FR2648047A2 - Polyphenolic product having antiviral activity - Google Patents

Polyphenolic product having antiviral activity Download PDF

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Publication number
FR2648047A2
FR2648047A2 FR8907654A FR8907654A FR2648047A2 FR 2648047 A2 FR2648047 A2 FR 2648047A2 FR 8907654 A FR8907654 A FR 8907654A FR 8907654 A FR8907654 A FR 8907654A FR 2648047 A2 FR2648047 A2 FR 2648047A2
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France
Prior art keywords
product
procyanidols
soluble
patent application
viral
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Application number
FR8907654A
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French (fr)
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FR2648047B2 (en
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Individual
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Individual
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Publication date
Priority claimed from FR8906282A external-priority patent/FR2646852B1/en
Application filed by Individual filed Critical Individual
Priority to FR8907654A priority Critical patent/FR2648047B2/en
Priority to PCT/FR1990/000200 priority patent/WO1990013304A1/en
Priority to CA002057023A priority patent/CA2057023A1/en
Priority to DK90905558.4T priority patent/DK0472531T3/en
Priority to DE69021725T priority patent/DE69021725T2/en
Priority to AT90905558T priority patent/ATE126439T1/en
Priority to ES90905558T priority patent/ES2078339T3/en
Priority to AU54000/90A priority patent/AU648754B2/en
Priority to JP2505329A priority patent/JPH05504937A/en
Priority to EP90905558A priority patent/EP0472531B1/en
Publication of FR2648047A2 publication Critical patent/FR2648047A2/en
Priority to OA60096A priority patent/OA09558A/en
Publication of FR2648047B2 publication Critical patent/FR2648047B2/en
Application granted granted Critical
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D311/00Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/60Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
    • C07D311/62Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2 with oxygen atoms directly attached in position 3, e.g. anthocyanidins

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention relates to a use of the polyphenolic derivatives according to Claim 9 of the main Patent Application No. 89/06,282. It comprises the use of these polyphenolic derivatives in pharmaceutical compositions against a virus chosen from the group consisting of AIDS, herpes, chickenpox, influenza A and ECHO 25 viruses. Use in the pharmaceutical industry.

Description

La présente invention concerne une application du produit
polyphénolique objet de la demande de brevet principal n" 89 06282.
The present invention relates to an application of the product
polyphenolic subject of main patent application no. 89 06282.

Cette demande revendique un produit polyphénolique caractérisé par le fait qu'il peut être obtenu par extraction à partir d'organes végétaux au moyen de solvant polaire volatil et par concentration de l'extrait. This application claims a polyphenolic product characterized in that it can be obtained by extraction from plant organs by means of volatile polar solvent and by concentration of the extract.

Il a également pour objet des compositions pharmaceutiques comportant ledit produit et l'utilisation dudit produit pour fabriquer des compositions pharmaceutiques anti-virales. It also relates to pharmaceutical compositions comprising said product and the use of said product to manufacture anti-viral pharmaceutical compositions.

Au cours de l'étude ultérieure au dépôt de cette demande de brevet, il a été montré que le produit polyphénolique décrit dans la demande de brevet principal présentait des propriétés anti-virales à la fois exceptionnelles et à large spectre. Ainsi, le présent certificat d'addition a pour objet de nouvelles utilisations dudit produit. During the study subsequent to the filing of this patent application, it was shown that the polyphenolic product described in the main patent application had both exceptional and broad spectrum anti-viral properties. Thus, the present certificate of addition relates to new uses of the said product.

Selon la revendication 9 de la demande de brevet principal, "l'utilisation du produit selon l'une des revendications I à 6 de la demande de brevet principal pour fabriquer des compositions pharmaceutiques anti-virales" donne de bons résultats, notamment pour les cas d'herpès. According to claim 9 of the main patent application, "the use of the product according to one of claims I to 6 of the main patent application to manufacture anti-viral pharmaceutical compositions" gives good results, especially for cases herpes.

Selon la présente invention, I'utilisation des produits selon l'une des revendications I à 6 pour fabriquer des compositions pharmaceutiques anti-virales donne des résultats particulièrement intéressants lorsqu'il s'agit de combattre des virus choisis dans le groupe constitué par le virus du syndrome immunodéficitaire acquis humain, de l'herpès de la varicelle-zona, de l'Influenza A et Echo 25. According to the present invention, the use of the products according to one of claims I to 6 for manufacturing anti-viral pharmaceutical compositions gives particularly advantageous results when it comes to combating viruses chosen from the group consisting of the virus. acquired human immunodeficiency syndrome, varicella-zoster herpes, Influenza A and Echo 25.

Il convient en outre d'indiquer que le produit selon les revendications I à 6 de la demande de brevet principal, présente une excellente activité virucide vis-à-vis du virus du syndrome immunodéficitaire acquis humain (HIV1). It should also be noted that the product according to claims I to 6 of the main patent application exhibits excellent virucidal activity vis-à-vis the human acquired immunodeficiency syndrome virus (HIV1).

Les exemples qui suivent illustrent cette activité anti-virale plus spécifique du produit selon la demande de brevet principal.  The following examples illustrate this more specific anti-viral activity of the product according to the main patent application.

Exemple I
Essai des proceanidols solubles dans l'eau de Cupressus sempervirens sur le virus du syndrome immunodéficitaire acquis humain (HIVI).
Example I
Test of water-soluble proceanidols of Cupressus sempervirens on the human acquired immunodeficiency syndrome virus (HIVI).

a) Effet antiviral
L'essai est réalisé sur des cellules H9 infectées par des dilutions décimales successives de HIVI pendant 90 minutes.
a) Antiviral effect
The test is carried out on H9 cells infected with successive decimal dilutions of HIVI for 90 minutes.

Après infection des cellules, celles-ci sont traitées par des concentrations décroissantes de procyanidols à des doses inférieures à la cytotoxicité constatée sur cette lignée cellulaire (150 pg/ml).  After infection of the cells, these are treated with decreasing concentrations of procyanidols at doses lower than the cytotoxicity observed on this cell line (150 pg / ml).

Après 10 jours de culture, les cellules sont centrifugées et les virus sont recherchés par un examen radio-immunologique (recherche de la protéine p 24) sur le surnageant. After 10 days of culture, the cells are centrifuged and the viruses are sought by radioimmunological examination (search for the protein p 24) on the supernatant.

Résultats
Les procyanidols solubles du cyprès obtenus selon l'exemple
I de la demande de brevet principal n" 89 06282, procurent une inhibition de l'expression virale de 97 % à la concentration de 50 pg/ml.
Results
The soluble procyanidols of cypress obtained according to the example
I of main patent application No. 89 06282, provide an inhibition of viral expression of 97% at a concentration of 50 pg / ml.

b) Effet virucide
La suspension virale (HIV1) est traitée pendant 30 minutes à 37"C par des concentrations décroissantes de procyanidols solubles du cyprès. Puis les cellules H9 sont infectées par des dilutions décimales successives de la suspension précédente.
b) Virucidal effect
The viral suspension (HIV1) is treated for 30 minutes at 37 ° C. with decreasing concentrations of soluble procyanidols of the cypress. Then the H9 cells are infected by successive decimal dilutions of the preceding suspension.

Résultats
Les procyanidols solubles du cyprès procurent une réduction du titre viral de 1,5 log (titre initial : 3.104) à la concentration de 50 pg/ml, et une réduction de 2,5 log à la concentration de 150 pg/ml.
Results
The soluble cypress procyanidols provide a reduction of the viral titer of 1.5 log (initial titer: 3.104) at the concentration of 50 pg / ml, and a reduction of 2.5 log at the concentration of 150 pg / ml.

Exemple 2
Essai des procyanidols solubles dans l'eau de Cupressus sempervirens sur le virus de l'herpès Simplex de type 11
Les essais antiviraux ont été réalisés sur le virus de l'herpès simplex type 11 implanté sur des fibroblastes de poumon embryonnaire humain.
Example 2
Test of water-soluble procyanidols of Cupressus sempervirens on herpes simplex virus type 11
The antiviral tests were carried out on the herpes simplex virus type 11 implanted on fibroblasts of human embryonic lung.

On a déterminé sur un lot de suspension virale correspondant à une dose infectante 50 (Dl 50 ) 2,5.104 virus par puit, l'efficacité antivirale des procyanidols solubles de Cupressus sempervirens, ctest-à-dire la quantité de produit par puit (c'est-à-dire dans 100 pI de milieu) qui provoque une diminution de moitié de la Du 50.  The antiviral efficacy of soluble Cupressus sempervirens procyanidols, i.e. the amount of product per well, was determined on a batch of viral suspension corresponding to an infectious dose 50 (LD 50) 2.5.104 viruses per well. (i.e. in 100 pI of medium) which causes the Du 50 to be halved.

La valeur trouvée est de 3,3 pg/100 ml. The value found is 3.3 pg / 100 ml.

Exemple 3
Essai des procyanidols solubles dans l'eau de Cupressus sempervirens sur le virus Varicelle-Zona
Les essais antiviraux ont été réalisés sur le virus de la varicelle et du zona implanté sur des fibroblastes. de poumon embryonnaire humain.
Example 3
Test of water-soluble procyanidols of Cupressus sempervirens on Varicella zoster virus
The antiviral tests were carried out on the chickenpox and shingles virus implanted on fibroblasts. of human embryonic lung.

On a déterminé un lot de suspension virale correspondant à une dose infectante 50 (DIS0) 5.103 virus par puit, I'efficacité anti-virale des procyanidols solubles de Cupressus sempervirens, c'est-à-dire la quantité de produit par puit (c'est-à-dire 100 pI de milieu) qui provoque une diminution de moitié de la D150. A batch of viral suspension corresponding to an infectious dose of 50 (DIS0) 5,103 viruses per well was determined, the anti-viral efficacy of the soluble procyanidols from Cupressus sempervirens, that is to say the quantity of product per well (c (i.e. 100 pI of medium) which causes the D150 to be halved.

La valeur trouvée est de 6 pg/100 ml.  The value found is 6 pg / 100 ml.

Exemple 4
Essai des procyanidols solubles dans l'eau de Cupressus sempervirens sur le virus Influenza A
Les essais antiviraux ont été réalisés sur le virus Influenza
A implanté sur des cellules d'adénocarinome de colon humain.
Example 4
Influenza A virus test of water-soluble procyanidols of Cupressus sempervirens
Antiviral tests have been carried out on the Influenza virus
Implanted on human colon adenocarinoma cells.

On a déterminé sur un lot de suspension virale correspondant à une dose infectante 50 (DIS0) 7.103 virus par puit, I'efficacité antivirale des procyanidols solubles de Cupressus sempervirens, c'est-à-dire la quantité de produit par puit (c'est-à-dire dans 100 PI de milieu) qui provoque une diminution de moitié de la DISE. The antiviral efficacy of the soluble Cupressus sempervirens procyanidols, that is to say the quantity of product per well, was determined on a batch of viral suspension corresponding to an infectious dose of 50 (DIS0) 7,103 viruses per well. i.e. in 100 PI of medium) which causes a halving of the DISE.

La valeur trouvée est de 12 pu/100 ml. The value found is 12 pu / 100 ml.

Exemple 5
Essai des procyanidols solubles dans l'eau de Cupressus sempervirens sur le virus ECHO 25
Les essais antiviraux ont été réalisés sur le virus ECHO 25 implanté sur des fibroblastes de poumon embryonnaire humain
On a déterminé sur un lot de suspension virale correspondant à une dose infectante 50 (D150) 104 virus par puit, I'efficacité antivirale des procyanidols solubles de Cupressus sempervirens, c'est-à-dire la quantité de produit par puit (c'est-à-dire dans 100 pI de milieu) qui provoque une diminution de moitié de la DISO.
Example 5
Test of water-soluble procyanidols of Cupressus sempervirens on the ECHO 25 virus
The antiviral tests were carried out on the ECHO 25 virus implanted on human embryonic lung fibroblasts
The antiviral efficacy of soluble Cupressus sempervirens procyanidols, i.e. the quantity of product per well, was determined on a batch of viral suspension corresponding to an infectious dose of 50 (D150) 104 viruses per well. i.e. in 100 pI of medium) which causes a halving of the DISO.

La valeur trouvée est de 31 pu/ 100 ml.  The value found is 31 pu / 100 ml.

Claims (2)

REVENDICATIONS 1. Utilisation selon la revendication 9 de la demande de brevet principal nO 89 06282, caractérisée par le fait que lesdites compositions pharmaceutiques antivirales sont des compositions pharmaceutiques contre un virus choisi dans le groupe constitué par les virus du 1. Use according to claim 9 of main patent application No. 89 06282, characterized in that said antiviral pharmaceutical compositions are pharmaceutical compositions against a virus chosen from the group consisting of viruses SIDA, de l'herpès, de la varicelle, de l'lnfluenza A et ECHO 25.AIDS, herpes, chickenpox, influenza A and ECHO 25. 2. Utilisation selon la revendication I, caractérisée par le fait que ladite composition pharmaceutique antivirale est une composition virucide.  2. Use according to claim I, characterized in that said antiviral pharmaceutical composition is a virucidal composition.
FR8907654A 1989-05-12 1989-06-09 POLYPHENOLIC PRODUCT WITH ANTIVIRAL ACTIVITY Expired - Lifetime FR2648047B2 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
FR8907654A FR2648047B2 (en) 1989-05-12 1989-06-09 POLYPHENOLIC PRODUCT WITH ANTIVIRAL ACTIVITY
ES90905558T ES2078339T3 (en) 1989-05-12 1990-03-23 COMPOSITIONS BASED ON PROANTOCIANIDOLES; YOUR PHARMACOLOGICAL APPLICATION.
JP2505329A JPH05504937A (en) 1989-05-12 1990-03-23 Compositions based on proanthocyanidol. Its pharmacological application
DK90905558.4T DK0472531T3 (en) 1989-05-12 1990-03-23 Composition based on proanthocyanidols and their pharmacological use
DE69021725T DE69021725T2 (en) 1989-05-12 1990-03-23 COMPOSITION BASED ON PROANTHOCYANIDOLS AND THEIR PHARMACEUTICAL USE.
AT90905558T ATE126439T1 (en) 1989-05-12 1990-03-23 COMPOSITION BASED ON PROANTHOCYANIDOLS AND THEIR PHARMACEUTICAL USE.
PCT/FR1990/000200 WO1990013304A1 (en) 1989-05-12 1990-03-23 Proanthocyanidol-based composition and its pharmacological application
AU54000/90A AU648754B2 (en) 1989-05-12 1990-03-23 Proanthocyanidol-based composition and its pharmacological application
CA002057023A CA2057023A1 (en) 1989-05-12 1990-03-23 Proanthocyanidol composition and pharmacological use thereof
EP90905558A EP0472531B1 (en) 1989-05-12 1990-03-23 Proanthocyanidol-based composition and its pharmacological application
OA60096A OA09558A (en) 1989-05-12 1991-11-12 Compositions based on proanthocyanidols their pharmacological application

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR8906282A FR2646852B1 (en) 1989-05-12 1989-05-12 POLYPHENOLIC PRODUCT WITH ANTIVIRAL ACTIVITY
FR8907654A FR2648047B2 (en) 1989-05-12 1989-06-09 POLYPHENOLIC PRODUCT WITH ANTIVIRAL ACTIVITY

Publications (2)

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FR2648047A2 true FR2648047A2 (en) 1990-12-14
FR2648047B2 FR2648047B2 (en) 1994-09-02

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FR8907654A Expired - Lifetime FR2648047B2 (en) 1989-05-12 1989-06-09 POLYPHENOLIC PRODUCT WITH ANTIVIRAL ACTIVITY

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0025649B1 (en) * 1979-08-23 1983-10-26 Orewa Inc. Pharmaceutical composition containing sanguinaria and galangal suitable for treatment of periodentitis and tumours

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0025649B1 (en) * 1979-08-23 1983-10-26 Orewa Inc. Pharmaceutical composition containing sanguinaria and galangal suitable for treatment of periodentitis and tumours

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 100, no. 16, 16 avril 1984, page 355, abrégé no. 126823x, Columbus, Ohio, US; S.H. MISRA et al.: "Pharmaceutical studies on starches of some zingiberaceous rhizomes", & INDIAN J. PHARM. SCI. 1983, 45(5), 216-20 *

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