WORLDWIDE PHARMACEUTICAL FIELD - unipd.it · PDF fileYear of Isolation. 1806. 1817. 1832....
Transcript of WORLDWIDE PHARMACEUTICAL FIELD - unipd.it · PDF fileYear of Isolation. 1806. 1817. 1832....
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WORLDWIDE PHARMACEUTICAL FIELD
WESTERN COUNTRIES
DEVELOPING COUNTRIES
PERCENTAGE OF DRUGS OF BOTANICAL ORIGIN
20
80Data from WHO (2002)
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PlantPapaver somniferum L.
Strychnos nux - vomica L.Cephaelis ipecacuanha (Brot.) TussacCinchona ledgeriana Bern. Moens ex Trimen
Coffea arabica L.Colchicum autumnale L.Filipendula ulmaria (L.) Maxim.Atropa belladonna L.Theobroma cacao L.Erythroxylum coca Lam.Physostigma venenosum Bal.Pilocarpus jaborandi HolmesDatura metel L.Hyoscyamus niger L.Ephedra sinica Stapf.Digitalis purpurea L.Rauwolfia serpentina L.
Chondrodendron tomentosum Ruitz et PavonCatharantus roseus (L.) G. Don
Ammi visnaga (L.) Lam.Silybum marianum (L.) Gartn.Coleus forskohlii Brig.Taxus baccata L.Camptotheca acuminata L.
AgentMorphineNoscapineCodeinePapaverineStrychnineEmetineQuinineQuinidineCaffeineColchicineSalicinAtropineTheobromineCocainePhysostigminePilocarpineScopolamineHyoscyamineL-EphedrineDigoxinAjmalineReserpineRescinnamineTubocurarineVinblastineVincristineVisnadineSilybinForskolinPaclitaxelCamptothecin
ActivityNarcotic analgesicAntitussiveAntitussive, narcotic analgesicSmooth muscle relaxantCNS stimulantAmebicideAntimalarialAntiarrhytmicCNS stimulantAntinflammatory (gout)AnalgesicAnticholinergic, mydriaticSmooth muscle relaxantTopical anestheticCholinergicAntiglaucoma, mioticAnticholinergicAnticholinergicSympathomimeticCardiotonicAntiarrhytmicAntihypertensiveAntihypertensiveSkeletal muscle relaxantAntitumorAntitumorCoronary vasodilatorAntitoxic, liver protectantAdenylate cyclase stimulatorAntitumorAntitumor
Year of Isolation1806181718321848181718171819183318191820182918311842186018641875188118811897193019311952195419351952195819611968197719911993
PLANT DERIVED ACTIVE AGENTS
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PlantAgave sisalana (Engelm.) J.R. Drumm et Prain
Dioscorea sp.
Glycine max. (L.) Merr. (Soya bean)
Colchicum autumnale L.
Gloriosa superba L.
Podophyllum peltatum L.
Solanum sp.
Catharantus roseus (L.) G. Don (aerial parts)
Catharantus roseus (L.) G. Don (roots)
Synthone Agent
Ipomoea hederacea Jacq.
hecogenin
diosgenin
stigmasterol
colchicine
colchicine
podophyllotoxin
solasodine
anhydrovinblastine
serpentine
lysergol
corticosteroids
corticosteroids, sex hormones
thiocolchicoside
thiocolchicoside
etoposide, teniposide
Taxus baccata L. (leaves) 10-deacetylbaccatin III taxol, taxotère
navelbine
raubasine
nicergoline, pergolide
Voacanga africana Stapf. tabersonine vincamine, vinpocetine
corticosteroids, sex hormones
corticosteroids, sex hormones
Camptotheca acuminata L. camptothecin topotecan, irinotecan
ACTIVE AGENTS FROM PLANT DERIVED SYNTHONES
Taxus baccata L. (leaves) 10-deacetylbaccatin III taxol, taxotère
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10-deacetylbaccatin III
O
OH
OOHO
HO
HO
OO
10
13
7
14
O
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Paclitaxel R1= COC6H5 ; R2= CH3CODocetaxel R1= COOC(CH3)3 ; R2= H
O
OH
OOHO
OR2O
O
OO
O
OH
R1NH13
107
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IDN 5109Licensed to Bayer and currently in Phase II
O
OH
OOO
OAcO
O
OO
O
OH
NH
O
O
OO
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O
OH
OOHO
OHO
O
O
O
NH
OH
O
O O
Molecular Formula : C41H57NO14 M.W.: 787.38
NSC Number : 718373
[α]D = -51.0° (c= 1%, MeOH)
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ANTITUMOR ACTIVITY OF IDN 5390ORALLY ADMINISTERED
IN MAMMARY CARCINOMA MX-1
Days after tumor implantation
Tum
or w
eigh
t (m
g)
0 10 20 30 40 50 60
1000
100
10
Control120 mg/kg qd5/w x 3 weeks 30 mg/kg 2qd5/w x 3 weeks
90 mg/kg 2qd5/w x 5 weeks 60 mg/kg 2qd5/w x 3 weeks
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ANTINEOPLASTIC ACTIVITY OF IDN 5390ON 1A9/PTX22 HUMAN OVARIAN CARCINOMA
IDN 5390 120 mg/kg i.p. q1x5 for two weeks
0 10 15 20 25 30Days after tumor transplantation
Med
ian
tum
or w
eigh
t (g)
0.0
0.5
1.0
1.5
2.0
Treatment
Control
IDN 5390
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Antitumor effect of oral IDN 5109 and IDN 5390,alone or in combination in Taconic SCID mice
implanted with human colon tumor xenograft, DLD-1
0 5 10 15 20 25 30 35 40 45 50 55 60 65
Med
ian
Tum
or V
olum
e (m
m3 )
0
200
400
600
800
1000
1200
1400
Days after DLD-1 tumor implant
Control
Vehicle Control IDN 5109 90 mg/kg (q7dx3)IDN 5390 60 mg/kg (qdx5/w x 4 weeks)
IDN 5109 270 mg/kg+ IDN 5390 1800 mg/kg
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IDN 5390(NEW ANTICANCER DRUG)
Semisynthetic taxane derivative with modified baccatin skeleton•
Different mechanism of action•
Initially selected as inhibitor of angiogenesis it is endowed withan unknown mechanism
•
Active orally after chronical administration in several tumorxenograft and metastasis
•
Active on Paclitaxel-resistant cell lines•
Devoid of toxicity in repeated administration as body weight loss•
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SELECTED ACTIVE PRINCIPLES AND HIGH CONTENT STANDARDIZED EXTRACTS FROM PLANTS
60% asiatic and madecassic acids,40% asiaticoside
70% flavonoids calculated as silybin
36% anthocyanosides
24% total ginkgoflavonglycosides,6% ginkgolides and bilobalide
14% ginsenosides as ginsenoside Rg1
25% hydroxyanthracene diglycosidescalculated as cascaroside A
95% polyphenols
45% sennosides calculated as sennoside B
13% total sterols calculated as ß-sitosterols
90% C8 to C20 linear chain fatty acids
0.3% hypericin
20% proanthocyanidins
3% luteolins glycosides
STANDARDIZATIONSelected triterpenes
Purified dry extract (silymarin)
Dry extract (Myrtocyan )
Dry extract
Dry extract
Selected hydroxyanthracene glycoside(Purselect ; Casanthranol)
Purified dry extract (LEUCOSELECTTM)
Purified dry extract
Purified soft extract
Purified extract
Methanolic extrac
Ethanolic extract
Ethanolic extract
PRODUCTCentella asiatica (L.) Urban
Silybum marianum (L.) Gaertn.
Vaccinium myrtillus L.
Ginkgo biloba L.
Panax ginseng C.A. Meyer
Rhamnus purshiana DC
Vitis vinifera L.
Senna alexandrina Miller
Prunus africana (Hook. f.) Kalkm
Serenoa repens (Bartr.) Small
Hypericum perforatum L.
Crataegus oxyacantha L.
Cynara scolymus L.
PLANTSerial parts
Fruits
Fruits
Leaves
Roots
Bark
Seeds
Leaves
Bark
Fruits
Leaves-flowers
Leaves-flowers
Leaves
PART
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BIOLOGICALLY ACTIVE COMPOUNDSFROM PLANT KINGDOM
PURE PRINCIPLES MULTI COMPONENTS(raw drug, tinctures ...)
PHARMACEUTICAL MARKET
STANDARDIZED EXTRACTS,SELECTED FRACTIONS ...
PURE PRINCIPLES
DIETARYSUPPLEMENTS
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F. Lang, H. Stumpf, PHARMEUROPA Vol. 11, No. 2, 268, June 1999 (adapted)
extract fillingheight
velocity offlow
staticalpressure
batchsize
method ofextraction
time ofextraction
extractiontemperature
extractionpressure
nature ofplant material
part ofplant material
origin ofplant material
degree ofprocessing
watercontent
nature ofsolvent
concentration ofsolvent
amount ofsolvent
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STANDARDISATION
EMEA/HMPWG/9/99
Standardisation means adjusting the herbal drugpreparation to a defined content of a constituent or a groupof substances with known therapeutic activity respectivelyby adding excipients or by mixing herbal drugs or herbaldrug preparations (e.g. standardised extracts from theEuropean Pharmacopoeia).
*
* In some Member States the expression is used to describe all measures whichare taken during the manufacturing process and Quality Control leading to areproducible quality.
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STANDARDISATIONPLANT MATERIAL QUALITY1.
MANUFACTURING PROCESS2.
IN PROCESS CONTROLS3.
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GENERAL MANUFACTURING PROCESS SEQUENCE
QuarantineBIOMASSReleased / RejectedQUALITY CONTROL
GRINDINGEXTRACTIONPURIFICATION
QuarantineDRYINGReleased / RejectedQUALITY CONTROL
SHIPPING
In-process controls
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GAPPRINCIPLES AND GUIDELINES FOR GOOD AGRICULTURAL PRACTICE
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SEEDS AND PROPAGATION MATERIAL1.
Materials have to be identified botanically indicatingplant variety, cultivar, chemotype and origin.
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CULTIVATION2.
Depending on the mode of cultivation e.g.conventional or organic, growers should be allowedto follow different SOP. In general, care should betaken to avoid environmental disturbances.The principles of good crop husbandry must befollowed including an appropriate rotation of crops.
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HARVEST3.
Harvesting modalities and equipment have to bedescribed in details.
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PRIMARY PROCESSING4.
Primary processing includes steps of processingsuch as washing, freezing, distilling, drying etc.All these processes whether for food or medicinaluse must conform to relevant European andNational Regulation.
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PACKAGING5.
Modalities of packaging have to be described indetails.
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STORAGE AND TRANSPORT6.
Modalities of storage, including dose for fresh andfrozen product have to be described in details.
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EQUIPMENT7.
PERSONAL AND FACILITIES8.
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Any starting material and processing steps have tobe documented, including the location of
cultivation.Each batch must have a Batch Packaging Record.Any mixing procedures should be documented byBatch Processing Records.
DOCUMENTATION9.
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EDUCATION10.
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Agreement between producers and buyers ofmedicinal and aromatic plants, with regard toquality issues, must be based on internationallyrecognized or national specifications and shouldbe documented in a written way.
QUALITY ASSURANCE11.
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Self inspection should be conducted in order tomonitor the implementation and compliance withGAP. principles and to propose necessarycorrective measures.
SELF INSPECTION12.
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Q7A
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Q7A- GMP Concept• GMP controls apply to all steps in the
manufacturing process beginningwith the use of starting materials
• Only critical manufacturing steps aresubject to process validation
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1. Introduction
2. Quality management
3. Personnel
4. Building and facilities
5. Process equipment
6. Documentation and records
7. Materials management
8. Production and in-process controls
9. Packaging and labelling
10. Storage and distribution
11. Laboratory controls
12. Validation
13. Change control
14. Rejection and reuse of materials
15. Complaints and recalls
16. Contract manufacturers and laboratories
17. API agents, brokers, distributors, repackers, and relabellers
18. Special biotech consideration
19. APIs for clinical trials
20. Glossary
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13. Change control
Change control is a pivotal point.Every changement has to be evaluated inadvance also in relation to the industrial
impact.Normally in QA Departments a whole unit isdevoted to this particular problem.When the changement does not fit withacceptable criteria it is rejected.
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GAP and GMP (ICH-Q7A)
allows the
correct standardisation of
pharmaceutical botanical derivatives
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Echinacea angustifolia
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E. paradoxa var. par.
E. angustifolia var. ang.
E. sanguinea
E. pallida
GENUS ECHINACEA
E. simulata
E. purpurea
E. atrorubens
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CONFUSION
1. Leaves broadly to narrowly ovate, rounded at base, often serrate:
Echinacea purpurea
1. Leaves lanceolate to linear lanceolate. Attenuate to base, never serrate:
2. Ligules 4-9 cm long, white pollen: Echinacea pallida
2. Ligules 2-4 cm long, bright yellow pollen, compact growth habit,
max 0,5 m height: Echinacea angustifolia
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CHEMICAL DIFFERENCES
Minutes5,00 10,00 15,00 20,00 25,00 30,00 35,00 40,00 45,00 50,00 55,00 60,00
Minutes10,00 20,00 30,00 40,00 50,00 60,00
EchinacosideAlkamide 8
E. angustifolia
E. pallidaEchinacoside
Cichoric acidAlkamide 8E. purpurea
Pentadeca-8Z-en-2-one
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E. ANGUSTIFOLIATHE SELECTION: FIRST STEP
ANALYSIS
Polysaccharides %
Echinacoside %
Isobutylamides %
Resistance to parasites
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IN VITROMICROPROPAGATION
SELECTED
PLANTS
E. ANGUSTIFOLIATHE SELECTION: SECOND STEP
CLONES
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CULTIVATION AND PRODUCTION OF SEEDS
E. ANGUSTIFOLIATHE SELECTION: THIRD STEP
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LARGE SCALE CULTIVATION
E. ANGUSTIFOLIA
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BIOMASSFOREXTRACTION
FURTHER SELECTIONS AND MICROPROPAGATIONS
LARGE SCALE CULTIVATION
E. ANGUSTIFOLIA
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Echinacea angustifolia rootsFirst hydroalcoholic extraction (for echinacoside)
Enriched extract(echinacoside)
Hydroalcoholic extract
Enriched extract(IDN 5405)
Second hydroalcoholicextraction
(for IDN 5405)
™
Wet plant material
Enriched fraction(isobutylamides)
n-hexanecounter-extraction
(for isobutylamides)
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™
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™
HO
CH CH COOHO OCH2
OCH2O
H
O
HO
HOOH
OHO O CH2 CH2
OH
OH
HO
O
HO
H3C
OH
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O
OH
HO
OH
OH O
O
OH
OH
OH
CH2
O
O
OH
OH
OH
CH2
n
HO
LOW MOLECULAR WEIGHT POLYSACCHARIDE
Structure of inulin (fructose polymer)
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hairy regionshairy regions
smooth regions
O
O
O
O
O
O CO2Me
HO
OH
HO
CO2H
OHCO2Ac
HO
OHO
smooth regions
The high molecular weight
polysaccharide is a methoxy pectin
with a backbone of
α-(1-4) polygalacturonic acid
partially carboxymethylated (about 60%)
and partially acetylated (about 9%)
(smooth region) and with hairy region of
substituted rhamnogalacturonan.
IDN 5405HIGH MOLECULAR WEIGHT POLYSACCHARIDE
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POLYSACCHARIDES PROFILE
HIGH MOLECULAR
WEIGHT
LOW MOLECULAR
WEIGHT
IDN 5405
Inulin
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ISOBUTYLAMIDES INECHINACEA ANGUSTIFOLIA ROOTS LIPOPHILIC EXTRACT
1 3 6
2 54
7 8
9
1210,11
1314
0 10 20 min
1) Undeca-2E,4Z-dien-8,10-diynoic acid isobutylamide2) Undeca-2E-en-8,10-diynoic acid isobutylamide3) Undeca-2Z,4E-dien-8,10-diynoic acid isobutylamide4) Undeca-2Z-en-8,10-diynoic acid isobutylamide5) Dodeca-2E-en-8,10-diynoic acid isobutylamide6) Trideca-2E,7Z-dien-10,12-diynoic acid isobutylamide7) Dodeca-2E,4Z,10Z-trien-8-ynoic acid isobutylamide
8) Undeca-2Z-en-8,10-diynoic acid 2-methylbutylamide9) Dodeca-2E-en-8,10-diynoic acid 2-methylbutylamide
10) Dodeca-2E,4E-8Z,10E-tetraenoic acid isobutylamide11) Dodeca-2E,4E-8Z,10Z-tetraenoic acid isobutylamide12) Pentadeca-2E,9Z-dien-12,14-diynoic acid isobutylamide13) Hexadeca-2E,9Z-dien-12,14-diynoic acid isobutylamide11) Dodeca-2E,4E-dienoic acid isobutylamide
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OD
550
/650
0.5
0.4
0.3
0.2
0.1
0.0
0.6
0.8
0.7
Vehicle 11.1 33.3 100
Medium
Con A
µg/mL
CYTOTOXIC EFFECT ON MURINE SPLENOCYTES INDUCEDBY INCREASING CONCENTRATIONS OF ECHINACEA
ANGUSTIFOLIA ROOTS LIPOPHILIC EXTRACT
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OD
550
/650
0.5
0.4
0.3
0.2
0.1
0.0
0.6
0.8
0.7
Vehicle 11.1 33.3 100
Medium
LPS
µg/mL
CYTOTOXIC EFFECT ON MURINE SPLENOCYTES INDUCEDBY INCREASING CONCENTRATIONS OF ECHINACEA
ANGUSTIFOLIA ROOTS LIPOPHILIC EXTRACT
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EFFECT OF ECHINACEA ANGUSTIFOLIA ROOTS LIPOPHILIC EXTRACT
ON INTESTINAL MOTILITY IN MICE
Male Swiss mice (25-30 g) were fed on a charcoal meal (5% in 5% arabic gum).Animals were fasted for 3 hours before intraperitoneal administration of the compound.
Upp
er g
astr
oint
estin
al tr
ansi
t (%
) 60
50
40
30
20
10
0Control
p <0.01
**
E. ANGUSTIFOLIA ROOTS LIPOPHILIC EXTRACT5 mg/kg i.p.
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ADDITIONAL INFORMATION ONECHINACEA ANGUSTIFOLIA ROOTS
LIPOPHILIC EXTRACT
Acute oral toxicity in mice: 236 mg/kg (LD50)
Electrophysiological experiments in rat sciaticnerve-EDL muscle: effects on nerve impulseand synaptic transmission
√
√
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EFFECT OF Polinacea™ (ORAL ADMINISTRATION)ON IMMUNOCOMPETENT AND IMMUNOSUPPRESSED
CANDIDA ALBICANS INFECTED MICE
Treatment
Candida albicans (350,000 / i.v. / mouse)
Candida albicans + Polinacea™ (20 mg/mouse)
Candida albicans + Cyclosporin A (1 mg/mouse)
Candida albicans + Cyclosporin A + Polinacea™
Survivorsafter 10 days
20
20
10
10
0
6
0
4
n
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Treatment Survivorsafter 13 days
Candida albicans 10 0
Candida albicans + Echinacin® 10 0
Candida albicans + LPS (40 ng/mouse) 10 1
Candida albicans + Polinacea™ (2 mg/mouse) 10 4
n
EFFECT OF Polinacea™ (I.P. ADMINISTRATION)ON IMMUNOCOMPETENT
CANDIDA ALBICANS INFECTED MICE
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Control
100 µg/mL
10 µg/mLPolinacea™
LPS [ 1 µg/mL ]
5
3
3
3
Interferon-γ
56
45
79
15
Co-treatment ----- [ 1000 U/mL ]
1 µg/mL 3 21
0.01 µg/mL 3 11
(LPS : 200 ppm)
NO (µM) PRODUCTION BY J774 AFTER 48 HOURS OF TREATMENT
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Control
Polinacea™
LPS [ 1 µg/mL ] 5.4
0
Interferon-γ
100 µg/mL 0 24.6
10 µg/mL 0 20.9
49.3
21.8
Co-treatment ----- [ 500 U/mL ]
1 µg/mL 0 21.4
0.1 µg/mL 0 16.1
0.01 µg/mL 0 25.9
NO (µM) PRODUCTION BY J774 AFTER 48 HOURS OF TREATMENT( ALL SAMPLES ARE LPS FREE)
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Control
IDN 5405
LPS [ 1 µg/mL ] 6.4
0
Interferon-γ
100 µg/mL toxic toxic
10 µg/mL 0 18.0
50.0
16.8
Co-treatment ----- [ 500 U/mL ]
1 µg/mL 0 16.0
0.1 µg/mL 0 17.8
0.01 µg/mL 0 17.7
(high molecular weight polysaccharides)
NO (µM) PRODUCTION BY J774 AFTER 48 HOURS OF TREATMENT( ALL SAMPLES ARE LPS FREE)
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Control
Inulin
LPS [ 1 µg/mL ] 14.6
0
Interferon-γ
100 µg/mL 0 10.0 (toxic)
10 µg/mL 0 13.9 (toxic)
51.8
24.6
Co-treatment ----- [ 500 U/mL ]
1 µg/mL 0 20.4
0.1 µg/mL 0 20.2
0.01 µg/mL 0 19.3
(low molecular weight polysaccharide)
NO (µM) PRODUCTION BY J774 AFTER 48 HOURS OF TREATMENT( ALL SAMPLES ARE LPS FREE)
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PURIFIED SPLEEN T LYMPHOCYTES:IFN-γ PRODUCTION
3-wells mean values
Treatment 10 µg/mL 1 µg/mL 0.1 µg/mL
Medium ( 4.5 ± 0.5 )
αCD3 + IDN 5405
αCD3 + Polinacea™
αCD3 ( 149.5 ± 25.0 )
( ALL SAMPLES ARE LPS FREE)
690.5 ± 95.5
442.0 ± 70.5
466.3 ± 71.8
355.8 ± 61.4
410.0 ± 45.7
280.0 ± 35.8
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MILESTONESSELECTED CULTIVATED ECHINACEA ANGUSTIFOLIA PLANTS
™
UNIQUE TRIPLE STANDARDIZATION
LOW LEVEL OF ISOBUTYLAMIDES
INNOVATIVE EXTRACTION PROCEDURE
DIRECT IMMUNOLOGICAL EFFECT ON T CELLS
WELL TOLERATED IN ACUTE AND SUBACUTE TOXICITY
IDEAL CANDIDATE FOR CLINICAL TESTING
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Hypericum perforatum L.
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0 20 40 60min
HPLC chromatogram of ST. JOHNSELECT™ (LI 160)
1
23
4 5
6
7
8 9
10
11
12
15
13
1-3 Chlorogenic acid analogues4-6,8,9 Flavonol derivatives7 Pentahydroxyflavanone10 I3,II8 Biapigenin11,12 Hypericin analogues13-16 Hyperforin analogues
14
16
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ST. JOHNSELECT™ (LI 160)PERCENTAGE AMOUNT OF MAIN COMPONENTS
3.393.424.882.290.560.290.360.340.204.500.61
Percent (HPLC analysis)
Chlorogenic acidRutin
HyperosideIsoquercitrin
QuercitrinQuercetin
I3,II8 BiapigeninPseudohypericin
HypericinHyperforin
Adhyperforin
Component
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From: BMJ 313, 253-258 (1996)
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From: Linde K., Ramirèz G., Mulrow C.D., Pauls A., Weidenhammer W., Melchart D., BMJ 313, 253-258 (1996)
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continue
From: Linde K., Ramirèz G., Mulrow C.D., Pauls A., Weidenhammer W., Melchart D., BMJ 313, 253-258 (1996)
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VARIATION OF ANALYTICAL PARAMETERS OF ST. JOHN’S WORT PLANT MATERIAL AND PREPARATIONS
3.9 : 14.3 : 13.7 : 13.4 : 13.4 : 14.7 : 14.7 : 15.4 : 13.1 : 1
drug-extract-ratio
123456789
Lot
0.240.270.230.460.430.360.220.170.35
contentof
hypericin
0.581.551.843.523.857.778.309.59
13.68
contentof
hyperforin
preparations
content given as % values
0.0600.0620.0630.1360.1270.0760.0470.0320.122
0.1500.3610.4971.0351.1321.6531.7671.7765.025
contentof
hyperforin
plant materialcontent
ofhypericin
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COMPARATIVE 13C-NMR OF TWOHYPERICUM PERFORATUM EXTRACTS
200 180 160 140 120 100 80 60 40 20 ppm
INDENA HYPERICUM PERFORATUM EXTRACTCOMMERCIAL HYPERICUM PERFORATUM EXTRACT
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COMPARATIVE 1H-NMR OF TWOHYPERICUM PERFORATUM EXTRACTS
INDENA HYPERICUM PERFORATUM EXTRACTCOMMERCIAL HYPERICUM PERFORATUM EXTRACT
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Characterization of Hypericum perforatum extracts byNIR (Near infrared spectroscopy)
H. PERFORATUM EXTRACT FROM DIFFERENT PRODUCERS
INDENA H. PERFORATUM STANDARDIZED EXTRACT
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CONCLUSIONS
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Standardisation of botanical derivatives according to GAP
and GMP (ICH Q7A) is the only procedure which
guarantees:
- the reproducibility of pharmacological and clinical effects;
- the complete assurance of reproducibility of safety.
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Phytoequivalence can be evaluated by
combining classical analytical determination
(spectrophotometric, GC, HPLC) of known
products (markers, active principles) with an
innovative spectroscopic approach (13C-NMR,1H-NMR and NIR) which allows the qualitative
evaluation of the globality of the extracts.