FR2513518A1 - Polysaccharide prodn. from Gnida kraussiana - for treatment of respiratory infections, asthma, psoriasis, and certain chronic lymphoid leukaemia(s) - Google Patents

Polysaccharide prodn. from Gnida kraussiana - for treatment of respiratory infections, asthma, psoriasis, and certain chronic lymphoid leukaemia(s) Download PDF

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FR2513518A1
FR2513518A1 FR8118508A FR8118508A FR2513518A1 FR 2513518 A1 FR2513518 A1 FR 2513518A1 FR 8118508 A FR8118508 A FR 8118508A FR 8118508 A FR8118508 A FR 8118508A FR 2513518 A1 FR2513518 A1 FR 2513518A1
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treatment
polysaccharide
kraussiana
psoriasis
asthma
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)

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  • Natural Medicines & Medicinal Plants (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
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  • Materials Engineering (AREA)
  • Alternative & Traditional Medicine (AREA)
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Abstract

Polysaccharide (I) is extracted from Gnidia kraussiana, a thymelaeaceous plant of the African savanna, by treating the crushed tubers with hot chloroform and methanol to eliminate toxic components, and then with hydrochloric acid. The acid extract is then dialysed and may be dried. Polysaccharide (I) contains arabinose, xylose, rhamnose, fructose, galactose and glucose in the ratio 2:51:6:3:21:15. It is 55% soluble in water, and 0.15% soluble in chloroform. The treatment with chloroform is effected at 40-50 deg.C, and this is followed by methanol extrn. using a Soxhlet. Rapid treatment with HCl follows, the extract being dialysed at pH 5. Used for treatment of all disorders connected with hypogamma -globulinaemia, such as chronic respiratory tract infetions, all allergies with hypogammaglobulinaenia, such as asthma, eczema and food allergies, treatment of certain delayed hypersensitivity disorders such as psoriasis, and treatment of certain chronic lymphoid leukaemias.

Description

Les tubercules de Gnidia kraussiana, Thyméléacée de la savane africaine, étaient utilises avec succès par la pharmacopée traditionnelle africaine contre la forme lépromateuse de la lèpre, malgré sa toxicité (vomissements, diarrhées sanglantes). The tubers of Gnidia kraussiana, Thymeleea of the African savannah, were successfully used by the traditional African pharmacopoeia against the lepromatous form of leprosy, despite its toxicity (vomiting, bloody diarrhea).

Les recherches phytochimiques et pharmacodynamiques ont per mis
10) d'éliminer les esters de diterpénoides à fonctions époxides et étheroxydes entre phénols responsables de la forte toxité de la plante à l'état naturel.Phytochemical and pharmacodynamic research has enabled
10) to eliminate the diterpenoid esters with epoxy and etheroxide functions between phenols responsible for the high toxicity of the plant in its natural state.

20) d'isoler sous forme cristallisée un hétéroside triterpénique pharmacologiquement actif (cf. brevet spécial de médi- cament, dépôt n 81.14.903). 20) to isolate in crystallized form a pharmacologically active triterpene heteroside (cf. special drug patent, deposit no. 81.14.903).

30) d'identifier et de préciser les usages thérapeutiques d'un polyssaccharide possédant des propriétés immunomodificatrices.  30) to identify and specify the therapeutic uses of a polyssaccharide having immunomodifying properties.

Ce dernier produit fait l'objet de la présente demande de-brevet spécial de médicaments. This latter product is the subject of this special patent application for medicaments.

2 - PREPARATION
Les tubercules broyés sont détoxiqués au chloroforme à l'aide d'extracteur atomiseur : température du solvant hO-50 C. 2 - PREPARATION
The ground tubers are detoxified with chloroform using an atomizing extractor: solvent temperature hO-50 C.

La poudre de racines est alors séchée puis lavée à l'eau bouillante durant 90 mn. Après essorage, séchage, elle est extraite au mé- thanol chaud durant 36 heures dans un appareil de Soxhlet. Après éli- mination du solvant restant dans la plante, les racines subissent un traitement rapide à l'acide chlorhydrique concentré puis dilué. L'extrait chlorhydrique est immédiatement mis en dialyse jusqu'à ce que le pH du contenu des tubes à dialyse soit de 6,5.  The root powder is then dried and then washed with boiling water for 90 minutes. After spinning, drying, it is extracted with hot methanol for 36 hours in a Soxhlet apparatus. After removal of the solvent remaining in the plant, the roots are quickly treated with concentrated hydrochloric acid and then diluted. The hydrochloric extract is immediately put on dialysis until the pH of the contents of the dialysis tubes is 6.5.

On obtient ainsi une solution contenant environ 3%e d'extrait 'i' végétal, qui est desséché. ^
Le produit de cette dessication, riche en polysaccharide, est une poudre grisatre propre à l'usage pharmaceutique, après conditionnement en gélules par exemple.This gives a solution containing about 3% e of plant extract 'i', which is dried. ^
The product of this desiccation, rich in polysaccharide, is a grayish powder suitable for pharmaceutical use, after packaging in capsules for example.

Une préparation purifiée du polysaccharide peut être obtenue en extrayant toutes les substances solubles dans l'eau bouillante avant le traitement chlorhydrique des tubercules. A purified preparation of the polysaccharide can be obtained by extracting all the substances soluble in boiling water before the hydrochloric treatment of the tubers.

3 - DESCRIPTION
L'extrait végétal conditionnable en gélules présente les caractores physiques suivants (précision t 5%)
Solubilité dans l'eau 55%
Solubilité dans le CHCl3 0,15%
La fraction chloroformo-soluble est insoluble dans l'eau, les alcools et les divers solvants organiques essayés ; cette fraction ne contient donc pas d'esters de diterpénoides toxiques ; ceux-ci sont en effet solubles dans les alcools
La fraction soluble dans l'eau est constituée principalement par le polysaccharide.3 - DESCRIPTION
The plant extract which can be packaged in capsules has the following physical characteristics (accuracy t 5%)
Solubility in water 55%
Solubility in CHCl3 0.15%
The chloroform-soluble fraction is insoluble in water, alcohols and the various organic solvents tested; this fraction therefore does not contain toxic diterpenoid esters; these are indeed soluble in alcohols
The water-soluble fraction consists mainly of the polysaccharide.

Identification du polysaccharide. Identification of the polysaccharide.

- Substance non azote selon une analyse qualitative partielle sur le produit purifié ; cette analyse a- été effectue par Monsieur le Professeur MILA, Ecole de Chimie de Toulouse. - Non-nitrogenous substance according to a partial qualitative analysis on the purified product; this analysis was carried out by Professor MILA, Toulouse School of Chemistry.

- L'hydrolyse acide (HCl.2N') libère des sucres réducteurs; après élimination du H.U par concentration sous vide à une température inférieure à 400C, l'hydrolysat est chromatographié sur papier
Whatman n 1 dans différents solvants afin de séparer les diverses catégories d'oses. La révélation des chromatogrammes avec le réactif à la paraanisidine phosphate et celui à l'acide phtalique montre la présence de 6 oses : arabinose, xylose, rhamnose, fructose, galactose, glucose.
La chromatographie en phase gazeuse permet de déterminer les proportions suivantes de ces oses 2;51;6;3;21;15.- Acid hydrolysis (HCl.2N ') releases reducing sugars; after removal of the HU by concentration under vacuum at a temperature below 400C, the hydrolyzate is chromatographed on paper
Whatman # 1 in different solvents to separate the various categories of oses. The revelation of the chromatograms with the reagent with paraanisidine phosphate and that with phthalic acid shows the presence of 6 oses: arabinose, xylose, rhamnose, fructose, galactose, glucose.
Gas chromatography makes it possible to determine the following proportions of these oses 2; 51; 6; 3; 21; 15.

IV - PHARMACODYNAMIQUE
1 - Effet sur la formule sanguine et les protéines sériques des lapins
L'injection intraveineuse à un lot de lapins de 2 mg/kg de pro duit purifié, détermine de façon constante chez chacun des sujets:
a) 10 jours après l'injection
- Une diminution de 30 à 50% du nombre absolu des lymphocytes circulants, les autres lignées ne sont pas significativement modifixées.IV - PHARMACODYNAMICS
1 - Effect on the blood formula and serum proteins of rabbits
Intravenous injection into a batch of rabbits of 2 mg / kg of purified product, consistently determines in each of the subjects:
a) 10 days after the injection
- A decrease of 30 to 50% in the absolute number of circulating lymphocytes, the other lines are not significantly modified.

- Une augmentation des gammaglobulines de 40 à 100%
b) 20 jours après l'injection, les lymphocytes sont revenus à leur taux normal ; les gammaglobulines restent élevées, quelques plasmocytes apparaissent dans le sang.- An increase in gamma globulin from 40 to 100%
b) 20 days after the injection, the lymphocytes returned to their normal rate; the gamma globulins remain high, some plasma cells appear in the blood.

Des phénomènes du même ordre sont obtenus avec 3 prises due 2mg/kg per os, 3 jours consécutifs. Similar phenomena are obtained with 3 doses of 2 mg / kg per os, 3 consecutive days.

2 - Modification du poids de la rate des souris
La même dose de 2mg/kg est injectée à 10 souris par voie veineuse.2 - Modification of the weight of the spleen of mice
The same dose of 2 mg / kg is injected into 10 mice by venous route.

7 jours après ces 10 souris sont sacrifiées, ainsi qu'un lot témoin de 10 souris. On calcule le rapport : poids de la rate
poids de l'animal
-Rapport moyen du lot traité : 0,0028
Rapport moyen du lot témoin : 0,0051
Ces deux tests prouvent l'action antilymphocytaire du produit.7 days after these 10 mice are sacrificed, as well as a control batch of 10 mice. We calculate the ratio: weight of the spleen
animal weight
-Average report of the treated batch: 0.0028
Average control lot ratio: 0.0051
These two tests prove the antilymphocytic action of the product.

L'augmentation des gammaglobulines est très probablement due a l'inhi bition par la drogue du système répresseur de l'immunité sérique, sys tème répresseur supporté par les lymphocytes T, responsables de l'im munit cellulaire ; la lignée plasmocytaire ainsi libérée augmente sa production d'immuglobulines.The increase in gamma globulin is very probably due to the drug inhibition of the repressor system of serum immunity, repressor system supported by T lymphocytes, responsible for cellular immunity; the plasma cell line thus released increases its production of immunoglobulins.

L'extrait végétal est donc un stimulant spécifique de l'immunité séri
C'est certainement cette propriété d'augmenter les gammaglobu liners qui rend compte de l'efficacité du produit dans de nombreuses allergies et affections hypoimmunes respiratoires. Semblable augmentation des gammaglobulines est en effet obseve'e chez l'homme.The plant extract is therefore a specific stimulant of serious immunity
It is certainly this property of increasing the gammaglobu liners which accounts for the effectiveness of the product in many allergies and respiratory hypoimmune conditions. Similar increase in gamma globulin is indeed observed in humans.

V - TOXICOLOGIE
Les premiers essais effectués au iaboratoire de pharmacologie et toxicologie fondamentales du C.N.R.S. de TOULOUSE, ont montre l'ail sence apparente de mutagénicité. V - TOXICOLOGY
The first tests carried out at the laboratory of fundamental pharmacology and toxicology of the CNRS of TOULOUSE, showed the apparent resistance to mutagenicity.

On n'a pas observe de toxicite chez les souris pour une dose intrapéritonéale de 8Omg/kg.  No toxicity was observed in mice for an intraperitoneal dose of 80 mg / kg.

VI - USAGES CLINIQUES
Ces propriétés sont utilisables
10) Dans toutes les affections liées à une hypogammaglobulinémie infections chroniques de l'arbre respiratoire ou de la sphère O.R.L.VI - CLINICAL USES
These properties can be used
10) In all conditions linked to hypogammaglobulinemia chronic infections of the respiratory tree or the ENT sphere

20) Dans les allergies avec hypogammaglobulinémie : asthmes, eczémas, spécialement ceux des nourrissons, aphtose.s rebelles. 20) In allergies with hypogammaglobulinemia: asthma, eczema, especially those of infants, rebellious aphthosis.

30) Dans certaines affections liées à l'hypersensibilité retardE comme le psoriasis. 30) In certain conditions linked to delayed hypersensitivity such as psoriasis.

40) Dans certaines leucémies lymphoides chroniques, l'effet est particulier constant sur lthypoprotéinémie lide t la lymphomatose intestinale des leucémies lymphoides chroniques et des lymphosarcome
VII - PRESENTATION GALENIQUE - POSOLOGIE
L'extrait végétal ci-dessus décrit peut être mis en gélules.40) In certain chronic lymphocytic leukemias, the effect is particular constant on the low proteinoproteinemia and the intestinal lymphomatosis of chronic lymphocytic leukemias and lymphosarcoma
VII - GALENIC PRESENTATION - DOSAGE
The plant extract described above can be put in capsules.

A la dose de 60 mg par gélule, on administre 4 à 6 gdlules par jour. Les résultats cliniques sont obtenus après 5 à 10 jours pour les asthmes, les bronchites chroniques, les aphtoses, et après 20 à 40 jours pour les psoriasis et les leucémies lymptO;des chroniques.  At a dose of 60 mg per capsule, 4 to 6 capsules are administered per day. Clinical results are obtained after 5 to 10 days for asthma, chronic bronchitis, aphthoses, and after 20 to 40 days for psoriasis and leukemia lymptO; chronic.

Claims (2)

EEVENDICATIONSEVENTS 1) Extraction d'un polysaccharide du Gnidia kraussiana par traitement chlorhydrique des tubercules broyés, préalablement débarrassés des substances solubles à chaud dans le chloroforme, le méthanol et de la majeure partie de leurs constituants hydrosolubles ; l'élimination du HCl se faisant par dialyse. 1) Extraction of a polysaccharide from Gnidia kraussiana by hydrochloric treatment of the crushed tubers, previously freed from hot-soluble substances in chloroform, methanol and most of their water-soluble constituents; elimination of HCl by dialysis. 2) Utilisation de l'extrait végétal obtenu selon le procédé décrit dans la revendication 1, comme mddicament.  2) Use of the plant extract obtained according to the process described in claim 1, as a drug.
FR8118508A 1981-09-29 1981-09-29 Polysaccharide prodn. from Gnida kraussiana - for treatment of respiratory infections, asthma, psoriasis, and certain chronic lymphoid leukaemia(s) Granted FR2513518A1 (en)

Priority Applications (1)

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FR8118508A FR2513518A1 (en) 1981-09-29 1981-09-29 Polysaccharide prodn. from Gnida kraussiana - for treatment of respiratory infections, asthma, psoriasis, and certain chronic lymphoid leukaemia(s)

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FR8118508A FR2513518A1 (en) 1981-09-29 1981-09-29 Polysaccharide prodn. from Gnida kraussiana - for treatment of respiratory infections, asthma, psoriasis, and certain chronic lymphoid leukaemia(s)

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FR2513518A1 true FR2513518A1 (en) 1983-04-01
FR2513518B1 FR2513518B1 (en) 1984-02-17

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4677198A (en) * 1983-11-22 1987-06-30 Gist-Brocades N.V. Process for the preparation of oligosaccharides-containing products from biomass
FR2597752A1 (en) * 1986-04-24 1987-10-30 Tubery Pierre Synergistic effect between senegenin and the polysaccharide extracted from Gnidia kraussiana in the treatment of certain allergies
EP0304347A2 (en) * 1987-07-10 1989-02-22 Guyomarc'h Nutrition Animale Polysaccharides extracted from plants and useful as medicines and food additives
EP2551283A1 (en) * 2010-03-24 2013-01-30 Morishita Jintan Co., Ltd. Anti-allergic agent

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2871235A (en) * 1952-08-29 1959-01-27 Jilovice Vladimir Jan Hlous De Process for obtaining polysaccharide material from plants of the genus cecropia
FR7333M (en) * 1967-12-08 1969-10-13

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2871235A (en) * 1952-08-29 1959-01-27 Jilovice Vladimir Jan Hlous De Process for obtaining polysaccharide material from plants of the genus cecropia
FR7333M (en) * 1967-12-08 1969-10-13

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CA1975 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4677198A (en) * 1983-11-22 1987-06-30 Gist-Brocades N.V. Process for the preparation of oligosaccharides-containing products from biomass
FR2597752A1 (en) * 1986-04-24 1987-10-30 Tubery Pierre Synergistic effect between senegenin and the polysaccharide extracted from Gnidia kraussiana in the treatment of certain allergies
EP0304347A2 (en) * 1987-07-10 1989-02-22 Guyomarc'h Nutrition Animale Polysaccharides extracted from plants and useful as medicines and food additives
EP0304347A3 (en) * 1987-07-10 1989-03-08 Etablissements Guyomarc'h S.A. Polysaccharides extracted from plants and useful as medicines and food additives
EP2551283A1 (en) * 2010-03-24 2013-01-30 Morishita Jintan Co., Ltd. Anti-allergic agent
US20140154218A1 (en) * 2010-03-24 2014-06-05 Morishita Jintan Co., Ltd. Anti-allergic agent
EP2551283A4 (en) * 2010-03-24 2015-04-22 Morishita Jintan Co Anti-allergic agent

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