according to claim 2, wherein the action-activating carrier is selected from one or more types selected from interferon-producing substances, sugars, and pharmaceutical simple polymers.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63299202A JPH02145517A (en) | 1988-11-27 | 1988-11-27 | Preventive and remedy for crisis of aids and treating composition thereof |
| AU44484/89A AU633525B2 (en) | 1988-11-15 | 1989-11-08 | Enhancers for biosynthetic interferon and compositions containing them as well as preparations for making aids asymptomatic and curing aids and compositions therefor |
| ES89311840T ES2072910T3 (en) | 1988-11-15 | 1989-11-15 | USE OF A COMPOUND CONTAINING ORGANIC GERMANIUM FOR THE MANUFACTURE OF A MEDICINAL PRODUCT FOR THE TREATMENT OF AIDS. |
| DE1989622826 DE68922826T2 (en) | 1988-11-15 | 1989-11-15 | Use of a composition containing organically bound germanium for the manufacture of medicaments for the treatment of AIDS. |
| EP19890311840 EP0369776B1 (en) | 1988-11-15 | 1989-11-15 | Use of a composition containing organic germanium for the manufacture of a medicament for treating AIDS |
| KR1019890017389A KR970005325B1 (en) | 1988-11-27 | 1989-11-27 | Aids-preventing, curing agents and the composition for treating thereof |
| US07/640,750 US5260056A (en) | 1988-11-15 | 1991-01-14 | Composition for enhancing biosynthesis of interferon |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63299202A JPH02145517A (en) | 1988-11-27 | 1988-11-27 | Preventive and remedy for crisis of aids and treating composition thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02145517A true JPH02145517A (en) | 1990-06-05 |
Family
ID=17869467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63299202A Pending JPH02145517A (en) | 1988-11-15 | 1988-11-27 | Preventive and remedy for crisis of aids and treating composition thereof |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPH02145517A (en) |
| KR (1) | KR970005325B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08119874A (en) * | 1994-10-24 | 1996-05-14 | Takumi Sogabe | Production of suppressor of aids virus and cancer cell |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60190714A (en) * | 1984-03-09 | 1985-09-28 | Sanwa Kagaku Kenkyusho:Kk | Drug composition containing organic germanium compound |
| JPS6165819A (en) * | 1984-09-07 | 1986-04-04 | Sanwa Kagaku Kenkyusho:Kk | Drug composition containing organic germanium compound |
-
1988
- 1988-11-27 JP JP63299202A patent/JPH02145517A/en active Pending
-
1989
- 1989-11-27 KR KR1019890017389A patent/KR970005325B1/en active IP Right Grant
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60190714A (en) * | 1984-03-09 | 1985-09-28 | Sanwa Kagaku Kenkyusho:Kk | Drug composition containing organic germanium compound |
| JPS6165819A (en) * | 1984-09-07 | 1986-04-04 | Sanwa Kagaku Kenkyusho:Kk | Drug composition containing organic germanium compound |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08119874A (en) * | 1994-10-24 | 1996-05-14 | Takumi Sogabe | Production of suppressor of aids virus and cancer cell |
Also Published As
| Publication number | Publication date |
|---|---|
| KR970005325B1 (en) | 1997-04-15 |
| KR900007413A (en) | 1990-06-01 |
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