JPH0577649B2 - - Google Patents
Info
- Publication number
- JPH0577649B2 JPH0577649B2 JP1292464A JP29246489A JPH0577649B2 JP H0577649 B2 JPH0577649 B2 JP H0577649B2 JP 1292464 A JP1292464 A JP 1292464A JP 29246489 A JP29246489 A JP 29246489A JP H0577649 B2 JPH0577649 B2 JP H0577649B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- formula
- compounds
- compound
- tablets
- 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 - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 15
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
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- 239000003903 antiretrovirus agent Substances 0.000 claims description 5
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- 239000000126 substance Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 description 21
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 241001430294 unidentified retrovirus Species 0.000 description 10
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- 238000005469 granulation Methods 0.000 description 1
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- AIONOLUJZLIMTK-AWEZNQCLSA-N hesperetin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-AWEZNQCLSA-N 0.000 description 1
- 229960001587 hesperetin Drugs 0.000 description 1
- AIONOLUJZLIMTK-UHFFFAOYSA-N hesperetin Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(O)=CC(O)=C2C(=O)C1 AIONOLUJZLIMTK-UHFFFAOYSA-N 0.000 description 1
- 235000010209 hesperetin Nutrition 0.000 description 1
- FTODBIPDTXRIGS-UHFFFAOYSA-N homoeriodictyol Natural products C1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 FTODBIPDTXRIGS-UHFFFAOYSA-N 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000008164 mustard oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 235000005875 quercetin Nutrition 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Description
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矀ïŒAIDSïŒãåŒãèµ·ãããHIVïŒHuman
Immuno deficiency VirusïŒãHTLVâïŒæ人
现èçœè¡çãŠã€ã«ã¹ïŒçã¯ã¬ãããŠã€ã«ã¹ãšã
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èš±åºé¡ããŠããïŒç¹é¡æå62幎第321516å·ãç¹é¡
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[Industrial Field of Application] The present invention relates to an antiretroviral agent effective in treating various viral diseases caused by retroviruses. [Prior Art and Problems] As research on viruses continues, treatments for viral diseases are gradually being established. HIV (Human
Immuno deficiency virus), HTLV-I (adult T-cell leukemia virus), and the like are known as retroviruses. Retroviruses contain RNA inside their virus particles.
dependent DNA synthase (hereinafter referred to as reverse transcriptase)
It is a virus containing After infecting a host cell, RNA is first transcribed into DNA by reverse transcriptase. This DNA is integrated into the host cell chromosome,
then by host cell RNA synthase
mRNA is synthesized. Various viral proteins are produced from this mRNA. There has been a desire to develop a drug that has an epoch-making therapeutic effect on human diseases caused by this retrovirus. [Means for Solving the Problems] The present inventors conducted research on the retrovirus growth inhibitory effect of various herbal medicines, and found that baicalein and baicalin were extracted and isolated from the herbal medicine yellow, and quercetin was extracted and isolated from Caica. They also discovered that hesperetin extracted and isolated from Chinpi had a retrovirus growth inhibiting effect, and filed patent applications (Patent Application No. 321516 of 1982, Patent Application No. 321517 of 1988, and Patent Application No. 321517 of 1988). No. 321518). By continuing this research, we have developed the following formula:
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ããªãã¡æ¬çºæã¯ãäžèšåŒ[Chemical formula] (In the formula, R 1 represents a hydrogen atom, a hydroxyl group, -O-rhamnoside, or -O-rutinoside, and R 2 , R 3 ,
R 4 , R 5 , R 6 and R 7 represent a hydrogen atom or a hydroxyl group. However, compounds in which R 1 , R 4 , R 5 , R 6 and R 7 are hydrogen atoms, R 2 and R 3 are hydroxyl groups, and R 4 and R 7 are hydrogen atoms, R 1 , R 2 ,
Excludes compounds in which R 3 , R 5 and R 6 are hydroxyl groups. The present inventors have discovered that the compound represented by the following formula and digalic acid have an inhibitory effect on the growth of retroviruses, and have completed the present invention. That is, the present invention provides the following formula
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ããã[Chemical formula] (In the formula, R 1 represents a hydrogen atom, a hydroxyl group, -O-rhamnoside, or -O-rutinoside, and R 2 , R 3 ,
R 4 , R 5 , R 6 and R 7 represent a hydrogen atom or a hydroxyl group. However, compounds in which R 1 , R 4 , R 5 , R 6 and R 7 are hydrogen atoms, R 2 and R 3 are hydroxyl groups, and R 4 and R 7 are hydrogen atoms, R 1 , R 2 ,
Excludes compounds in which R 3 , R 5 and R 6 are hydroxyl groups. ) This is an antiretroviral agent containing the compound represented by the formula and digaluc acid (hereinafter, the compound represented by the formula and digalic acid are collectively referred to as the compound of the formula) as active ingredients. It has not been previously known that the compound of the formula has an antiviral effect, particularly an antiretroviral effect. Specific examples of compounds of the formula are as follows, and commercially available compounds can be used.
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M.NishizawaïŒT.YamagishiïŒG.Nonaka
and I.NishiokaïŒJ.Chem.Soc.Perkin Trans.ïŒïŒ
2963ïŒ1982
次ã«ãåŒã®ååç©ãæã¬ãããŠã€ã«ã¹å¹æãæ
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èãå¹é€ããäžå³¶çã®æ¹æ³ïŒ»CONPARATIVE
LEUKEMIA RESEARCH 1973ïŒ
LEUKEMOGENESISïŒED.Y.ITO.AND R.M.
DUTCHERïŒUNIV.OF TOKYO PRESS
TOKYOïŒKARGERïŒBASELïŒPP.603â605
ïŒ1975ïŒïŒœã«æºæ ããŠãé転åé
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Îãžããªã¹ã¬ã€ããŒã« 5mM
Îå¡©åã«ãªãŠã 50mM
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ž 0.01mM
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ãã®çµæã第ïŒè¡šã«ç€ºãã[Table] For example, Dzigaricum can be isolated from plants as follows. In other words, plants containing snails,
Extraction is performed using one or more mixed solvents selected from water, methanol, ethanol, acetone, and ethyl acetate. It can be obtained by subjecting it at least once to column chromatography using a porous polymer gel such as CHP20P as a carrier. Jigali Tsukashi refers to two types of Jigali Tsukashi: meta-Jigali Tsukashi and para-Jigali Tsukashi.
There are two isomers, which interconvert in solution. The ginger acid according to the present invention comprises:
Contains meta-digalidic acid, para-digalidic acid and mixtures of both compounds in any proportion. A specific example of the production of liquid acid is shown below. Specific example: Extract 5 kg of Chinquapin leaves three times with 40 parts water-acetone (1:4) mixture, concentrate the extract (distill off acetone), extract the aqueous layer with 1 part ethyl acetate, and extract with ethyl acetate. The liquid was concentrated and dried to obtain 200 g of extract. Use this extract as Cephadex LH.
-20 column chromatography,
Elution was carried out by sequentially changing the mixing ratio of water and methanol. Mixing ratio of water and methanol is 1:1 to 3:7
The eluate was concentrated and dried to obtain a crude fraction. This crude fraction was subjected to column chromatography using Sephadex LH-20 using ethanol, water-methanol (1:4) as an eluent. Then water-
The eluate was subjected to column chromatography using MCI-gel CHP20P using a solvent in which the mixing ratio of methanol was successively changed, and the eluate was concentrated at a water-methanol mixing ratio of 4:1 to 7:3. By drying, meta-digger acid (m-
460 mg of digallic acid was obtained. The physicochemical properties of the meta-digaric acid obtained as described above were consistent with the literature values shown below. [M.Nishizawa, T.Yamagishi, G.Nonaka
and I.Nishioka, J.Chem.Soc.Perkin Trans. 1 ,
2963, 1982] Next, the fact that the compound of the formula has an antiretroviral effect will be explained with reference to experimental examples. Experimental example: Cells infected with murine leukemia virus (Lauchier strain) were cultured, and the method of Nakajima et al. [CONPARATIVE
LEUKEMIA RESEARCH 1973,
LEUKEMOGENESISïŒED.Y.ITO.AND RM
DUTCHER, UNIV.OF TOKYO PRESS
TOKYO/KARGER, BASEL, PP.603â605
(1975)], reverse transcriptase was isolated and purified. Next, a reaction mixture having the following composition was prepared. Î reverse transcriptase 1 unit/ml Î polyadenylic acid/oligothymidylic acid complex as Î template/primer complex [polyadenylic acid (manufactured by Pharmacia): oligothymidylic acid (manufactured by Pharmacia) = 4:1] 2 ÎŒg/ml Î Tris-HCl (PH8.0) 50mM Îdithiothreitol 5mM Îpotassium chloride 50mM Îmanganese chloride 0.2mM Î[ 3H ]deoxythymidine triphosphate 0.01mM (hereinafter abbreviated as [ 3H ]dTTP)
(400cpm/pmol) ÎGlycerol 15 (v/v)% ÎPurified water Appropriate amount *1 unit means that reverse transcriptase is
It is a specific activity unit that consumes 1 nmol of dNTD (deoxynucleic acid triphosphate). Add 20Ό of this reaction mixture to
Add the compound of formula and purified water to make 50Ό,
The incorporation of radioactivity into the acid-insoluble fraction of [ 3 H]dTTP was measured using a Beckman scintillation counter to determine reverse transcriptase activity, and the inhibition rate at each concentration was calculated. The results are shown in Table 1.
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ãè¡ã€ãŠæ³šå°å€ãåŸãã[Table] The above results confirmed the excellent antiretroviral effect of the compound of formula. As mentioned above, the compound of the formula has the effect of suppressing the proliferation of retroviruses by inhibiting the reverse transcriptase activity necessary for their proliferation, so it can be applied to any retrovirus. I can do it. Specific examples of retroviruses include leukemia virus, sarcoma virus, breast cancer virus, Visna virus, Maedi virus, HIV, HTLV-I, and the like. Next, we conducted an acute toxicity test of oral administration of the compound of formula in ddY male mice and Wistar.
When the test was carried out using male rats, there were no deaths even when the compound of the formula was orally administered at 1 g/Kg. Thus, the compound of the formula has extremely low toxicity and high safety. Next, the dosage and formulation of compounds of formula will be described. The compounds of the formula can be administered to animals and humans neat or with conventional pharmaceutical carriers. The dosage form is not particularly limited and may be selected and used as necessary, and may include oral dosage forms such as tablets, capsules, granules, fine granules, and powders, and parenteral dosage forms such as injections and suppositories. It will be done. In order to exert the desired effect as an oral agent,
Although it varies depending on the patient's age, weight, and severity of the disease,
Normally for adults, the weight of the compound of formula is 100 mg to 6 g.
It seems appropriate to take the drug in divided doses several times a day. In the present invention, oral preparations such as tablets, capsules, and granules are manufactured according to conventional methods using, for example, starch, lactose, sucrose, mannitol, carboxymethyl cellulose, cornstarch, inorganic salts, and the like. In addition to the above-mentioned excipients, binders, disintegrants, surfactants, lubricants, fluidity promoters, flavoring agents, coloring agents, perfumes, and the like can be used in this type of preparation as appropriate. Specific examples of each are shown below. [Binder] Starch, dextrin, gum arabic powder, gelatin, hydroxypropyl starch, methylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, ethylcellulose, polyvinylpyrrolidone, macrogol. [Disintegrant] Starch, hydroxypropyl starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, low substituted hydroxypropyl cellulose. [Surfactant] Sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 80. [Lubricant] Talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate,
Polyethylene glycol. [Fluidity promoter] Light anhydrous silicic acid, dry aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate. Furthermore, the antiretroviral agent of the present invention can be administered as a suspension, emulsion, syrup, or elixir, and these various dosage forms may contain flavorings and coloring agents. good. In order to exert the desired effect as a parenteral agent, it is usually necessary for an adult to take 1 to 10% of the weight of the compound of the formula per day, although it varies depending on the age, weight, and severity of the disease of the patient.
Intravenous injections, intravenous drips, subcutaneous injections, and intramuscular injections of up to 100 mg are considered appropriate. This parenteral preparation is manufactured according to a conventional method, and diluents generally include distilled water for injection, physiological saline, aqueous glucose solution, vegetable oil for injection, sesame oil, mustard oil, soybean oil, corn oil, propylene glycol, polyethylene glycol, etc. can be used. Furthermore, a bactericide, a preservative, and a stabilizer may be added as necessary. In addition, from the standpoint of stability, this parenteral preparation is frozen after being filled into vials, etc.
The liquid formulation can also be reconstituted from the lyophilizate immediately prior to use by removing moisture by conventional lyophilization techniques. Furthermore, isotonizing agents, stabilizers, preservatives, soothing agents, etc. may be added as appropriate. Other parenteral preparations include liquid preparations for external use, liniments such as ointments, suppositories for rectal administration, and the like, which are manufactured according to conventional methods. Example 1 Corn starch 44g Crystalline cellulose 40g Carboxymethyl cellulose calcium
5 g Light anhydrous silicic acid 0.5 g Magnesium stearate 0.5 g Luteolin 10 g Total 100 g According to the above recipe, - were mixed uniformly and compressed using a tablet machine to obtain tablets each weighing 200 mg. One tablet of this tablet contains 20 mg of luteolin, and adults should take 5 to 7 tablets a day in several doses. Example 2 Crystalline cellulose 84.5g Magnesium stearate
0.5 Carboxymethyl cellulose calcium
5g morin 10g total 100g According to the above recipe, a part of and was mixed uniformly, compressed and molded, then crushed, the remaining amount of and was added and mixed, and compressed and molded using a tablet machine. Tablets of 200 mg were obtained. One tablet of this tablet contains 20 mg of morin, and adults should take 5 to 7 tablets a day in several doses. Example 3 Crystalline cellulose 34.5g 10% hydroxypropylcellulose ethanol solution 50g Carboxymethylcellulose calcium
5 g Magnesium stearate 0.5 g Quercitrin 10 g Total 100 g According to the above recipe, and are mixed uniformly, and are netted by a conventional method, granulated with an extrusion granulator, dried and crushed, and then The mixture was mixed and compressed using a tablet machine to obtain tablets each weighing 200 mg. Each tablet contains 20 mg of quercitrin, and adults should take 5 to 7 tablets a day in several doses. Example 4 Cornstarch 84g Magnesium stearate 0.5g Carboxymethyl cellulose calcium
5g Light anhydrous silicic acid 0.5g Rutin 10g Total 100g According to the above recipe, mix ~ uniformly, compress it with a compression molding machine, then crush it with a crusher,
Granules were obtained by sieving. 1 g of this granule contains 100 mg of rutin, and adults should take 1 to 2.5 g per day in several doses. Example 5 Crystalline cellulose 40 g 10% hydroxypropyl cellulose ethanol solution 50 g Quercetagetin 10 g Total 100 g According to the above recipe, ~ were mixed uniformly and were suspended. After granulation using an extrusion granulator, the mixture was dried and sieved to obtain granules. 1 g of this granule contains 100 mg of quercetagetin, and adults should take 1 to 2.5 g per day in several doses. Example 6 Cornstarch 89.5g Light anhydrous silicic acid 0.5g Myricetin 10g Total 100g Mix ~ uniformly according to the above recipe,
200 mg was filled into No. 2 capsules. Each capsule contains 20 mg of myricetin.
It contains 5 to 7 capsules per day for adults, divided into several doses. Example 7 Corn starch 44g Crystalline cellulose 40g Carboxymethyl cellulose calcium
5 g Light anhydrous silicic acid 0.5 g Magnesium stearate 0.5 g Digalic acid 10 g Total 100 g According to the above recipe, - were mixed uniformly and compressed using a tablet machine to obtain tablets each weighing 200 mg. One tablet of this tablet contains 20 mg of digaric acid, and adults should take 5 to 7 tablets a day in several doses. Example 8 Distilled water for injection Appropriate amount Glucose 200 mg 6,7-dihydroxyflavone 10 mg Total amount 15 ml After dissolving and in distilled water for injection, 5
The mixture was injected into a ml ampoule and autoclaved at 121°C for 15 minutes to obtain an injection.
Claims (1)
ãããŸãã¯ââã«ããã·ãã瀺ããR2ãR3ã
R4ãR5ãR6ããã³R7ã¯æ°ŽçŽ ååãŸãã¯æ°Žé žåºã
瀺ãã ãã ããR1ãR4ãR5ãR6ããã³R7ãæ°ŽçŽ åå
ã§ãããR2ããã³R3ãæ°Žé žåºã§ããååç©ãªã
ã³ã«R4ããã³R7ãæ°ŽçŽ ååã§ãããR1ãR2ã
R3ãR5ããã³R6ãæ°Žé žåºã§ããååç©ãé€ããïŒ ã§è¡šãããååç©ãæå¹æåãšããæã¬ãããŠã€
ã«ã¹å€ã ïŒ ãžã¬ãªãã¯ã¢ã·ãããæå¹æåãšããæã¬ã
ããŠã€ã«ã¹å€ã[Claims] 1 The following formula [Chemical formula] (wherein R 1 represents a hydrogen atom, a hydroxyl group, -O-rhamnoside, or -O-rutinoside, and R 2 , R 3 ,
R 4 , R 5 , R 6 and R 7 represent a hydrogen atom or a hydroxyl group. However, compounds in which R 1 , R 4 , R 5 , R 6 and R 7 are hydrogen atoms, R 2 and R 3 are hydroxyl groups, and R 4 and R 7 are hydrogen atoms, R 1 , R 2 ,
Excludes compounds in which R 3 , R 5 and R 6 are hydroxyl groups. ) An antiretroviral agent whose active ingredient is a compound represented by 2.An antiretroviral agent containing zigaric acid as an active ingredient.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1292464A JPH037224A (en) | 1989-03-08 | 1989-11-13 | Anti-retrovirus agent |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP5390789 | 1989-03-08 | ||
JP1-53907 | 1989-03-08 | ||
JP1292464A JPH037224A (en) | 1989-03-08 | 1989-11-13 | Anti-retrovirus agent |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH037224A JPH037224A (en) | 1991-01-14 |
JPH0577649B2 true JPH0577649B2 (en) | 1993-10-27 |
Family
ID=12955789
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP1292464A Granted JPH037224A (en) | 1989-03-08 | 1989-11-13 | Anti-retrovirus agent |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH037224A (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE59309337D1 (en) * | 1992-07-03 | 1999-03-11 | Alfatec Pharma Gmbh | Solid and liquid solutions of flavonoids |
US5298148A (en) * | 1993-02-23 | 1994-03-29 | Kansai Paint Co., Ltd. | Electrodeposition paint compositions |
JPH0725761A (en) | 1993-07-09 | 1995-01-27 | Kureha Chem Ind Co Ltd | Agent for protecting cartilage |
JP2003504327A (en) * | 1999-07-08 | 2003-02-04 | ãã¬ã³ããŒã¬ã¹ãããããªãã¯ããã£ïŒ | Use of flavones, coumarins and related compounds for the treatment of infectious diseases |
CN104906058B (en) * | 2015-06-05 | 2017-10-03 | å京æ£å€§å€©æŽå¶è¯æéå ¬åž | A kind of diosmin tablet and its preparation technology |
CN108383821A (en) * | 2018-05-03 | 2018-08-10 | äºåå€§åŠ | Methoxyl group -7- cyanidenons and its preparation method and application |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01163122A (en) * | 1987-12-21 | 1989-06-27 | Tsumura & Co | Anti-retrovirus agent |
JPH01163120A (en) * | 1987-12-21 | 1989-06-27 | Tsumura & Co | Anti-retrovirus agent |
JPH01163121A (en) * | 1987-12-21 | 1989-06-27 | Tsumura & Co | Anti-retrovirus agent |
-
1989
- 1989-11-13 JP JP1292464A patent/JPH037224A/en active Granted
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01163122A (en) * | 1987-12-21 | 1989-06-27 | Tsumura & Co | Anti-retrovirus agent |
JPH01163120A (en) * | 1987-12-21 | 1989-06-27 | Tsumura & Co | Anti-retrovirus agent |
JPH01163121A (en) * | 1987-12-21 | 1989-06-27 | Tsumura & Co | Anti-retrovirus agent |
Also Published As
Publication number | Publication date |
---|---|
JPH037224A (en) | 1991-01-14 |
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