JPH02174724A - Anti-aids virus agent - Google Patents
Anti-aids virus agentInfo
- Publication number
- JPH02174724A JPH02174724A JP1242773A JP24277389A JPH02174724A JP H02174724 A JPH02174724 A JP H02174724A JP 1242773 A JP1242773 A JP 1242773A JP 24277389 A JP24277389 A JP 24277389A JP H02174724 A JPH02174724 A JP H02174724A
- Authority
- JP
- Japan
- Prior art keywords
- factor
- aids virus
- aids
- serum
- virus
- 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
- 241000700605 Viruses Species 0.000 title claims abstract description 11
- 102000003712 Complement factor B Human genes 0.000 claims abstract description 36
- 108090000056 Complement factor B Proteins 0.000 claims abstract description 36
- 208000030507 AIDS Diseases 0.000 claims abstract description 13
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 210000002966 serum Anatomy 0.000 abstract description 17
- 241000725303 Human immunodeficiency virus Species 0.000 abstract description 15
- 230000003449 preventive effect Effects 0.000 abstract description 4
- 102000003886 Glycoproteins Human genes 0.000 abstract 1
- 108090000288 Glycoproteins Proteins 0.000 abstract 1
- 230000000415 inactivating effect Effects 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000003612 virological effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 17
- 239000012085 test solution Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 241000282412 Homo Species 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 235000015278 beef Nutrition 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 230000004154 complement system Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000003760 tallow Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 208000033065 inborn errors of immunity Diseases 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、ファクターＢを有効成分とする抗エイズウィ
ルス剤に関する。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to an anti-AIDS virus agent containing Factor B as an active ingredient.
〈従来技術の説明〉
エイズウィルス（ＨＩＶ ）はヒトのリンパ球細胞に感
染し、後天性ヒト免疫不全症候群、いわゆるエイズ（Ａ
ＩＤＳ）を引き起こすウィルスである。本疾病に対し有
効性を示す化合物としてはアジドチミジン（ＡＺＴ）や
硫酸化多糖体等が知られているが、これらの化合物は副
作用の面や、有効性の面から治療剤としては充分満足で
きるものではない。<Description of Prior Art> AIDS virus (HIV) infects human lymphocytes and causes acquired human immunodeficiency syndrome, so-called AIDS (AIDs).
It is a virus that causes IDS. Azidothymidine (AZT) and sulfated polysaccharides are known to be effective against this disease, but these compounds are not sufficiently satisfactory as therapeutic agents in terms of side effects and efficacy. isn't it.
〈発明が解決しようとする問題点〉
本発明者は前記問題点を解決すべく鋭意検討した結果、
血清の一成分であるファクターＢに抗エイズウイルス作
用を見い出し、本発明を完成した。<Problems to be solved by the invention> As a result of intensive studies to solve the above problems, the inventors have found that:
They discovered that Factor B, a component of serum, has an anti-AIDS virus effect and completed the present invention.
〈発明の構成〉
本発明はファクターＢを有効成分とする抗エイズウィル
ス剤に関する。<Configuration of the Invention> The present invention relates to an anti-AIDS virus agent containing Factor B as an active ingredient.
ファクターＢは、前記の如く血清の一成分であり、その
血清中での濃度は通常２００〜４００μｇ／ｍｌである
。ファクターＢの分子量は、ヒトの場合には約９０，０
００〜約９３，０００前後の穂蛋白であって、糖類を約
１０９６程度その分子中に含んでいる。As mentioned above, Factor B is a component of serum, and its concentration in serum is usually 200 to 400 μg/ml. The molecular weight of Factor B is approximately 90.0 in humans.
It is a panicle protein with a molecular weight of about 00 to about 93,000, and contains about 1096 sugars in its molecule.
本物質は非特異的免疫反応にかかわる補体第二経路のａ
ｌｔｅｒｎａｔｉｖｅ ｐａｔｈｗａｙにあずかる因子
である。本物質の補体系活性（例えば、ＥＳＳＥＮＴＩ
ＡＬＩＭＭｕＮＯＬＯＧＹ 第６版７−９頁、 １５
−１７頁 １９８８年）は般に熱に不安定であり、例え
ば、５６℃前後、約３０分の加温で失なわれる。ヒトの
ファクターＢのアミノ酸配列は、ＥＭＢＯＪｏｕｒｎａ
ｌ ３１５’３−１５７ （１９８４）、 Ｂｉｏｃｈ
ｅｍ、Ｊ、（１９８３） ２０９．５１−６０等に報告
されているが、該配列の一部が欠落したり、又は他のア
ミノ酸と置換したもの、もしくはアミノ酸が付加したも
の、或は前記糖部分が欠落したもの又は糖部分の配列の
一部が欠落したもの、他の糖類に置換されたもの若しく
はｉｌＨ］が付加したもの更には新たなｍ＆Ｒが結合し
たものであってもファクターＢとしての補体系活性を有
するものであれば、それらは本発明の範囲に含まれる。This substance is a component of the alternative complement pathway involved in non-specific immune reactions.
It is a factor that participates in an alternative pathway. Complement system activity of the substance (e.g. ESSENTI
ALIMMuNOLOGY 6th edition pp. 7-9, 15
-17 p. 1988) is generally unstable to heat, and is lost by heating at around 56° C. for about 30 minutes, for example. The amino acid sequence of human factor B is available from EMBOJourna
l 315'3-157 (1984), Bioch
Em. Even if a part is missing, a part of the sequence of the sugar part is missing, something is substituted with another saccharide, or something to which ilH] is added, or a new m&R is attached, it can be used as Factor B. As long as they have complement system activity, they are within the scope of the present invention.
又、ヒト以外の動物由来のファクターＢであってもヒト
のものと同様の活性を呈する場合には本発明の範囲に含
まれるが、通常は副作用の面からヒト由来のファクター
Ｂが望ましい。Although Factor B derived from animals other than humans is included within the scope of the present invention if it exhibits the same activity as that of humans, Factor B derived from humans is usually preferred from the viewpoint of side effects.
ファクターＢは前記の如く血清中の一成分であることか
ら、安全性上の問題は殆どないと考えられ、例えば、ヒ
ト由来の本物質を１００μｇ／ｍ ｌの濃度で培地に添
加し、該培地でリンパ球細胞を培養した場合でも細胞毒
性は全く観察されなかった。Since Factor B is a component in serum as mentioned above, it is thought that there are almost no safety issues.For example, if this human-derived substance is added to a culture medium at a concentration of 100 μg/ml, No cytotoxicity was observed even when lymphocyte cells were cultured.
ファクターＢは通常静脈内に投与され、その投与量は通
常成人−人当り ２〜１０００ｍｇ／日の範囲であり、
患者の症状に応じて適宜増減すればよい。Factor B is usually administered intravenously, and the dosage is usually in the range of 2 to 1000 mg/day per adult.
The dose may be increased or decreased as appropriate depending on the patient's symptoms.
ファクターＢは公知の製剤技術によりアルブミン、裾頚
、アミノ酸の如き安定化剤、等張化剤等の添加剤と共に
注射剤に製剤化することがで参る。Factor B can be formulated into an injection together with additives such as albumin, stabilizers such as amino acids, and tonicity agents using known formulation techniques.
〈発明の効果〉
ファクターＢはエイズウィルスに対し増殖抑制効果及び
不活化効果を有することから、抗エイズウィルス剤とし
て優れたものであり、エイズウィルスのキャリアーの発
症の予防剤並びにエイズ、エイズ関連症候群の予防及び
治療剤として期待しつる。<Effects of the Invention> Since Factor B has the effect of suppressing the proliferation and inactivation of the AIDS virus, it is excellent as an anti-AIDS virus agent, and can be used as a preventive agent for the onset of AIDS virus carriers and for treating AIDS and AIDS-related syndromes. The vine is expected to be used as a preventive and therapeutic agent.
以下、本発明を更に実施例により説明するが、本発明は
これにより限定されるものではない。EXAMPLES Hereinafter, the present invention will be further explained with reference to Examples, but the present invention is not limited thereto.
実施例１
［材料］
１）ウィルスはエイズウィルスのＬＡＶＩ株を、又宿主
リンパ球細胞にはＣＥＭ／Ｃ１１３細胞を用いた。Example 1 [Materials] 1) The LAVI strain of AIDS virus was used as the virus, and CEM/C113 cells were used as the host lymphocytes.
２）培養液は１０を非働化牛脂児血清加ＲＰＭ１１６４
０培地（Ｇｉｂｃｏ社製）を使用した。2) The culture solution is RPM1164 with 10 inactivated beef tallow serum added.
0 medium (manufactured by Gibco) was used.
３）人新鮮血清は自家調製し、ヒトファクターＢ並びに
ファクターＢ欠損ヒト血清はＳｉｇｍａ社より購入した
。ファクターＢを水中で予め１２時間マグネシウムイオ
ン及びカルシウムイオンを含まない１１）ｍｓ！リン酸
バッファ −［ｐＨニア、２．以下、ＰＢＳ （−）と
略すコに対し透析し、 １ｍｇ／ｍｌの割にＰＢＳ（−
）で調整した
［方法コ
３日間前培養した宿主細胞にエイズウィルスをＭＯＩ
Ｏ，０５−０，１の割でチャレンジし、９０分間の吸着
後５Ｘ１０’ ｃｅｌｌ／ｍｌに培養液中に浮遊させ、
その０．５ｍｌ、培養液０．４ｍｌ及び試験液０．１ｍ
ｌを２４穴マルチプレートの一穴中に注いで５ＸＣＯｚ
−９５％１ａｉｒの条件下で培養を開始した。尚、上記
試験液の代わりに生牛脂児血清あるいは培養液０．１ｍ
ｌを添加した穴を対照とした。経日的に生細胞率をトリ
パンブルー排除法で求め、又エイズウィルス抗原陽性前
ｎき率（ＩＦＡ陽性率）については間接蛍光抗体法で求
めた。3) Fresh human serum was prepared in-house, and human factor B and factor B-deficient human serum were purchased from Sigma. Factor B in water for 12 hours without magnesium and calcium ions 11) ms! Phosphate buffer - [pH near, 2. Hereinafter, dialysis was performed against PBS (-), and PBS (-) was used for 1 mg/ml.
) [Method] Inject AIDS virus into host cells precultured for 3 days at MOI.
Challenged at a ratio of O.
0.5ml of that, 0.4ml of culture solution and 0.1ml of test solution
Pour l into one hole of a 24-well multi-plate and add 5X COz
Culture was started under -95% 1air conditions. In addition, instead of the above test solution, use raw beef tallow serum or 0.1 m culture solution.
The wells to which L was added served as a control. The percentage of viable cells was determined over time by the trypan blue exclusion method, and the AIDS virus antigen positive rate (IFA positive rate) was determined by the indirect fluorescent antibody method.
［結果］
１）試験液としてファクターＢ欠損血清（試験液Ａ）又
はファクターＢを添加したファクターＢ欠損血清（ファ
クターＢ添加量；２５μｇ／ｍｌ、試験液８）を用いた
場合の結果を表１に示した。[Results] 1) Table 1 shows the results when factor B-deficient serum (test solution A) or factor B-deficient serum to which factor B was added (factor B addition amount: 25 μg/ml, test solution 8) was used as the test solution. It was shown to.
上表から明らかなように、ファクターＢ欠損血清を培養
液に添加した場合には対照と同様に培養細胞の生細胞率
は低下し、且つＩＦＡ陽性率は低下しなかった。しかし
ながら、ファクターＢを該血清に添加することにより生
細胞率の低下が阻止され且つｕＡ陽性率が低下したこと
から、細胞の再増殖が見られた。As is clear from the above table, when Factor B-deficient serum was added to the culture solution, the viable cell rate of the cultured cells decreased, similar to the control, and the IFA positive rate did not decrease. However, addition of Factor B to the serum prevented the decrease in viable cell rate and decreased the uA positive rate, indicating that cells repopulated.
２）試験液として、エイズウィルス感染後の細胞再増殖
時期が常に遅い血清（試験液Ｃ）及び該血清にファクタ
ーＢを添加したもの（ファクターＢ添加量：２５μ ｇ
／ ｍ １ 、試験液Ｄ）を用いた場合の結果を表２に
示した。2) Test solutions include serum whose cell regrowth period is always slow after infection with the AIDS virus (test solution C), and serum to which Factor B has been added (amount of Factor B added: 25 μg)
/ m 1 , and the results when using test solution D) are shown in Table 2.
尚、試験液Ｃではプロパジーン活性の低下がみられたこ
とから補体第二経路の機能低下が見られた。In Test Solution C, a decrease in propagene activity was observed, indicating a decrease in the function of the alternative complement pathway.
上表から明らかなように、ウィルス感染後の細胞再増殖
時期が常に遅い血清にファクターＢを添加することによ
り細胞の再増殖時期を速めることかできた。As is clear from the above table, by adding Factor B to serum, which always has a slow cell repopulation time after virus infection, it was possible to accelerate the cell repopulation time.
３）試験液としてファクターＢを添加した培養液（ファ
クターＢ添加Ｅｋ ： １２．５μｇ／ｒｎｌ、試験液
Ｅ）を用いた場合の結果を表３に示した。3) Table 3 shows the results when a culture solution to which Factor B was added (Factor B addition Ek: 12.5 μg/rnl, Test Solution E) was used as the test solution.
上記表３から明らかなように、ファクターＢを培地中に
添加することにより細胞の生細胞率の低下が抑制され、
且つ細胞のＩＦＡ陽性率が低下したことからファクター
Ｂの添加により細胞の再増殖が見られた。As is clear from Table 3 above, adding Factor B to the medium suppresses the decrease in cell viability,
Furthermore, since the IFA positive rate of the cells decreased, repopulation of the cells was observed due to the addition of Factor B.
以上の結果からファクターＢがエイズウィルスに対し増
殖抑制効果を有することが確誌された。From the above results, it was confirmed that Factor B has a growth inhibiting effect on the AIDS virus.
実施例２ ［材料］ 実施例１と同じ。Example 2 [material] Same as Example 1.
［方法コ
ファクターＢの調製液０．２ｍｌとエイズウィルス液（
５ｘｌＯ’ＴＣＩＤ５ｏ／ｍｌ） ０．２ｍｌとを混和
し、３７℃で３０分間保ったのちＰＢＳ（−）で１００
００倍稀釈した（試験液Ｆ）、又、ＰＢＳ （−）及び
ウィルス液を試験液と同様に混合及び希釈し、これを対
照として用いた。[Method 0.2 ml of cofactor B preparation and AIDS virus solution (
5xlO'TCID5o/ml) was mixed with 0.2ml, kept at 37℃ for 30 minutes, and diluted with PBS(-) for 100 minutes.
00 times diluted (test solution F), and PBS (-) and virus solution were mixed and diluted in the same manner as the test solution and used as a control.
試験液又は対照液の０．１＋ｎｌを１ｘｌＯ６／個のＣ
ＥＭ／Ｃ１１３細胞と合せて９０分間吸着させ、２．５
ｘｌＯ’ｃｅｌｌ／ｍｌに調整したあと、その１ｍｌを
２４穴マルチプレートへ分注して培養を開始した。経日
的に生細胞率及びＩＦＡ陽性率を求めた。0.1+nl of test solution or control solution to 1xlO6/C
Adsorb with EM/C113 cells for 90 minutes,
After adjusting to xlO'cell/ml, 1 ml was dispensed into a 24-well multi-plate to start culturing. The viable cell rate and IFA positive rate were determined over time.
［結果コ 結果を表４に示した。[Result The results are shown in Table 4.
表４
上表から、対照では経口的に生細胞率が低下し、且つＩ
ＦＡＩＩＩ性率が上昇することからエイズウィルスが細
胞に感染し、細胞中で増殖していることが明らかとなる
。これに対し、あらかじめエイズウィルスをファクター
Ｂで処理した試験では生細胞率の低下及びＩＦＡの陽性
率の上昇は抑制された。従って、ファクターＢは単独で
エイズウィルスの感染性を中和する能力を有し、抗エイ
ズウィルス剤として有用であることが確認された。Table 4 From the above table, the viable cell rate decreased in the control and the I
The increase in the FAIII sex rate indicates that the AIDS virus is infecting cells and proliferating within them. On the other hand, in a test in which the AIDS virus was treated with Factor B in advance, the decrease in the viable cell rate and the increase in the IFA positivity rate were suppressed. Therefore, it was confirmed that Factor B alone has the ability to neutralize the infectivity of the AIDS virus and is useful as an anti-AIDS virus agent.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1242773A JPH02174724A (en) | 1988-09-19 | 1989-09-19 | Anti-aids virus agent |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63-234380 | 1988-09-19 | ||
| JP23438088 | 1988-09-19 | ||
| JP1242773A JPH02174724A (en) | 1988-09-19 | 1989-09-19 | Anti-aids virus agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02174724A true JPH02174724A (en) | 1990-07-06 |
Family
ID=26531539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1242773A Pending JPH02174724A (en) | 1988-09-19 | 1989-09-19 | Anti-aids virus agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02174724A (en) |
-
1989
- 1989-09-19 JP JP1242773A patent/JPH02174724A/en active Pending
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