neem product development : opportunities and...
TRANSCRIPT
NEEM PRODUCT DEVELOPMENT : OPPORTUNITIES AND CHALLENGES
Structure of Presentation
A story
Experiences
Changing Landscape
Page Numbers 207-223
Dr. Gopinathan M .C
E I D PARRY( INDIA) LTD
JOURNEY OF NEEM
?HINDU TEXTS
TRADITIONAL
MEDICINE
SILVER LINE
GOLDEN ERA
Medicinal properties illustrated since ‘Vedic Times’Acknowledged as a “cardiac tonic”
‘Kautilya’ mentioned Neem in his ARTHASHASTRA : “The science of economy & commerce”Gained an indispensable position in the traditional medicinal systems: Ayurveda, SIDDHA & UNANI
Neem migrated to over 24 countries by immigrants & travelers
Muslim voyagers & colonizers conferred the title ‘Azad dirahth-i-hind’ -Noble/Free of India upon neem
From the title -‘free tree of India’, Neem continued to grow as- ‘free tree of the World’
Year 1968 marked by structure elucidation of Azadirachtin
Scientific investigations re-established Insecticide properties of Azadirachtin
27 classes of biological properties revalidated from traditional treatises
Presence of 116 active limonoids found in neem
285 scientific papers published on pesticide property of neem
430 patents claimed worldwide
98 product brands created in various applications
421 pesticide formulations available for pest control of Agri-horticulture crop segments
Ideal fit with the IPM or Certified Organic
Philosophers
Emperor Asoka
People
BiologistsChemists
AdministratorsInvestors
Profitability from neem business & re-emergence Global opportunities
4000 BC 4th Century BC 10th Century 20th Century 21st Century
Neem Tree Journey
ASIAIndia
MyanmarBangladesh
ChinaSri LankaPakistan
NORTHAMERICA
FloridaArizona
South CaliforniaOklahoma
MexicoMiami
Cost RicaPanama
AFRICASaudi Arabia
Iran
Qatar
Yemen
Somalia
Ethiopia
Madagascar
Sudan
Kenya
Nigeria
Tanzania
Mauritius
Ghana
Ivory Coast
SOUTH PACIFICAustralia
Papua New Guinea
Fiji Islands
Hawaii
Indonesia
Philippines
SOUTH AMERICA
Brazil
Cuba
Jamaica
Surinam
Guyana
Haiti
AzadirachtinA, Azadirachtin B, Salannin, Salannol, Azadirone, Azadiradione, epoxyazadiradione, nimbandiol, 6-acetyl nimbandiol, nimbinene, 6-deacetylnimbinene, 1,3-diacetylvilasinin
Antihypoglycemic, Antiseptic, Spermicidal, Antifertility, Antidandruff, Ectoparacite, Personalcare, Mosquito repellent, Pesticidal, Larvicidal, Disinfectant
Oil
Sodium nimbidate, Azadirachtin A,BDEFGHIJ-K, 17-Epiazadiradione, 17-b-hydroxynimbocinol, 7-deacetyl-7- benzoylnimbinin, 1b,2b-epoxy- nimbinin, 1-tigloyl-3-acetylvilasinin, 1-tigloyl-3- acetyl- 12a-acetoxyvilasinin, nimbin, 6-acetyl nimbin, ohchinolide B, 21-oxo-ohchinolide B, salannin, 6-deacetylsalannin, salannolacetate, salnnolactum-21, salannolactum-23, 2',3'dihydroazadirachtin B, azadirachtol, 22,23-dihydroazadirachtin B, vepaolmarragin, b-nimolactone,
Diuretic. Antigastric. Antipyretic. Antiinflammatory. Antifungal. Nematicidal. Larvicidal. Ectoparacitidal. PesticidalSeed
Nimocinol.eldin,azadirone,Nimbcinol,isonimbocinide,Arachidic acid, Azhadiractol, Myristic acid .Nimolicinol, Polysaccharides
Anti-inflammatory, Antitumor. DentifriceBactericidal . nematicidal . PesticidalFruits
Beta sitosterol,Kaempferol.Myrcetin ,QuercetinPitta (balancing of the body heat) and kapha(cough formation) astringent, antihelmintic.Flowers
Gedunin, 7-Deacetylgedunin, 7-Deacetyl- 7-benzoylgedunin, 6-Deacetylnimbin, epiazadirone, Nimbin, Nimninin,Ninbidine,Nimbine, Nimbione, Nimbosterol, Nimbionine.Polysaccharide
Astringent, acrid , refrigerant, useful in tiredness, cough, fever, loss of appetite, worm infestations. heals wounds , control vomiting, skin diseases, excessive thirst. dental care, treatment of leprosy, spermatorrhea, analgestic, antiantiinflamtory, antifertility.
Bark
Nimbandiol, 6-Acetylnimbandiol, 6-Acetyl- niminene, Nimbolide, 28-Deoxonimbolide, Nimbin, 6-Deacetylnimbin, 6-Deacetylnimbal, 4a,6a-Dihydroxyhomoazadirone, 6-Deacetylnimbinene, Nimocinolide, nimbidic acid, Kaempferol, Quercetin
Antidiabetic, Antifertility, Antimalarial, Antimicrobial, Antiviral, Antihepatitus, Personal Care, Immunostimulant, Wormicidal, Repellent, Pesticidal, Nematicidal, Larvicidal, protectant for stored grain pests
Leaves
Diverse, part specific compounds with multipurpose application and uses
571
450
404
205 199187
84 7449
219
0
100
200
300
400
500
600
Num
ber o
f Pub
licat
ions
Oil Seed Leaf Bark Fruit wood Flower Cake Pulp Root Twig
Research Publications on Neem- Various parts *Reports, General article etc not included
Validation through Research
Research Publications on Neem- Biological Properties 445
158
64 5955 44 39 37 36 36 32 31 29 28 26 26 23 20 20 19 11 10 10 9 8 4 4
0
50
100
150
200
250
300
350
400
450N
umbe
r of P
ublic
atio
ns
InsecticidalOral careAnticancerAntibacterialAntifungalAntifertilityAntipyreticAntiparasiteDiabeticAnti inflam
matory
LarvicidalAntiviralOvicidalAntim
alarialAnti ulcersDental CareAntidiureticAntioxidantAntim
osquitoNem
aticidalIm
munostim
ulantAnticarcinogenRepellantIm
munom
odulatingAntiliceAntisepticPersonal Care
*Reports, General article etc not included
Validation through Research
AZAD
IRO
NE, 1
9
GED
UNIN
, 4
VILA
SINI
N, 5
C SECO MELIACINS, 14
Nim
bin,
6Ni
mbo
line,
2 Sala
nnin
, 6
AZADIRACHTINS, 15
Azad
irach
tols
, 6 Azad
irach
tin, 6
Mel
iaca
rpin
, 1
Azad
irach
tinin
s, 1
Mel
iaca
rpin
ins,
1
OTH
ER T
RITE
RPIN
OID
S, 6
DITE
RPIN
OID
S, 3
NONT
ERPI
NOID
S, 7
05
1015
20
116 Biologically active structure identified Limnoids
Am
oorastatin
Vepinin
Chemical constituents of Neem
Confirmation of Active Principles
PESTICIDAL
Research Publications Chemical Constituents of Neem634
9878
42 33 31 28 13 12 12 10 9 9 8 8 5 2
0
100
200
300
400
500
600
700N
umbe
r of P
ublic
atio
ns
AzadirachtinsNim
binG
eduninNim
bolideM
eliacinsNim
bidininAzadironeNim
bininBeta-sitosterolNim
bidinateAzadirachtininsAzadirachtolsSalanninM
eliacarpininsVilasininNim
bidolM
ahmoodin
Reports, General article etc not included
Shifting Focus
PESTICIDAL
Research Publications on Azadirachtin- Applications
285
210
4027
15 144
0
50
100
150
200
250
300N
umbe
r of P
ublic
atio
ns
Pesticidal
Chemistry
Medicinal
Product Development
Manufacturing
Synthesis
Herbal remedies
Patents on Neem
12 2 1
3 2 13
7 6
1113
10
3432
25
40
23
26
23
27
32
36
22
31
22
0
5
10
15
20
25
30
35
40
197980 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 2000200120022003200420052006
Entry Barriers, international conflicts and increased investments
GOLDEN ERA
*Trilateral and PCT Database
---11Singapore
48135186236434Total
OthersVeterinaryProcessPharmaceuticals Agriculture
---213Republic of Korea
---134Mexico
1-1316United Kingdom
1-2249Others
2122815China
1-2912EP
11-4814Germany
1221015New Zealand
-2851631Australia
6-562037PCT
713123053Japan
1055102959Canada
6311194281USA
12-12155594India
ApplicationsTotal No. of Patents
Country
Number of patents related to process and product development of Neem
PERSONALHYGIENE
SoapsShaving Cream
ToothpasteTooth powder
Medicated soap for acneBody lotions
NEEM ShampooNEEM hair oil
NEEM Hair conditionersNEEM hair rejuvenating tonics
NEEM MouthwashFace wash gel
Skin tonerCleansing milkWashing gelAntibacterialDisinfectant
Detergent SprayAir PurifierFace Scrub
Anti liceDeodorant
Anti dandruff
HERBAL DRUGSNEEM Tablets
AntifungalAntibacterial
CapsulesNEEM Tea
Rejuvenating Anti StressDetox and weight loss
Blood rectifier tonicNeuro stimulant
Diabetics & PancreasArthritis Oil
Various categories of Neem products in the market
COSMETIC PRODUCTSNEEM Lip balmNEEM eye gel
NEEM Night CreamMoisturing CreamFace Wash Gel
Body ScrubBody massage oil
Face ScrubFace pack
Facial massage oilSunscreen lotion
Cleansing gelPedicurePowderHair Gel
VET CARE PRODUCTSPet Shampoo
Lice SprayPowders
NEEM Scabies pet careSoap
AGRICULTURAL PRODUCTS PesticidesFertilizersManures
Urea Coating agentSoil conditioners
Bio control agentsPruning paste
AESTHETIC PRODUCTSIncense Sticks
NEEM CoirNEEM Candles
NEEM Room freshener
OTHER PRODUCTSCockroach Repellent Mosquito Repellent
Insect Repellent
Neem formulations registered under Central Insecticide Board, India
221
78 71
45
5 1
0
50
100
150
200
250
Num
ber o
f For
mul
ator
s
0.03 - 0.15 %(Aza)
formulations
0.3 - 0.5 %(Aza)
formulations
1.0 % (Aza)formulations
5.0 % (Aza)formulations
10 %Technical
extract
>25 %Technical
extract
Why do we haveonly few Technical
Manufactures ?
Idea to market
0
10
20
30
40
50
60
No. O
F PAT
ENTS
USA
INDIA
AUST
RALIA
CANA
DA EPO
JAPA
N WO
OTHE
RS
GERM
ANY
NEW
ZEAL
AND UK GR
NEEM PATENTS - GLOBAL STATUS
Others
FoodVeterinary care
Health carePharmaceuticals
Pesticides
56
38
2321 21
1512 12 10
8 6 4
Entry BarrierPatentsLicensed Licensed
Novel LabNovel LabProcessProcess
Pilot Plant
M. Plant Product development
RegistrationIndia/AbroadRaw material
CollectionLogisticStorageQualityPlantationTissue culture
Delivery mechanismEco friendlyBio efficacy
Design&DevelopmentUp scalingAutomationEfficiency
1990 20061992
1993
1998
1994
India1996Germany1998USA 2001Other 25 countries
1995
28 countries
Multi disciple. R&D
In house trialsRegulatory trialsToxicology trialsFarmer field trials
DemonstrationTest MarketingConcept sellingExports
Market
Bio-efficacy spectrum reported worldwide on NEEMAZAL and its formulations against various crop pests
TotalPoorAverageGoodExcellent
868394112189534223Total
874706172410Thrips
912302194816355Caterpillars & Borers
863250457021077Sucking Pests (Jassids,BPH,Aphids etc)
8061012143524Files (Fruitflies,leafminers etc)
7699222126343Beetles & Weevils
897508283914Mites
% of Good &above
Publications & Reports*No. of Species reported
Category of Pests
*Excellent – >80%; Good->70%; Average-> 50%; Poor-<30%
NA
TION
AL N
ETWO
RK
S
INTER
NA
TION
AL N
ETWO
RK
S
Field /Lab experimental results
NOEC 100 mg/ literEcotoxicology – Rainbow Trout
No Immobilization at 666.7 mg/liter (24 hrs)Ecotoxicology – Daphnia (Immobilization)
NOEC (0 – 72 hrs) 22 mg/ literEcotoxicology - Algae
NOEL 1000 mg/ kg body wt. Reproductive Toxicity, Rat
NOAEL 500 mg/ kg body wt. Teratogenicity, Rat
NOAEL 50 mg / kg body wt. Developmental Toxicity, Rat
No chromosome damageMicronucleus test, Mouse bone marrow
Non mutagenicMammalian Cell gene mutation
Non mutagenicMutagenicity, in vitro, Salmonella typhimurium
Non mutagenicMutagenicity, in vivo, Mice
Non carcinogenicCarcinogenicity, Rat
NOEL 100 ppm feedSub Chronic Toxicity, Rat (90 days)
SlightSkin sensitization, Guinea Pig
Slight at 70 mg, reversible on the 4th dayEye Irritation, Rabbit
SlightSkin Irritation, Rabbit
> 5000 mg / kg body wt. Acute Oral Toxicity, Mice (LD50)
> 0.72 mg / liter of air Acute Inhalation Toxicity, Rat (LD50)
> 2000 mg / kg body wt.Acute Dermal Toxicity, Rat (LD50)
> 5000 mg / kg body wt.Acute Oral Toxicity, Rat (LD50)
REGULATORY APPROVALS
INTER
NA
TION
ALG
UID
ELINES
NA
TION
AL R
ULES
DATA GENERATION IN GLP LABORATORIES
NEEMAZAL-Safety to Humans, Vertebrates, Beneficial's and ecology
Sodium Chloride - Acute Oral Toxicity – Rat (LD50) = 3000 mg / kg body wt.
NEEMAZAL- Journey
ASIAIndia China
Sri Lanka
NORTHAMERICA
USAMexico
Cost RicaChile
Honduras St Kitts
EUROPEGermany, Italy ,Netherlands
Austria, Slovania, Turkey
Estonia ,Bulgaria, Georgia
Spain ,France
SOUTH PACIFICAustralia
SOUTH AMERICA
Brazil
Argentina
Saudi ArabiaSouth Africa
Another 15 countries Registration Application is in Progress
AZADIRECT
Decreased mortality
Complete eradication
Increased life expectancy
Techn
ologie
sL
ife st
yle
Bio ,info andnano
Affluence Modern lifeWork habits Food habits Personal Habits Social habits
Graying planetsBrain &belly
evolutionHealth care
Millennium kids
ChallengesIncreased food production
Self sufficiency
Eradication of Poverty Green revolution
Agriculture
Big Brains and Hungry Hominids
• 170 million underweight children of which 3 million will die this year • One billion adults are overweight and at least 300 million are clinically
obese of which half million will die this year of obesity related diseases
In 1900 communicable diseases such as Pneumonia ,tuberculosis and diarrhea accounted 60% deaths in USA. In 2000 life style diseases accounted 60 % of all deaths
All other, 29
Respiratory, 16
Tuberculosis
Gastro
Heart, 8
Infectiouskidney
InfancyStroke
Cancer, 4Liver
All other, 20.3
Respiratory, 4.7
Heart, 31.4
Cancer, 23.3
Cerebral, 6.9HIVHomecideSuicideDiabetics, 2.7
0%10%20%30%40%50%60%70%80%90%
100%
1900 2000
In addition to the prospect of diminished health, obese people are often
stigmatized both socially and in the workplace.
This view is very dependent on the cultural context!
In many cultures, obesity is considered to be a sign of affluence and
prestige, particularly among those cultures where food is less available.
In modern times, however, intense pressure to be thin is felt by
most individuals, lean and obese.
CAN NEEM MEET THIS EXPECTATIONS ?
AZAD
IRO
NE, 1
9
GED
UNIN
, 4
VILA
SINI
N, 5
C SECO MELIACINS, 14
Nim
bin,
6Ni
mbo
line,
2 Sala
nnin
, 6
AZADIRACHTINS, 15
Azad
irach
tols
, 6 Azad
irach
tin, 6
Mel
iaca
rpin
, 1
Azad
irach
tinin
s, 1
Mel
iaca
rpin
ins,
1
OTH
ER T
RITE
RPIN
OID
S, 6
DITE
RPIN
OID
S, 3
NONT
ERPI
NOID
S, 7
05
1015
20
116 Biologically active structure identified Limnoids
Am
oorastatin
Vepinin
CHALLENGES OF PRODUCT DEVELOPMENTBiologists Pharmacologists Medical specialistsChemists
INHOUSE RESEARCH Formulators
Defined chemical entityMethod of analysis Stability/Combinatorial biosynthesis
SCIENTIFICEfficacy /ClinicalPharmo kinetic PatentsGenetics Breeding Pathways
Raw materialProduction Harvesting Storage Scale upAutomationQualityEconomicMarketingEntry barrier
ClinicalRegulatory
Safety
Toxicology
Consumer acceptance
BUSINESSPUBLIC
PARTNERS RESEARCH
NA
TIO
NA
L IN
STIT
UT
ES
INT
ER
NA
TIO
NA
L IN
STIT
UT
ES
Traditional practitioners Engineers/Process Technologists
Regulators
Certification Agencies
Investors
Adm
inistrators Financial Institutions
There is no single intervention that can establish to advance innovation, technology, economic growth and prosperity.
And it is our hope, however, that we can strive to create prosperity and wealth from this rich knowledge of Neem with realistic expectations for the future.
We can all be wealthy and healthy by efficient utilization of Neem knowledge.. But most important, is that we need to learn to work together “Holistically” forgetting our individual differences
