Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
2 1 4 1 1 2 6
CO~B~q~ DR~
F0R q!~T~ ~.
PI OF ~B ~rI
Thisl invention relates to aompo~itions and metho~
u6eflll in 'chs treatment of migraine h~ches and re3~ated
il1n~ 6.
1121D QF ~ r~TIo~
Ths ~ncidenc~ of migraine including clufft~r ~ ch~s,
i~ 6aid to ~e ~y~LOXi~ately lo-ao~ of the male population
an~ Z 0-3 OS of t~e femal~ population. Trsa~ment ~or ~any
pati~nt~ havi~ the occaffional migrain~ involve~ 3imp~e
analgesics ~ith or without s~dative~. approximately 10~ of
~igraine 6u~fer~r6 hav~ three or more attacks per month and
warrant prophylactic treatment. ~wenty-five to ~i~t~
.
.
-`- 2141126
,
percent o~ thl~ group benef~t ~r~m treatment w~th beta-
adr~nor~cept~r ~locking agent~, cl~nidine or, in the femal~
s~f~erer, ge~tag~n hormonQs. In the re~aining population
of migra~ne ~uff~rer~, and ~ n tho~e with intolerable s~de-
s~fectg from availabl~ drug~, th~re i~ a laoX of
con~elll ional pharmaceutiaal prep~rat~on~ that sxhibit
therap~tic Qffsct, wit~out ~svere ~ide-Qff~ct6.
F~v~rf~w, rich in ~e~quitel~c.le lactone~, principally
parthenolide, hag algo besn ~hown to hav~ a prophylactic
effsct again~t-migraine. ~n one ~tu~y, mors than ~0~ of
the fevsrfew Users cla~ed that the herb haa d~cr~a~e~ the
frequency of.thelr att~ck~, cauesd th~m to be l~ pain~ul,
or -~oth. In another 8tu~y, ~xt~-eight p~C~L of ~igrainQ
~Uf~t-~l~ d~played ~m~lO~Qment when tr~ated
y~ ylac~;c~l~y wlth riboflavin.
Al~h th~ ~ ~ cau~ or ~ of ~igrain~
arthrl~is, an~ a~ r~a~n ~ , all three ~ ee
- are a~c;~t4d wi~h a :postulatQ~ local or gy~temic relea8e
of active ~uL c~ o ;~l--A~ n t~e ca~e Of mi~raine
and/or it~ variant~: ..w~ ephrins (--vra~ n~l ;ne), ~-
h~d~ L~y~mine (~erotonLn~, histam~ne, ~ p51~n~na
and ~l~dy~;n~n; ~n the ca~e of arthr~is~ pro8tagt~ n~,
higtam~ns, 5 ~L~L~ am$ne ana brady~1~;n; and in t~e
ca~;e of a~thma; his~mine, 5 l~J~ yL~ ne~ brady~n;r~
25 acetylcboline, ~G~I,J~3~ n~ ~nd the leukotrien~s.
endo.~ ~-o~ t7 hav~ in- co..,. ,on t~ h; 1 Sty to cau~e
~mooth m~scle to cc ~ act ti.~. go into ~epa~m~, and ~a~y
- are also pai~ n~ ~ubst~r~Ge~, e . g . S--
hydroxytryptamine, braClykinin, histamlne and
30 pro~:taglAnA~ . Non--sQ3.eCt$ve an~:agoniC t drugs wil~,
ther~for~, not only reduc:s t~ ~mooth muscular spasm (o~
. .int:rscranial blood ~e~;s~ls in t;h~ case o~ migra~n~, or
bron~h~ moot:h muscle in the ca~e of asthma~ ~ut a}~o th~
pain (o~ ~igraine and arthr~ti~ a~ociat~d w~t~ their
35 r~lease.
2 1 4 1 1 2
8esquiterpene lac~on~s ar~ known to b~ pre~ent in many
pl~nt~, for exampl~ ~n A5ter~c~a, Nagnol~ac~ae, and in
particular in Tan~c~tum parthen~um (f~ver~ew~, an~ are
thought to b~ re~pon5ible for ob~rved bioactivity of the
leaf mater~ al .
su~A~Y OF TH~ I~V~IO~
It ha~ no~ been di&oo~c ~ that a mixt~Q o~ a
~esqu~t~rpen~ lactone and a B-vi~am$n, is esp~c~ally
effeGtive in both the ~e~Lm~nt an~ prophylaxis of
10 migraine, arthrit:i~, and a2~ ~ a~
In aocordanqe with the y~. ~nt invent$on, a
se-quiterp~ne lacton~a, or a 2~0~ ~ of se~
l~ctone~, s~lch as se~ait~.e, laa~ .a c~ n~n~ plant~
asld ~lant ex~r'aats, i~ u~ed in cc~ n~tion W~th a B-compl~x
16 ~ita~in, Bt~h as ribofla~rin. i ~a~ lo~ ~mpriging eeuGh
a coD~bination are al~o pro~rided that: hav~ ~har~aceut1 cal
u~e, par~ ly in the tr~atment oi~ ~gra~ne, inc~udin~
ClU8t~ hq~r~ an~ variou~ rit~ c and ~LO-
~
condition~, OEUtih ag a~thma~
~ ~ D~8C~r:~l ~ ~S ~1~ ~3~1!1!~
q~e 8-complex vit~n t~at i~ u~eful in accorClanos
with t~e ~ ~ t i~vent~on includ~6 riboflavin, r~boflavin
-te, flavin ~ n~ ~n ~n1sotia~ niootin~c aciCl-,
folic aaid, cy2~ ha l~in, para-amino benzoic acid~
25 thia~ns, pyr~ , panto'rh-n;~, aci~, ~iot1n, choline
inos$tol, and carn~tine.
The ~e~qUitsrpQne lacton~ that i~ u~eful in aac~rdance
with the ~~ ~t inv~ntion include~ ~ ~cranolid~,
~ A~lid~, and ~ ~lidQS, in particular tho~e
se6qUiterpQne lac~one~ having an ~-m~thyl~ne &ub~tituent in
the la~ton~ ring, ~uch a~ parthenolide. ParthQnolide and
squiterpene lacton~-con~n~ plant material~, ~uch a~
~verf~w l~a* or extract~ fro~ such plant mat~rial~ are
. prQferred
. .
~1~1126
Although bath ~e~qUit~rp~nQ la~ones and 8-complex
vitA ~ n~ have bee~ found, individUally, to be effect~ve for
treatm~nt or prophylaxis of migraine, ~he combination ~f
the two typ~ of active~, in accordance with the pre~ent
~nv~ntion, leads to eyn~rgist~c ef~cts. Thus, a
combinat~on o~ f~ver~w or other ~ourc~ o parthenolids
with a B-vitamin additiv~ lead~ to a further d~crease in
the frQquency of ~h~ attacks an~ cau~e~ the attacks to b~
l~g painful. An inCreasQd perc~nta~Q o~ m~graine
sufer~rs ~hould thQrefore d$splay an improvement in
frQquency~ sQVerity~ or bo~h, wh~n treated prophylactically
with th~ comb$national ~rug. ThQ co~b$national drug ~a~
low to~ty, ~ty~ i~ingly few ~id~-e$f~cta an~ may be
ta~en for ~he ext~ fl p~riod~ required for effsct~ve
15 ~ o~h~l~xis, w~ thout ~ e re;~c~ion~ .
~OP~ ~-~ ANn Pua~t~ T~ ~p~D-~T~a~ N
The ~c -~o of ~ctivo ingredients w~ll, of couree, vary
fra3l~ indlYid~lal to ind~vid~lal an~ will ~E!~n~ upon many
~a~or~, inal~ boa~ ~reight, nleta~1 i~m, and 1:he lilce.
In general, ho~rer~ t i6 believea that, in l~o'ch treat~ent
and ~-~pl~laxi6, a giVen indlvi~ual ~ 1~ receive ~rom
abo~t S0 to about lO,O00 mi~r~y~ms, preferably ~rom about
250 to a~out loOO ~ic~vy ~ms, and ~ost p~ferably a~out 250
~i~r~.~ms o~ eesquiL~cne lactone, ~u~h a8 F~r~henolide,
per d~y. ~n general, it ia a~o believed that a gi~en
individua~ ehould rece~ve fro~ about 0.1 to about 5,000
gram~, preferably from about 100 to about 500
~illlgram~, an~ modt preferably about 400 ;ll~gr~m~ of B-
co~plQx vitamin, s ~ t~lly r~hnflAvin, per day. More,
hc~ , may ~e need in the case of aCut~ attack~.
Th~lS, in accordanc~ with th~ prssent inv~ntion,
phar~ac~utical do8sge ~orms ars prov~ l that conta~ n
50 to about lO,OoO mi~o.J~ , preferaPly ~rom abou~ 250 to
about lO00 m~ -;r 0~L , an~ mo~ preferably a~o~lt 250
mi~ o~ se~iterpene lacton~, ~u~h as par~henol ~ de,
2141126
in combinat~on with abaut 0.1 to about 5,000 milligram~,
- pre~rably from about 100 to about 500 milligram~, ~nd mo~t
pr~erably about 400 m~lligrams of B-compl~x ~ltamin,
e~pec~ally r~boflav~n, p~r day.
In gener~l, ~uch pha~aCeut~cal do~age ~o~ms ~ay
compr~e from about 5 to 300 mg, e~pQcially 50 to 200 mg,
of f~verfs~ lea~, contA;n~ng a~out 250 m~crogl~ of
parthenolidQ, in com}~ination with from al~out 0.1 to 400 mg
o~ riboflav~n per day. For treat~ent, mors than onQ dose
~ay be required, as in thQ casQ of the treatment of an
acut~ ~ttacX of m~graine or a~liQd di~ord~r. Th~ fever$ew
~ ~ may ~e adjusted to ~ccommodat~ thQ nat~urally
vari~le level~ of ~Qs~uiteL~-e lactone~, s~ch a~
parthen~lide. A par~ ~ly pr~f~rred c~p~ e contain~
16. abaut 125 mg o~ hiy~ pa.lh~nol;~e fsverf~ and 400 mg of
r~boflavin. 'It ~S prQferrea that thQ c~mpo8ition o~ the
nt inv~ntion be aomini~ersd as t~o tablst~ daily;
~a~h tablet cont~ ng 125 mg fs~erf~W (cont~in;~ 250 mq
o~ ~sqult~ ~.~ - lactone) an~ 200 mg r~boflav~n or oth~r B-
GomplsY vitamin.
For thQ L ~ment or p~ lax~s o~ m~graine the
~ a~$ona may be admini~t*red orally, or ~ erallyand ~ ~.i~ntly take t~e form of a tablet, ~r~ ~t,
c~r~t~le~ 1~7-~, in~ectable solution, liguid ~uspensi~n or
~ ~. Circum~ r~ may ari~e wh~rein the dos~ i~ best
a~in~stsr~ by ~ c-itory, in~7~tion, slow releas~
$~p1ant, ~l~w ~slea~e patch or oth~r topical ~hi ~1~.
~ he combination of active ~ngredients are usually ~e9t
gi~en ~n an or~l form ma~e up as a tablet, caplet, capsule,
or a6 a 1 ~ quid su~pen~i on or ~1~Y; r on~ or two timQS daily.
For oral adm~ni~trat~on, the pr8para~ion may bs adm~xe~
wi~h any ~onventio~al ta~l~t~ng or ~r~ ing carrier, ~r a&
a ~-=p4l~ion ~r ~olut~on ~n-any orally accspta~le non-
toXic li~uid carrier. If ds6ired, the drug may be prov~de~
in ~noap~ula~s~ form ~or ~u~t~e~ rel~ase over a period of
time. For paren~eral a~n~tra~lon th~ drug ~ay be
21~1126
provide~ as a ~u~pens ion or sol~ltion in any ~uitable,
~terile injeation medium, e.g. sterile aqueous ~3aline
olution. Giv~n thQ de~3~red doage rates indicated above,
~ he appropriat~ method of formulat~ on of the drug in a f~orm
5 suitabl~ for oral or parenteral admini~;trat:ion will be
obv~ou~ to psr~on~ ~killed in th8 art. Th~ ~amQ appl~ e~
for ~nh~l~t~ and rectal or ~low - rQlea~Q implant mod~s of
administration, which ar~ aleo feasibl~.
~he p~arm~ceut~cal formulstlons may ad~iti~nally
$n~1ude, in add~tion to the aforemention~d active agent~,
OthOE known anti-migrain~ pr~parat$on , analge~ics and
anti~meticg OEuch ae:
L tC~ 0101 h~ Q~iCle
Ergo~am~ne tartrat~
~ethysergi~e ~alea~e
Dil,yo~- t~amine ~Q4yiate
8 ~,y~O. h~id8
Iso~et~spten~ Mucate
~ in~ Dih~ok~ id~
Metoclopra~ds ~,dk~ e
Pizot$fen h~d~o~en ~alat~
A6pirin an~ other non-steroldal anti-in~lam~o
agent~
Wh4 ~e willow ~ark and its extrac~
Oth~r ~-v~ sro~dal anti-infla~matoxy agent~ of plant
orig4n
Paracstamol and other minor analq~c~
P~n~:azoc~ns ~ O-~hl ~rid8
ProchlG~ ~dzins
CaffelnQ
Me~GL~. -te
E~h~rta~ ~ ne Citrate
Zomsp4rac
Mepta~inol IIyJl~chlori
DEH
sumatr~ptin
21~112~
Ging~r
Brazilian Coc~a
Excellent ~fficacy o~ a pr~paration in accordance w~th
thi~ inv~ntion ~s lik~ly in ~11 form~ o~ migra~ne including
the trcatment of cla~ical and common migra~n~, m~grainous
n~uralgla (clust~r heA~-~h~), an~ premen~rual and
m~n~trual migra~n~ and ot~er h~-che6~
m e ~ ro~tion~ o~ the ~r~ n~ inven~ion ~ay bs used
in tbe ~evd~Lion ~f th~ a~orement;Qne~ ~y~- - of h~che
by r~J--~ln~ the frequency, severity and duration of the
at~adk~ and.by ,c~ n~ th~ ~sa and ~omitin~ ~ymptom~.
Th~ composition~ ~ay also be u~ed to trs~t acute attaok~ of
the afor~mentio~ed types of ~ æ~ y reA~G~ng the~r
dl-ation~ qeverity and ~h~ intensity of ~r-i~ted
eymptom~.
For the trea~me~t of arthritic con~ition6,
-eyd~aLion~ ln accoroance w~th the in~ention may be
ad~nietered orally, or parenterally and ~.v~.iently tak~
the form of ~ tablet, cap~ule, in~e,~abl~, ligu~d
6ucF~e~on or ~1~Y~, circuL~ , may ar$ee ~her~ it i~
b~St adm$n~elel ~y ~a~ nb-l~t~on, slow r~
~rl~n~ 81q~ r~l~ patch, or oth~r top~cal vehicle.
-DoRage and admin;~tration ~ a~ ;~te~ a~o~e.
A ~ a~ on in accordance with th~ inven~ion may
addi~n~11y ~n~~ e other an~ Lh.iti6 agQnt~ $ncluding-
I.C - ~ t~o$~al anti-inlammatory drugs, ~n~l~J~ icg, skeletal
mu~cle re~ ~ts, steroids, gol~ an~ pen~c~llam~n~.
Exa~pl~ of ~uch agents ar~;
a~p~rin,
indomethacin,
p~roxic~m,
bQnorylat~,
~b~profen,
parac~tamol,
21~1~26
-
~_ 8
~alicylam~ne,
di~lunlzal,
ethoh~ptazine,
fenoprof~n ~calci~m ~enoprofate~
~luf~namic acid,
mefenamic acid,
naprox~n ~od~um,
k~toprofen,
phenylbut~zone,
~ulindac,
p~ni~ f ~
sallcylate,
fenclofenaa~
flurbipro~n,
1 5 fenb/u~en,
fQp~a~one~ -
~odium aurothiomalate,
nay 0~
~O~ Oren,
AlO~lr~ia,
l~d~o~y~Lloroq~ine st~l~h~te,
- az~ ~7qn~,
~ol~mtin~
cho}ine m~ ltF ~ l~m tr~ d~ l i aylate,
diclofQnac~
adrenal steroi~ ~UCh as pre~ r~n~ or
~ qA~ one~
white willo~ax~ and itS extract~,
other ~on ~LQro~ dal anti-in~lammatory ag~nt~ of
plant origin
~vening primrOse oil
gamma linole~a aci~
bor~ge oil
~l~x seed
21~1126
~_ g
Th~ compo~it~on~ of the present invention may be used
in the treatm~nt of rheumato~d ar~hrit~s, ost~oarthriti~,
arthriti~ a~sociated with Felty'~ syndrome, 5till~s
di~Qase, ~ystemia lupu5 erythemato~u~, polyarter~tis
nodosa, sclero~erma, gout, achalasia of ~he cardia, Crohn~
disQa~e, chronlc ~ruc~llo~is, ankylo~ng spondyliti~,
~arcoidosi~, psoria~is an~ gonorrhoea.
The preparatione are ~el~eved to be useful ~n the
~v~J,Lion o~ ths above arthr~tids~, betng effective in
reducing ths freq~ncy, 6ever~ty and durstion of the
~X ~oms The preparations can ~lgo be u~ to treat the
acut~ attack~ of th~ above arthritides r~At~a~ n~ th~r
~uration, ~ ity ana a~ t~d ~ymptom8.
It is alao bellevsd that th~ e~f icacy Of She
1~ compositiong o~ the y~ t in~ntion c~n be ~nh~n~QA by
the ~ of gamma ~ c aa~. Thu~, the
compasitions way compr~6e, in add~tion to a se~g~t~
lactons and a B-co~plsx ~itamin, gamma linol~c acid or a
~ur~ th~a~L. The l~n~ts;~ ac~ -~u~e m~y b~, for
exa~p~e, evening pri~ross oll or Lor~y~ oil.
For th~ tr~atm~nt o4 ast~ma~ ~l ~L~L~ an~ in
accordan~e wi~ th~ in~ntion ~ay be aaministersd orally,
-or ~a~ erally and ~A~,~.i~ntly take-the form o~ a ~abl~t,
~p~tl~, in~ A~l~, liquid ~~ -a~on or
~irc~m~ -c~-- may ari8a where $t is ~e~t a~ni~tsred by
Y~ 'o~;tory~ ~nh~l~tion~ 810w rel~ass implan~, ~low r~leass
patch or other ~opical ~hicl~. Do6age and administrat$on-
are a~ ind$catsd above.
A preparation in accor~anc~ ~ith ths invent$on may bs
30 co - a~ ter~d ~ith o~ addi~A 1 1 y lnclu~e oth~r
ingr~i~nts ~uch as ~o--~hod~lator, antihistamine an~ anti-
~nf~ctivs agent~, ~xample~ o~ which ag~nt~ are:
i~opr~ n~ sulphate,
orcipr~n~l~ne,
adr~n~l~r~,
ter~u~aline ~-11rh~
- -
- 2~112~
theophyllin~,
brazil~an cocoa
choline th~Qphyllina~Q,
aminophyll~ne,
~rhQ~rin~ hydrochloride,
papaverin~ hydr~chloride,
ipratropium ~L~
atropinQ methonitratQ,
b~cl ~ ~n~On~ dipropionate,
fenot~rol ~r~L ~m~d~,
be~ t~,
ieoetharine me~ylate or hy~v~.lorid~,
phenyl~phrin~ ~dhG~ de or bitartrate,
thenyidia~ne hy~ ~id~,
-~p~o~ol ~k ~hlQ~i~e,
de ~ opin~ citrate,
bu~etha~ate cl~rate,
pify~ n~
diphenylpyraline L~3r~hlQr~e,
~ ~ cromoglycate,
-etaE$phylllne camsylat~,
in~ ~ r~ ~la~ine,
etaredrine h~d~l.lorid~,
bufylline,
g~ el ~.,.. ; n,
~d~ a~amlnQ h~ de and o~her hi~
Hl~ ~. anta~oni~t6,
dly~l.~ll5.ne,
mcU.~X~ na~in~ 1,~l~o~l-loride,
rimitQr~l hydrobro~ide,
- hyo~n~ hydrobromid~,
~albut~ol ~ulphate,
ketotifen hy~L~I fumarate,
~S~ ~rh9~rine hy~Lo~lloride,
3~ ne hy~rochlorid~, and
antifungal, ant~bacterial and antiviral agents
2141126
-
1 1
Th~ comp~sition in accordana~3 with th~ pre~ent
invention i~; ~elieved to be useful in the ~r~atmen~ of
bronchial a~thma, 3~ronchocon~ ction a~sociate~l with
chronic bronchiti~, and ~ymptom~; asso~iated ~ th hist~rl nQ
5 release in all~rgic hyper~snsiti~rity ph~nomena such a6 hay
fever and anaphylaxis.
~ __ ition~3 in accordance with th~ invention will
now bQ illus'crat~ in more d~tail with refeL~-~:e to the
~ollo~ing Exan~ple:
~XP~E 1
on o~ r~ 5
F~w~e ~ feverfew ~ and riboflavin are mixed in ths
~ollowing ~, ~.po~ Lions:
~ æt~nd~~ Qverfew lea~ rd~r
tcon~ ; n~ at leaet ~.29~ LLcnol~de) 125 mg
ribofla~in 400 mg
~he mixturs 1~ ~.c~ l atea into a ~o~t shell ca,~ e or
ha~d ~hell ¢~p~-l~ or two pie¢e hard shell gelatin
c~r~ . The c~ may be treat~d to r~tard
~ie~ntegratlon ar ab~orption by th~ u~e of ga~LLo r~_istant
caatlnge, ~uch a~ dLo~m~thyl propy} c~ll~lo-^, or th~
- contsnt may ~ mixsd w~th polymer~c matr~x materials a~
those known to the pharmaeeutical indus~ry, to r~l~e~ the
ac~ivQ ingr~ient6 ~t a ~l~r~lled rate. The soft shell or
t~o piece har~ ~hell gelatin ~ -18 may be us8~ via the
oral or re~t~l r~ute.
I~:~a2U?~;E Z
~?r~paration ~ tabl~ts:
~ f~ollowing ingre~ ent~ ar~ mixe.d in the ~iven
r~lativ~ ,~r V~.J.L Lions:
st.;~nA~rdized f~verf~w leaf~ powd~r
(r~ ch in ~squiterpen~ lactone~) 60 mg
ribof~lavin 200 mg
,
2141126
!
1 2
milk ~ug~r (p~wder) 150 mg
starch 4 4 m~
talc 40 mg
stearic acid 1. 4 mg
tartar~c acid as reguired
All ingr~dient~ ar~ m~xed tho~ y. SUf f ici~nt tart3ric
acid sho~ld ~e ussd in th~ mixtur~ to adju~t ths pH to
L~_~n 2 and 6 5, prefer~bly to ~ 4.5. The mixture i~
compressQd ~nto ~lug~, which are ~ro~,d and Fcreened to 14-
16 me6h gr~n~ , which ar~ then rscom~r~s~ed into tablsts.
The tabl~ts may bs ~nteric coated, sugar coatea, filmcoatsd or ~o~ as a laminatQd tablQt. Two tabl~te ars
rQcommsn~ed for daily ing~tion.
~a~PLæ 3 :'
15 Preparat~on of in~ectable:
The ~ollowing ar~ mixed;
part~ 2500 ~g
ribofla~in 2 g
~8P wat~r for in~ection lO ml
The p~ ie ad~uste~ to ~ _an 2 and 6.s, u~ng HCl.
~he in~ ~tA~l ~ may be administered by intram~
~Pcu~o~d, or iuL~ n~ct$on. The ~.~.~Lion
~o~ be ~tored in ti~ht, light-resistant con~.~in~r~
-preferably L~ ~n 15-25 C.
E~ANPL~ ~
Preparation o~ capl~t~:
ThQ following ingr~ient~ ars ~Ye~ in the g~Ven
rslative ~.~ion~
~t~n~-rdized feverfew lsaf pow~er
(rich ~n ssSquit~rpen~ la~tone~) 60 g
r~bo~lavin 750 g
~tarch gs g
~141126
13
lactose 4 2 g
zein 4 5 g
magne~ium ~tearate 8 g
ThQ mixture of riboflavin, starch and lacto~e is granulated
with z~in (10~ in ethyl alcohol, adding additi~nal alcohol
if necessary to obtain good w~t granule~)~ The granulatsd
mixture i~ wet ~creen~ through 8 ~tainle~s 6~el ~creen
and ~ry at 110-120 F, and i~ then dry screened thr~u~l~ a
~0 ~tainle~6 eteel ~cre~n. F~V~rew lQaf pow~er i~ then
added, which ha~ been 8~r~ ~ ~ ' u~ing a ~8 e~nl~ ~tee~
~creen. The ~ompoeition i~ then mixed thoroughly,
lubricated and compL---~d into caplets. ~ach caplet should
w~igh S00 mg.
Caplets may ~e enteric coated, ~ugar coa~ed, film
coated or ~a~l a8 a lamin~tsd tabl~t.
~2~NP~ 5
,eration of D~srQn~on:
ThQ ~ollowing are ~Y9~
~ethyl c~llulo~ 0.5 g
~ ~d fs~Qrfe~ leaf ~
~rich in ~esquit~L~- e lactone~ 2.0 g
riboflavln 4,0 g
purifi~ wat~r 100 ml
bsnzoic acid (pre6ervative~ 0.1 g
~la~oring aqent (e.g.; v~ n) 0.1 ml
~he dry solids are tritur~te~ an~ ~he purifis~ ~ater i8
810wly a~ed wi~h ~rituration. The pH i8 a~u~ted to
between 3 and 6.5 u8ing ~Cl as req~ired.
The s~l~rsn~on may be adminlstQred by ing~tion. ~he
preparation ~houl~ be ~or~d i~ tight~ light-resletan~
conta~ner~, pr~rably b~tw~n lS-Z5 C
,
