EP1663271A1 - Utilisation d'extraits de gentiana lutea comme agent antimicrobien - Google Patents

Utilisation d'extraits de gentiana lutea comme agent antimicrobien

Info

Publication number
EP1663271A1
EP1663271A1 EP04765012A EP04765012A EP1663271A1 EP 1663271 A1 EP1663271 A1 EP 1663271A1 EP 04765012 A EP04765012 A EP 04765012A EP 04765012 A EP04765012 A EP 04765012A EP 1663271 A1 EP1663271 A1 EP 1663271A1
Authority
EP
European Patent Office
Prior art keywords
extract
use according
infections
gentiana lutea
treatment
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.)
Withdrawn
Application number
EP04765012A
Other languages
German (de)
English (en)
Inventor
Pontus Stierna
Michael A. Popp
Chaim Ismail
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bionorica SE
Original Assignee
Bionorica SE
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Bionorica SE filed Critical Bionorica SE
Publication of EP1663271A1 publication Critical patent/EP1663271A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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)
    • A61K36/51—Gentianaceae (Gentian family)
    • A61K36/515—Gentiana
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to the use of an extract from Gentiana lutea (yellow gentian) for the treatment of bacterial infections as well as an antimicrobial agent as claimed in claim 7.
  • Gentiana lutea is part of the applicant's fixed drug combination ® SINUPRET.
  • the herbal drug combination has been used in inflammation of the upper and lower respiratory tract for decades. The effectiveness of the drug has been proven in several controlled clinical trials.
  • Other active pharmaceutical ingredients of the above-mentioned fixed drug combination are Flores Primulae cum Calycibus, Herba Rumicis, Flores Sambuci and Herba Verbenae.
  • antibiotics In addition, it is generally known to treat infections in humans and animals using synthetic or semi-synthetic antibiotics.
  • the group of ⁇ -lactam antibiotics is known, which also includes penicillin and ampicillin. Due to their chemical nature and synthesis-related enantiomer mixtures, antibiotics of this type - in addition to increasing patient resistance to the application of chemical products - often have undesirable side effects.
  • the present invention relates in particular to the use of an extract of plant material from Gentiana lutea (yellow gentian) for the manufacture of a medicament for the treatment of bacterial infections, which are selected from the group consisting of: infections with: Gram-positive bacteria, in particular clostridia, streptococci, preferably Streptococcus pneumoniae; and Staphylococcus aureus, preferably methicillin-resistant Staphylococcus aureus, particularly preferably Staphylococcus aureus NCTC 11940.
  • the extract from Gentiana lutea can be used particularly advantageously for the treatment of infections of the upper and lower respiratory tract such as rhinosinusitis, in particular maxillary sinus and / or frontal sinusitis, and bronchitis.
  • An advantageous use of the present invention is based on the use of the extract from Gentiana lutea for the treatment of bacterial superinfections of primary diseases caused by viruses.
  • the present invention further relates to an antimicrobial agent which contains an extract of material from Gentiana lutea (yellow gentian).
  • the agent, in particular medicament is extracted by extracting plant material, in particular roots, using organic solvents, in particular polar solvents, preferably alcohols, particularly preferably ethanol, in particular mixtures of ethanol with water, preferably 50% by volume of ethanol; or produced using supercritical CO2, the extract being obtained in a temperature range from 31 ° C to 90 ° C and a pressure range from 75 to 500 bar and the separation in a temperature range from 10 ° C to 50 ° C and a pressure range from 1 bar up to 74 bar.
  • organic solvents in particular polar solvents, preferably alcohols, particularly preferably ethanol, in particular mixtures of ethanol with water, preferably 50% by volume of ethanol; or produced using supercritical CO2, the extract being obtained in a temperature range from 31 ° C to 90 ° C and a pressure range from 75 to 500 bar and the separation in a temperature range from 10 ° C to 50 ° C and a pressure range from 1 bar up to 74 bar.
  • the agent can of course be produced in the usual galenical formulations, in particular coated tablets, tablets, drops of syrup, sprays, in particular nasal sprays, ointments, creams, but also as a preparation for injection.
  • the antibiotic agent based on Gentiana lutea has at least the antibiotic effectiveness of ampicillin when plating mucosal samples on blood agar plates against Streptococcus pneumoniae.
  • the extract from Gentiana lutea can be used, for example, orally in a dose of approximately 100 mg / kg to 1000 mg mg / kg, in particular approximately 200 mg / kg to 500 mg / kg, preferably approximately 300 mg / kg extract.
  • the antimicrobial effect of the preparation according to the invention from the root of Gentiana lutea was demonstrated in a study in whole animals.
  • the model used is the standard model according to Naclerio [Bomer et al .: Archives of Otolaryngology - Head and Neck Surgery, 1998].
  • 1 shows a bar graph which shows the bacterial growth after an 8-day application of an extract from Gentiana lutea in comparison with the anti-inflammatory dexamethasone and the antibiotic ampicillin against an untreated control;
  • FIG. 2 shows a bar graph which shows the loss of cilia of the nose and sinus mucosa after 8 days of application of dexamethasone and ampicillin against an untreated control;
  • FIG. 3 shows a bar graph which shows the loss of cilia in the nose and sinus mucosa after 8 days of application of an extract from Gentiana lutea against an untreated control;
  • FIG. 4 shows a bar graph which shows the measured secretion of the nasal and sinus mucosa after 8 days of application of dexamethasone and ampicillin against an untreated control;
  • 5 is a bar graph which shows the measured secretion of the nose and sinus mucosa after 8 days of application of an extract from Gentiana lutea against an untreated control
  • 6 is a microphotograph of a histological section (hematoxylin-eosin staining) of the nose and sinuses in black and white reproduction of animals treated with ampicillin;
  • FIG. 7 shows a microphotograph of a histological section (Alcian blue Pas staining) of the nose and sinuses in black and white reproduction of animals treated with dexamethasone;
  • FIG. 8 shows a photomicrograph of a histological section (hematoxylin-eosin staining) of the nose and sinuses in black and white reproduction of animals which were treated according to the invention with an extract from Gentiana lutea;
  • FIG. 9 is a photomicrograph of a histological section (hematoxylin-eosin staining) of the nose and sinuses in black and white reproduction of animals that were sham-treated for control.
  • mice with streptococcus pneumoniae, serotype 3 are locally infected by application of the pathogen into the nose. Exposure to the bacteria causes bacterial inflammation of the nose and sinuses in the animals - rhinosinusitis.
  • mice were infected as described above.
  • the mice were randomly assigned to different treatment groups.
  • the groups consisted of at least 50 experimental animals.
  • the mice were either sham-treated, with an extract from the root of Gentiana lutea, an antibiotic (ampicillin) or dexamethasone.
  • the extract from the root of Gentiana radix was produced by means of extraction (ethanol concentration extracting agent 50% V ⁇ , room temperature, extraction time: 7 hours) and drying (drying time 20 hours, maximum product temperature 45C).
  • the extract from the roots of Gentianae lutea was taken orally, the test substance was dissolved in a sugar solution.
  • the concentration administered was 300 mg of extract per kg of animal body weight per day.
  • the sham-treated animals only took the sugar solution without test substance.
  • the application of the antibiotic 300 mg per kg of animal body weight per day was also administered orally.
  • Dexamethasone (1 ⁇ g per kg animal body weight per day) was administered parenterally.
  • the treatment started in parallel with the induction of bacterial rhinosinusitis.
  • the duration of the sham treatment, the treatment with the extract from the root of Gentiana lutea and the treatment with the antibiotic were carried out for 4 and 8 days, respectively.
  • Treatment with dexamethasone was given only once on the day of infection.
  • Half of the animals were killed 4 days after induction of the infection, the other half were killed 8 days after the induction of infection.
  • Samples of the left and right paranasal sinuses were removed with a sterile swab and spread directly onto blood agar plates and incubated under aerobic as well as anaerobic conditions at 37 C for 48 hours.
  • the bacteria isolated were characterized using a Gram test and morphology.
  • the oxidase test was carried out and the AP1 20 NE test (bioMerieux, France) was used for identification.
  • the nose and paranasal sinuses were fixed in 4% paraformaldehyde, decalcified and embedded in paraffin.
  • the entire complex was serially cut into 5 micron layers.
  • the staining was carried out using two different staining methods, hematoxylin-eosin, Alcian blue-Pas.
  • Inflammation of the upper respiratory tract (especially rhinosinusitis) and the lower respiratory tract (especially bronchitis) is primarily caused by viruses.
  • superinfection with bacterial pathogens is typical of the diseases mentioned.
  • the bacterium Streptococcus pneumoniae used in this model is one of the typical germs that cause a bacterial superinfection on the respiratory tract.
  • Antibiotics especially the ampicillin used in this model, are among the therapeutic options in the treatment of infections of the upper and lower respiratory tract.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Oncology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l'utilisation d'un extrait de Gentiana lutea (gentiane jaune) comme médicament pour traiter des infections bactériennes. On a découvert que cet extrait présente un effet antimicrobien correspondant à celui de l'ampicilline. Ce nouveau médicament peut être produit dans toutes les formulations galéniques usuelles et il est tout particulièrement approprié pour traiter des infections des voies aériennes supérieures et inférieures, telles que les rhinosinusites et les bronchites.
EP04765012A 2003-09-09 2004-09-09 Utilisation d'extraits de gentiana lutea comme agent antimicrobien Withdrawn EP1663271A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10341579A DE10341579A1 (de) 2003-09-09 2003-09-09 Verwendung von Extrakten aus Gentiana lutea als antimikrobiell wirkendes Mittel
PCT/EP2004/010079 WO2005025585A1 (fr) 2003-09-09 2004-09-09 Utilisation d'extraits de gentiana lutea comme agent antimicrobien

Publications (1)

Publication Number Publication Date
EP1663271A1 true EP1663271A1 (fr) 2006-06-07

Family

ID=34258523

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04765012A Withdrawn EP1663271A1 (fr) 2003-09-09 2004-09-09 Utilisation d'extraits de gentiana lutea comme agent antimicrobien

Country Status (7)

Country Link
US (1) US20070184125A1 (fr)
EP (1) EP1663271A1 (fr)
CN (1) CN1849130A (fr)
BR (1) BRPI0414223A (fr)
DE (1) DE10341579A1 (fr)
RU (1) RU2006105260A (fr)
WO (1) WO2005025585A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005053926B3 (de) * 2005-11-11 2007-06-28 Bionorica Ag Verwendung eines antibakteriellen Mittels aus einer Mischung aus Pflanzendrogen oder Extrakten daraus
DE102007052223A1 (de) 2007-10-31 2009-05-14 Bionorica Ag Hydrolysate aus Pflanzenextrakten sowie diese enthaltendes antibakterielles Mittel
AU2012298534B2 (en) * 2011-08-19 2016-06-30 Bionorica Se Method for producing dry extracts

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6355684B1 (en) * 1990-10-11 2002-03-12 Meryl J. Squires Antimicrobial treatment for herpes simplex virus and other infectious diseases
US5837254A (en) * 1996-11-14 1998-11-17 Chen; Yu Method of treating candida and cryptococcus fungal infections by administering gentian
AU771575B2 (en) * 1998-08-06 2004-03-25 Rutgers, The State University Of New Jersey A method of identifying and recovering products exuded from a plant
FR2794600B1 (fr) 1999-06-01 2001-08-17 Thomson Multimedia Sa Systeme de tatouage de donnees utilisant de nouvelles methodes d'insertion et de detection de tatouage
US20020031559A1 (en) * 2000-03-08 2002-03-14 Liang Kin C. Herbal suppositories
CN1175880C (zh) * 2002-08-27 2004-11-17 王汝芝 一种治疗鼻窦炎的药物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005025585A1 *

Also Published As

Publication number Publication date
DE10341579A1 (de) 2005-04-07
RU2006105260A (ru) 2007-10-20
CN1849130A (zh) 2006-10-18
US20070184125A1 (en) 2007-08-09
WO2005025585A1 (fr) 2005-03-24
BRPI0414223A (pt) 2006-10-31

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