Download Memorandum 1188 ‘03 MAR13 1~48

DEPARTMENT
OF HEALTH
& HUMAN SERVICES
Public Health Service
Food and Drug Administration
Memorandum
1188
__
‘03 MAR13 1~48
Date:
March 7,2003
From:
Consumer Safety Officer, Division of Standards and Labeling Regulations, Office
of Nutritional Products, Labeling and Dietary Supplements, HFS-821
Subject:
75Day Premarket Notification of New Dietary Ingredients
To:
Dockets Management Branch, HFA-305
Subject of the Notification: Asmakure
Firm: Port Orchard Nutriceuticals
Date Received by FDA: December 9,2002
90-Day Date: March 9,2003
In accordance with the requirements of section 413(a) of the Federal Food, Drug, and
Cosmetic Act, the attached 75day premarket notification and related correspondence for the
aforementioned substance should be placed on public display in docket number 958-03 16.
Thank you for your assistance.
CSO/Lead Reviewer
Attachments
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Food and DNg Administration
College Park, MD
1189
'03 MAR13 P1:48
JamesKao, B. Pharm,MBA
Junwei Sun, M.S., MBA
Port Orchard Nutraceuticals
1800 Sidney Avenue l-203
Port Orchard, Washington 98366
Dear Mr. Kao
and Mr. Sun:
This is to inform you that the notification you submittedpursuantto 21 U.S.C. 35Ob(a)(2)was
received and filed by the Food and Drug Administration (FDA) on Dewmber 9,2002. Your
notification concernsthe substances,Abies Webbiana2.1 l%, Adhatoda Vasica 10.30%,
Zingiber officinale 6.27%, Piper Longum 8.25%, Piper nigrum 4.07% Cnmamomum
Zeylanicum 1.OO%,AmmomumSubulatum1.OO%,and Ntsadal 1.OO%under the name
Asmakure,and HemidesmusJndicus(Anantamul) 100 mg, Ricinus communis(Shetverenda)
100 mg, Moringa Pterygosperma(Sajina) 100 mg, Tinospora Cordifolia (Gulancha)125 mg,
and BoerhaaviaDiffusa (Rakta Punamaba)75 mg underthe namePanekurem that you assert
are new dietary ingredients.
The law at 21 U.S.C. 35Ob(a)(2)requiresthat a manufactureror distributor of a dietaty
supplementthat containsa new dietaryingredient submit certain information to FDA at least
75 daysbefore the dietary ingredientis introduced or deliveredfor introduction into interstate
commerce. This information must include the basison which the manufactureror distributor
has concludedthat a dietary supplementcontaining suchnew dietary ingredientwill
reasonablybe expectedto be safe. FDA reviews this information to determinewhether it
provides an adequatebasisfor such a conclusion. Under section 3SOb(a)(2),there must be a
history of use or other evidenceof safety establishingthat the dietary ingredient,when used
under the conditionsrecommendedor suggestedin the labelingof the dietary supplement,will
reasonablybe expectedto be safe. Jf this requirementis not met, the new dietary ingredientis
deemedto be adulteratedunder 21 U.S.C. 342(f)(l)(B), becausethere is inadequate
informationto provide reasonableassurancethat the new dietary ingredient does not presenta
significantor unreasonablerisk of ihnessand injury.
Federalregulationsfound at 21 CFR 190.6 specify the requirementsfor a premarket
notification on a new dietary ingredient. The notification you sentus concerningthe dietary
supplementswith tradenamesPanekurem and Asmakuredoes not comply with the
requirementsof 21 CFR 190.6 and is incomplete. For exampleit fails to:
Page 2 - Messrs.Kao and Sun
l
l
provide copiesof the referencesto publishedinformation offered in support of the
notification which shallbe reprints or photostaticcopiesof such references,also,if
any part of the materialsubmittedis in a foreign language,it shall be accompaniedby
an accurateand completeEnglish translation;
sufficiently describePanekuremand Asmakure(e.g., identify the Latin bmomial
namesof the botanicals(herbalingredients)includingthe genus,species,and the
(author) and any other known relevantpropertiesof the botanicalingredient(s)and all
relevantpropertiesof the mineralingredientNisdal, including its chemicalformula.
Accordingly, there is inadequateinformation in your notification for FDA to determine
whether there is an adequatebasisto concludethat the use of a dietary supplementthat
containsthe ingredientsidentifiedin your notification will reasonablybe expectedto be safe.
Therefore,your product may be adulteratedunder 21 U.S.C. 342(f)(l)(B) as a dietary
supplementthat containsnew dietary ingredient(s)for which there is inadequateinformation to
provide reasonableassurancethat it does not presenta significantor unreasonablerisk of
illnessor injury. Introduction of such products into interstatecommerceis prohibited under
21 U.S.C. 331(a)and(v).
~fyou wish, you may sendus the requiredinformation and addressthe issuesidentified above
to correct the deficienciesin your current notification in the form of an amendmentin triplicate
(i.e., an original and two copies). However, in order to serveas an amendmentto the current
notification, the information you submit must be deliveredto this office by no later than
February22,2003, which is 75 days after the current not&&ion’s Sling date. We note that if
the requiredinformation is not receivedwithin the 75&y timeframe,your notification will be
filed in the FDA’s Docket ManagementBranch 90 daysTom the effective filing date.
Another option is to sendus at any time a new notification, in triplicate, that is completeand
fidly complieswith 21 CFR 190.6. The datethat we receivethe additionali&ormation for
either an amendedor new notification is consideredthe new tiling date. Pleaseindicatein the
cover letter ifit is an amendedor new notification.
Your not&ation will be kept contidentialfor 90 days from the date of the e@ctive filing date.
After the 9Oday period, your notification will be placedon public displayat FDA’s Docket
ManagementBranch in docket number 958-0316. Prior to the 9Oday period, you may wish to
ident@ in writing specificallywhat information you believeis proprietary in your current
notification for FDA’s consideration
Page 3 - Messrs. Kao and Sun
For you information, the following FDA Internet sitesand their correspondinglinks may be
usefill:
http:kvww.cfsan.fda.gov/-dms/supplmnt.html
http://wwv.cfkan.fda.aovHrd/fB7923e.html (21 CFR 190.6)
pleasemdact me at (301) 436-2371,if you haveany questionsconcerningthis matter.
SusanJ. Walker, M.D.
Acting Division Director
Division of Dietary SupplementPrograms
and Compliance
Office of Nutritional Products,Labeling
and Dietary Supplements
Centerfor Food Safkty
and Applied Nutrition
Divisionof Standards
andLabelingRegulations
Of&iceof NutritionalProducts,L&&g, andDietaq Supplements
(HPS-820)
Centerfor FoodSafbtyaddAppliedNutrition
FoodandDrugAdministration
51OOPaintBranchParkway
CollegePark,MD, 20740-3835
Telephone
Numk (301)4362371
Dear Director:
In accordanceto the requirementsof Section 413(a)(2) (21 U.S.C. 350b) of the Federal
Food, Drug and Cosmetic Act, XxXx if filing for pre-marketing notice of new diq
ingredients in two Ayurvedic products (Asmakure and Pauekure):
The new dietary ingredients are:
Asmakure:
Abies Webbiana is a high altitude herb fmd in the Himalayaswith a very high anti-a&ma&
1)
property.
Adhatoda Vasica is a @uclitionallyproven herb to combatbronchial disorders.The principals of
2)
this plant are ahloids vasicine (mw 188, C 11H12N20),vasicinoneand vasicinol which are usedas
brochodialators.
Zingiber offiinale is a herb containingessentialoils like &giber&e and alpha-terpinone.These
3)
essentialoils havepotent auti-M
propertieswhich reducethe acutenessof bronchial infection.
Piper
longum
is
another
kind
of traditional herb whoseactive &redient, monocyclic
4)
sesquiterpencshascounterirritant and analgesicprop&es for reducingmuscularpain and Mamma&n.
Previousresearchhas found this to be effective in bronchial spasmand inflammation.
Piper nigrum is a medicinal herb which enhancesantibacterial function and increasesbio9
availability of other herbsnsed in the formulation.
Cinnamomum Zeylanicum is the herb having depressant
action on centralnervoussystem(CNS)
6)
and thus, reducesstressinducedasthma.
Ammomum subulabm is the herb which provides a soothingeffect on bronchop*hara@al
7)
region and hasa bronchosedativeaction.
Nisadal is a kind of white crystalline mineral substancewhich has mucolitic (i.e liquefying effect
8)
on dry cough) and expectorant(i.e expelsliquefied cough)properties.
Pyekure:
Hemidesmus Indicus L%nantamul) :&cent reseanhs have proved exclusively that the active
1)
principles of this plant consist of an enzyme, an essentialoil and a saponin. Rutin has been isolated from
leaves. Detectionof hexatriacontane,lupeol, its octa-cosanoate,mp. 8 lo, a - amyrin, p - amyrin, its acetate
and sitosterol in roots by chromamgraphy.
Ridnus Communis tSt&verenda) : castor oil consists of the glycerides of ricinoh5c,
2)
isoricinoleic, stearicand dihydroxy - stearic acids, Detection of palmitic (1.2), stearic(0.7), arachidic(0.3),
hexadecenoic(02), oleic (3.2), linoleic (3.4), hnolenic (OJ), ricinoleic (89.4%) and dihydro&aric acids as
Me-estersin castoroil was doneby GLC. The plant yields about 1% ricinine. Lupeol and 30 - norlupan3~-ol-2o-Onehavebeenisolated~thecoatofcastorbean.
Seedcoatcomainedl.SO-1.62%lipids
and higher amountsof phosphatidesand non sapomtiablematter than seedkernel.
Morhwa Ptervnosrwma tSaiiua1 : A reddish brown oil called ptergospermin with strong
3)
antibiotic activity has beenchemically isoW hm this plant. Aldotriouronic acid from acid hydrolysis of
gumhasbeencbatacterisedasO-(P-D-glucopyranosyhnoniccacid)(1~6)-B-D-galactopyranosyl
(1 3 6) - D - gala&ue. Presenceof aspartic acid, ghxtamic acid, glycine, threonine, alanine, w&e,
leucine, isoleucine,histidine, lysine, arginine, phenylalarine, tryptophan, cysteine and methionine have
‘( . .
been detectedin leaves. Alanine, arginine, glycine, tie,
&nine, valine, gh@mic and aspartic acids
have been detectedin flowers and iiuits; lysine in flowers, sucroseand gl~se in flowers and sucrosein
hits. 4-hydroxy-mellein,vanillin, octacosanoicacid, p - sitosteroland p - sitostenonehave been isolated
km stems.
Tinoswra Cordifolii tGulancha~ : Chemical analysis revealedthat the plant contained an
4)
&&id, glycosidesand sterol. An unidentifiedcompound,mp. 114“,an amorphouscompound,mp. 90”, a
physiologically active unidentified compound,mp. 119, a sterol, mp. 134“and a fatty acid, mp. 84’, have
been isolated f?om the plant. Al ditqenoid of columbin type - tinospoti (0.02%), mp. 184’ and
thmporide mp. 236”and cordifolide, mp. 176’havealso beenisolatedfrom the plant. Tinosporidineand f3
- sifosterol have beenisolatedfkom stems;and cordSol, heptauxano1and octacosanolm leaves. A new
fkranoid diterpene- tiuosporidehasbeenisolatedfrom stems.
Boerhaavia Diffusa (Rakta Punarnabal : Chemicalanalysisrevealsthe presenceof an alkaloid
5)
and an oily mass. Sulphates,chloridesand tracesof nitmtes and chloratesare obtainedl?om the ash. Ash
(11.8), Ca (1.2) and K 2.3%), presenceof alkaloids, ke and combinedamino acids have been determined
in aerial pmts of the plant. Boerhaavicacid, low tannins, phlobaphenes,reduchq sugars(glucose), and
0.01% of a crystalline basenamed punamavine were also isolad Hexa-triacontane,B - sitosterol and
msolic acid have been isolated fkom roots, a polysaccharidewas isolated which on hydrolysii yielded
glucose, xylose, glucuronic acid, galactose,L - avabinoseand L - rhamnose;a glycoprotein with a
molemlar weight of 16,000- 20,000daltonswas isolatedfrom roots.
All the relevant in vivo and clinical information is enclosed. These new dietary
ingredients will not be marketed in the US for 75 days after your expected receipt of this
Notice
Port orchard Nutraceuticals
/
1800 Sidney Ave l-203
Port Orchard, WA
98366
HERBiCURE PRNATE LIMITED
Metro Garden Cii,
Pailan, 24 PGS(S)
PANEKURETM
(A herbal research medicine)
Each Capsule Contents
:
Hemidesmus indicus
Recinus communis
Moringa pterygospenna
Tinospom cordifolia
Boerhaavia diffusa
Exepient (filler)
Indication
100 mg;
100 mg;
100 mg;
125 mg;
75 mg;
QS
:
Oesteoarthritis,
synositis.
pain,
inflammation,
ankylosis,
cervical
spondylosis,
arthralgia,
myalgia,
V
Panekure inhibits prostaglandians synthesis by COX2 inhibition.
2)
Panekure does not induced gastric or intestinal ulceration. Moreover, it promotes
secretion of cytoprotective mucus in the intestine and prevents mucosal damage.
3)
4)
Panekum has no damagingeffect on kidneys.
5)
Panekure is non-toxic and a very safe herbal medicine treatment by Panekure may be
safely continued for any length of time.
Dose :
1 - 2 capsule thrice a day or as directed by the physician.
Properties
1)
2)
3)
4)
5)
2)
3)
4)
5)
:
Hemidesmus indicus possesses a very good anti-inflammatory properties (Ref.1).
Ricinus communist has pain cure activity (Ref. 2).
Moringa pterygosperum is useful in fever and pain (Ref. 3).
Tinospora cordifolia is used as anti-inflammatory agents (Ref. 4).
Boerhaavia diffusa is useful in controlling pain and inflammation (Ref. 5).
References
1)
of Ingredients
:
Indigenous Drugs of India 2”d ed. 1982, Academic Publisers, p.188.
Ibid, p.236.
Ibid, p.364.
Ibid, p.426
Ibid, p-494
HERBICURE PRIVATE LIMITED
Factory: Metro Garden Ci,
Pailan, 24 PGS(S)
TOXICOLOGICAL DATA OF PANEKURE
IN S - D RATS IN P. 0. ROUTE FOR 6 WEEKS
Route P. 0. (Per OS1
For 6 Weeks
Parameters
SI.
No.
I
A.
1 Haematological
I
Test :
Normal
(Saline Control)
Tmated
(Panekure)
,
I
I
I
8.9 (7.2 - 9.8)
14.8 (12.0 - 17.5)
1240 (1100 - 1380)
8.6 (7.3 - 9.5)
14.7 (12.1 - 17.4)
1200 (1050 - 1240)
Cholesterol (mg/lOO ml blood)
127.5 f 2.0
120.5 f 1.9
(2)
Bilirubin Total (mg/lOO ml blood)
0.48 f 0.1
0.49 f 0.2
(3)
SGOT Unit/ml Serum
89.4 f 3.0
90.2 f 4.0
(4)
SGPT Unit/ml Serum
33.2 f 1.9
35.5 f 1.8
C.
Kidney Function Test :
(1)
(2)
Creatinine Clearance mUmin
Urea Clearance ml/min/m2
10.1 (6.3 - 15.2)
14.4 (3 - 28)
11.2 (7.5 - 16.0)
15.5 (4 - 291
(1)
(2)
(3)
Erythrocyte Value of Rat (million I dl)
Hemoglobin (gm I 100 ml)
Plateles : Thousands/d1 of blood
---
B.
Liver Function Test :
(1)
’ .
8
HERBICURE PRNATE LIMITED
Factory: Metro Garden City, Pailan, 24 PGS(S)
Effect of plant extract of PANEKURE,
Phenylbutatone & lndomethacin on the
hydwryproline content of carrageenin induced
granuloma tissue in rats.
Plant Extract
foorrgA<gMay
S.C.(PcO.01)
lndom@Mn Piwnybmm
5wwdY
S.C.(PeO.01)
IWmslKsMaY
8.C.(PcO.01)
.
I
8
H E R B K U R E P R IV A T EU M ITE D
Factory: M e tro G a r d e n City, P a i l a n , 2 4 P G S (S)
E ffect o f p l a n t extract o f P A N E K U R Eo t?
peroxide (glucose sxidase) i n d u c e d
inflam m a tio n .
70
60
50
G 40
c
.E
53
Lo
20
10
0
.
.
I
,
I
8
HERBICURE PRIVATE LIM ITED
Factory: Metro Garden City, Pailan, 24 PGS(S)
Effect
Mpirin
of plant extract of PANEKURE
and
(ref. standard)
on right hind paw of
adjuvant
induced
arthritis
rats.
2
1.8
1.8
1.4
Q, 1.2
5
91
3
m
r*
0.8
0.6
Piant Extract 80
m3$NoM&P.
< .
Aopirinloo
mM$Vojw,‘-~.
c .
I
l
,
.:,’
‘
.
8
H E R B I C U R EP R IV A T EU M ITE D
Factory: M e tro G a r d e n City, P a i l a n , 2 4 P G S (S)
A B R J E FO N A S M A K U R E
H e r b i c u r e ’s a n ti-asthmatic h e r b a l medicine, called A s m a k u r e , h a s b e e n d e v e l o p e d b y th e
D e p a r tm e n to fP h a r m a c e u ticalTechnology,J a d a v p u rUniversity a fter a p r o l o n g e da n d rigorous
R & D s p a n n i n gm o r e th a n 7 years. D u r i n g th e researchwork, very large b a s e o f pre-clinical
studies a n d p o s t-clinical observations w e r e carried o u t to reveal n o n - toxic e ffect o f th e
m e d i c i n ewith h i g h th e r a p e u ticv a l u e in asthmaticdisorder.
A collaborative e ffort b e t w e e n H e r b i c u r e a n d J a d a v p u rUniversity h a s b r o u g h t a n a m a z i n g
ayurvedicmedicine,called A s m a k u r e ,u n d e r In d i a n S c h o o lo f M e d i c i n e (EM), w h i c h a i m s a t
p e r m a n e nrelief
t
o f th e p a tie n tsfrom th e a g o n y o f asthma.
C o m p o s i tio n s :
A s far a s th e fo r m u l a tio n o f th e m e d i c i n e is c o n c e r n e dA, s m a k u r eis very different from th o s e
o f o th e r prevalent ayurvedic medicines. W h ile th e similarity generally fo u n d b e t w e e n
A s m a k u r e a n d th e o thers is only A d h a to d a Vasica, o th e r ingredients in A s m a k u r e a r e
c o m p l e telydifferent. A s m a k u r eis c o m p o s e do f e i g h t establishedh e r b s w h i c h all h a v e u n i q u e
e
m u l tid i m e n s i o n a l th e r a p e u ticvaluesa s follows :
1 . A b i e s W e b b i u n ais a h i g h altitude h e r b fo u n d in th e m o s t difficult terrains o f H i m a l a y a s
with a very h i g h a n ti-asthmatic property. H e r b i c u r e h a s p e r m a n e n ta r r a n g e m e n tfor
u n i n terruptedsupply o f this m o s t p o te n th e r b fio m Himalayas.
2 . A d h a to d u V u & a is traditionally p r o v e n h e r b to c o m b a t bronchial disorders. T h e
principals o f p l a n t a r e alkaloids vasicine ( m w 1 8 8 , Crr H r 2 Nzo), vasicinone a n d
vasicinol w h i c h a r e u s e d a s brochodialators.
3 . Zingiber o ~ c i n a fe is a h e r b c o n ta i n i n g e s s e n tial oils like zingiberine a n d a l p h a te r p i n o n e T. h e s ee s s e n tialoils h a v e p o te n ta n ti-bacterialpropertiesw h i c h r e d u c e th e
a c u te n e s so f bronchialinfection.
4 . P @ e rl o n g u m is a n o th e rkind o f traditional h e r b w h o s e active ingredient, monocyclic
sesquiterpenes
h a s c o u n ter irritant a n d a n a l g e s i cpropertiesfor r e d u c i n gm u s c u l a r p a i n
a n d inflammation. Thus, fo u n d in researchm o s t e ffective in bronchial s p a s m a n d
inflammation.
0’
5 . P iper n i g r u m is a m e d i c i n a lh e r b w h i c h e n h a n c e sa n ti-bacterialfu n c tio n a n d increases
bio-availabilityo f o th e r h e r b su s e d in th e fo r m u l a tio n .
1
’
.
8
6. Cinnamomum Zeyfunicum is the herb having depressant action on central nervous
system (CNS) and thus, reduces stress induced asthma.
7. A m m o m u m subulatum is the herb which provides soothing effect on broncho
pharangial region and has a broncho sedative action.
8. Nisadal is a kind of white crystalline m ineral substance which has mucolitic (i.e
lequifying effect on dry cough) and expectorant (i.e. expels lequified cough) properties.
Formulations
Research has revealed that most of the medicinal plants have a tendency to hydrolise in
presence of water which reduces the therapeutic efficacy. While some ayurvedic medicine is
formulated in syrup form (water base), Asmakure is formulated in dry-dry powder form
keeping moisture content less than 4% to avoid any possible hydrolysis and thus, to increase its
shelf life. Jn liquid base, synthetic preservative is generally used to avoid m icrobial growth and
all these synthetic preservatives are prone to toxicity leading to asthmatic attack. But in
Asmakure, there is no use of any preservative or synthetic additive and has been kept in natural
form .
Further, any pH shift can precipitate out some active ingredients from the syrup base, which is
ruled out in Asmakure for its dry-dry powder form .
Mode of Action of Asmakure vis-&vis other urevalent anti-asthmatic ayurvedic
medicines
Asthma is a chronic inflammatory disorder of airway. Mast Cells are releasing various
inflammatory mediators like prosta-glandins, leukotrienes, cytokine and histam ines. All are
broncho-constrictors and released due to disintegration of mast cell. While the prevalent herbal
medicines aim at only single mediator called leukotrienes, Asmakure covers ail mediators
which act as broncho-constrictors and it mainly performs as mast cell stabilizer and thus,
prevents the release of inflammatory mediators which lead to various kinds of asthmatic attack.
Asmakure, thus, has approached the root of the asthmatic disorder and aims at permanent
protection.
Apart from the above, Asmakure has a strong anti-bacterial mucolytic and expectorant action
and thus, offering a complete package of relief to asthmatic patients and even those suffering
from common cold and cough, and bronchitis.
Steu down auuroach
Asmakure has been designed in such a way so as to ensure assured result with sustained use of
the prescribed dosage which brings down even the steroid taking patients to the level of normal
breathing and tranquility. Regular use of Asmakure along with pure honey at least for a period
of six months also provides immunity to the asthmatic patients.
Clinical Trial
The clinical trial of Asmakure was carried out by the State Ayurvedic Medical College &
Hospital. The drug was administered orally among 32 patients (age between 12-55 years of
either sex, male 20 and female 12) for consecutive 28 days. The report concludes “clinical
results revealed that most of the patients who were su#ering jkom bronchial asthma, and
chronic dry cough, got reIief from asthma complications due to Ayurvedic drug, Talishadiherbi (Asmakure). The patients ’compliance of the drug was satisfactory and it can be strongly
recommended that the drug can be very use&l in asthmatic management. ”
Patent of Asmakure
Keeping in view the inventions made towards the process management of the various extracts
of active ingredients of the herbs used in the formulation of Asmakure and the exclusivity of
Abbies Webbiana, in particular, Herbicure has applied for domestic as well as international
patent of the product.
**************************************
HERBICURE PRIVATE LIMITED
Factmy: Metro Garden Cii, Pailan, 24 PGS(S)
ASMAKURE
Annexure
-I
PRODUCT DATA SHEET
Presentation
Dry-Dry Powder in 100gm bottle.
Uses- Effective against allergic Bronchitis and Asthma. Also brings relief in common
cold and persistent cough.
Doses- l-2 tsf twice daily.
Administration-
Administration through P.O. along with honey.
Contra-indication
: Nil
Use in pregnancy and lactation: Not yet established.
Sideeffects:‘No
known side effect.
Precaution: Sudden withdrawal of any existing medication (anti asthmatic) is advised
against.
Warning: Not found.
Absorption:
Good.
Fate: Metabolism, partly through first by pass.
Distribution:
Apparent volume distribution (vd) is moderate.
Metabolism:
Mainly by liver cells.
Excretion:
Elimination:
Entrance excretion through high pH (alkaline) urine.
Related with urinal pH.
Package Quantity: 60 bottles (each of 100 gm) in a single carton.
HERBICURE PRIVATE LIMITED
Factoty: Metro Garden City, Paibn, 24 PGS(S)
ASMAKURE
Annexure
- II
TECHNICAL DATA
a)
Acute test (single dose). Test in which single doses of the drug are used on each
animal on one occasion only for determination of LDSOor Median Lethal Dose (MLD),
i.e. the dose which will kill 50% of the animals of a particular species. Lbvalue is
determined in a 24 hour test using two species (mice or rats) and one non rodent
(usually rabbits).
Acute toxicity studies of ASMAKURE in animals studies revealed:
0
Even a very high dose in animal by p.o. route did not produce any mortality in
rats and or rabbits. So, there is no question of LDSOvalue determination.
Behavioral patterns (like motor activity, CNs stimula dep.) were also
unaffected due to Asmakure.
Subacute test (daily dose): Tests in which animals (usually rats) are given dose daily starting
at around expected therapeutic level and increasing stepwise every two to three days until
toxic signs are observed. Hematological and biochemical monitoring are carried out. After 24 weeks pathological and histological examination are dose after killings the animals.
Subacute toxicitv studies of ASMAKURE in rats for 4 weeks revealed:
1)
Dose in oral route (P.O.) was well tolerated by the animals for continuous 4
weeks treatment.
2)
There were no haematological abnormalities in animal due to ASMAKURE
treatment. Hb, WBC, RBC were unchanged and there was no depression of
bone marrow due to the herbal medicines.
3)
Liver function tests were also unaltered due to Asmakure SGOT SGPT.
Bilirubin level of treated rats were within limit after subacute treatment with
Asmakure. Histological findings confirmed about unaltered liver cells
architecture.
4
Mutagenicity studies revealed that the herbal drug ASMAKURE
any mutagenic effect.
cl
If the drug is to be used in women of child- bearing age, its effect on fertility as well
as its teratogenic potential must be investigated. Asmakute was tested on pregnant
rats extensively for conformation of its safety in women of child-bearing age.
However, we have not performed the clinical test on human subject to find say the
drugs safety in pregnancy.
d)
Other find toxicological .studies, like kidney function tests also confirm the drug’s
safety.
is totally free from
HERBICURE PRIVATE LIMITED
Factory: Metro Garden City, Pailan, 24 FGS(S)
ASMAKURE
Annexure
- III
PHARMACOLOGICAL
1)
DATA
Human Phamracokinetic and metabolism.
a)
The drug is acidic in nature. So its ionization in gastric pH is less (low pk
value). The drugs absorption of gastric region is very high.
b)
Oral absorption is very good and bio availability is also good.
cl
Apparent volume distribution0/d) is moderate.
d)
Half life(t l/4) : 10-12 hrs.
e)
Biotransformation: Through hepatic enzyme.
9
Heptic/renal failure: Dose should be adjusted in hepatic or renal failure
patients.
9)
Au: Elimination of drug in alkaline urine (high pH) is high.
2)
Studies mainly done on mast cell stabilization and bronchodilatation activity in animal
to establish the drug’s anti-asthmatic value.
3)
Secondary pharmacological action like mucolytic and expectoration action of the
drug has confirmed its action as mucolytic expectorant.
4)
Drug Interaction Studies: There was no such drug interactions found with modem
antiasthmatic drugs.
HERBICURE PRNATE LIMITED
Factory: Metro Garden City, Pailan, 24 PGS(S)
ASMAKURE
ANNEXURE- IV
TECHNOLOGICALDATA - ‘A’
COMPOSITIONFORMULAOF ASMAKURE
SY
w.,,
I
INGREDIANTS
___-__---
-_--
-
I
% COMPOSITION
1
ABIES WEBBIANA(TALISHPATRA)
2.11
2
ADHA TODA VASICA (VASAK)
10.30
3
CINNAMOMUMZEYLANICUM(DARUCHINI)
1.00
4
AMMOMUMSUBUlATUM (BARA ELAICHI)
1.00
5
PIPER NIGRUM(GOLMORICH)
4.07
6
PIPER LONGUM(PIPUL)
8.25
7
ZINGIBEROFFICINABLE(ADA)
6.27
8
NISADAL
1.00
9
SUGAR
68.00
6
HERBICURE PRIVATE LIMITED
Factory:
Metro Garden Cii,
Pailan,
24 PGS(S)
ASMAKURE
ANNEXURE- IV
TECHNOLOGICALDATA - ‘B’
MANUFACTURINGINSTRUCTIONSFOR ASMAKURE PRODUCTION
RAW MATERIALS
WEIGHINGOF
’ EXTRACT& HERBAL
POWDER
GRINDINGOF
MISHRI& HERBS
-+
WEIGHING d&&-~~~
SHRINKING
--•
T
QUALlTYCHECK
HERBICURE PRIVATE LIMITED
Factory : Metro Garden Cii,
Pailan, 24 PGS(S)
ASMAKURE
ANNEXURE- N
TECHNOLOGICALDATA - ‘C’
CONTROLDATA FORTHE ACTNE CONSTITUENTS
OF ASMAKURE
ACTlVE CONSTITUENTS
Sl#
REMARKS
ALKALOIDS
01
VASICINE
PIPERINE
PIPERLONGUMINE
PIPERLONGUMININE
iv)
VOLATILEOILS
i)
PRESENTWITHINLIMIT
ii)
iii)
02
0
ii)
EUGENOL
CINEOLEZINGIBEROLE
PRESENTWITHINLIMIT
03
ESSENTIALOILS
PRESENTWITHINLIMlT
04
TERPENES
PRESENTWITHINLIMIT
HERBICURE PRIVATE LIMITED
Factory
: Metro Garden City, Pailan, 24 PGS(S)
ASMAKURE
ANNEXURE-IV
TECHNOLOGICALDATA - ‘D’
CONTROLDATA FORFINISHEDPRODUCT/ASMAKURE)
TOTALWEIGHTOF THE SAMPLE
01
NLT 100GM.
02
MESH iKE
99% THROUGH20 #
03
SOLUBlLllY ( IN WATER)
NLT69%
pH OF ASMAKURESOLUTION
10% (W/v) SOLUTIONIN WATER
20% (W/V) SOLUTIONIN WATER
30% (IV/V-)SOLUTIONIN WATER
1% (W/V) SOLUTIONIN WATER
4.0 TO 4.0
4.0 TO 4.8
4.0 TO 4.8
4.0 TO 6.0
05
MICROBIALCOUNT
10000CFUIGM.
06
TEXI-URE
COARSEPOWDER
07
COLOUR
LIGHT BROWN
08
TASTE
SWEETISH,PUNGENT,HEATING
09
ODOUR
SWEET PUNGENT
10
L.O.D.(%W/W AT 105oC)
NMT5%
11
BULK DENSlTY
NLT 0.75GMIC.C.
12
REFERENCE
AYURVEDlCPHARMACOPEIAAiD
INDIAN PHARMACOPEIA
04
i)
ii)
iii)
iv)
HERBKURE PRIVATE LIMITED
Factory : Metro Garden City, Pailan, 24 PGSfS)
ASMAKURE
ANNEXURE- IV
TECHNOLOGICALDATA - ‘E’
STABILITYDATA AND PROPOSEDSHELF-LIFEOF FINISHEDPRODUCT(ASMAKURE)
THE STABILITYSTUDIESOF THE DRUG WAS CARRIEDOUTAT THE THREETEMPERATURESNAMELY
37oC,40% & 50% AND IT WAS FOUNDTO BE STABLE.
THE SHELFLIFEOF THE DRUGHAS BEEN PROPOSEDTO BE THREEYEARSFROMTHE DATEOF
MANUFACTURING
AS MENTIONEDIN THE LABEL.
HERBICURE PRIVATE LIMITED
Factory : Metro Garden City, Pailan, 24 PGS(S)
ASMAKURE
Annexure
-V
CLINICAL DATA **
(Reference
a)
No.JBR/PS-1 g/2001 Dt: 19/02/2001)
Phase I Clinical Trial ReDort :
The drug (Asmakure) was administered orally to a number of patients(Age between 12-55
years of either sex, male 20, female 12) who were suffering from asthma, in the done range
of l-2 teaspoonful twice daily (B.D.) with honey for 28 days consecutively day.
Clinical trial revealed that, most of the patients who were suffering from bronchial asthma,
and chronic dry cough (non productive cough) got relief from asthma complication due to
this Ayurvedic drug. In most of the cases, it has been found that the drug has a definite
expectorant action.
The patients compliance of the drug was satisfactory and it can be strongly recommended
that Asmakure can be very useful in asthma management.
W
Phase II Clinical trial :
Not done.
cl
No side effect /adverse reactions was found in human subject who received the drug
for 28 days consecutively.
d)
Report on clinical and pharmacological studies are in process for publication.
Name 8 Address of the lnvestinator
:
Dr. Gopal Chandra Sengupta
Principal - Superintendent
J. B. Roy State Ayurvedic Medical College & Hospital
Kolkata, West Bengal
l *
As per recent guidelines of WHO, the Ayurvedic medicines require less stringent Clinical Trials
to go throughsince these medicines are based on time-tested traditional practice spread over a
long periodof time.
I
’
.
.
0
.
0
.
HERBICURE PRIVATE LIM ITED
Factory: Metro Garden City, Pailan, 24 PGS(S)
Table-l
Effectof
AsnmakweondShrentsymptosmsands’tgarofAsthma
Present before
5.
Ronchi
6.
Difficultyof expectoration
After treatment
8110
40150
am
6150
3150
0150
au0
30150
0150
0150
O/50
0150
Table41
Svrirometm
Studv
Retort
of Asmakwe
Treatment
Asmakure Treated Group
.
,
* .
0
HERBICURE PRIVATE LIMITED
Factory: Metro Garden City, Pailan, 24 PGS(S)
Table-Ill
EffectoiAsnma
kure on Respirators
Rate of Asthma
Patients
Treatment with Asmakure
4'hweek
2"Week
Treatment with placebo
V Week
8thweek
25.0 f 1.9
21.07**1.2
18.72**0.01
18.52*iO.O2
17.97*f 0.05
P values
< 0.05
c 0.001
< 0.05
c 0.001
Table-IV,
Treatment with placebo
1”Week
Treatment with Asmakure
4thweek
2dWeek
1230~10.50
1570 *9.3
1680~~11.5
Pvalues
< 0.001
< 0.001
8thweek
1930i13.2
2100 *7.3
< 0.001
< 0.001
HERBICURE PRNATE LIMITED
Factory: Metro Garden Cii, Pailan, 24 PGS(S)
PrickTest
(SkhTestingwithdiEkemtAUe!rgens
tothePatietrtr~edAsmakure]
Treatmentwith Asmakure
Cat (furs)
+I-
+I-
Rabbit(furs) -.
*
+t
+
Ship wool
(fabric)
+k
-4-t
+
@N
+t
+
Milk
+
+
+
Grass (pollen)
+I-
+I-
+
Cheese
++
++
-
a
c
0
:’
.
.
. -
.
.
HERBKURE PRlVATE LIMITED
Factory: Metro GardenCity, Pailan,24 PGS(S)
Table-W
BiochemicaJ Chanws to the Patients who
received Asmakure for 8 Weeks Contluuoud~
Parameters
Treatmentwith placebo
(No. of Patients 10)
Treatmentwith Asmakure
(No. of Patients 30)
Haemogbbin
12 AZ4 gm/dl.*
13 * 2 gm/dl.*
Red cell count
4.3 f 0.1x 10s/ ur
4.5 f 0.2x 1061ur
MCHC
30 + 9 % ”
33 f 8%*
Eosinophil
13 f 0.1%
6 * 0.010/6""
ESR
22 f 1 m m lhr.
20 f 2 mnVhr.
Glucosetolerance
175 f 5 mg/lOOm l
175 f 7 mg/lOOm l+’
0.1 A 0.2 mg/dl.
0.1 f 3 mg/dl.*
6.0 i 1 gm/dl.
6.1 f 9 gm/dl.*
14 f 4 units/ml.
12 f 3 units/ml.*
20 f 4 units/ml
19 * 8 units/ml.
80 f 8 umolA
78 f 4 umolA
40 f 7 umol/l
38 f 4 umol/l*
Hematolo&al
Liver Function Test
Bilinrbin(Total)
Protein(Total)
SGOT
SGPT
Kidney Function Test
Creafnine
Creatine