Language selection

Search

Patent 2141126 Summary

Third-party information liability

Some of the information on this Web page has been provided by external sources. The Government of Canada is not responsible for the accuracy, reliability or currency of the information supplied by external sources. Users wishing to rely upon this information should consult directly with the source of the information. Content provided by external sources is not subject to official languages, privacy and accessibility requirements.

Claims and Abstract availability

Any discrepancies in the text and image of the Claims and Abstract are due to differing posting times. Text of the Claims and Abstract are posted:

  • At the time the application is open to public inspection;
  • At the time of issue of the patent (grant).
(12) Patent Application: (11) CA 2141126
(54) English Title: COMBINATIONAL DRUG FOR TREATING MIGRAINE AND OTHER ILLNESSES
(54) French Title: MEDICAMENT D'ASSOCIATION POUR LE TRAITEMENT DE LA MIGRAINE ET D'AUTRES AFFECTIONS
Status: Deemed Abandoned and Beyond the Period of Reinstatement - Pending Response to Notice of Disregarded Communication
Bibliographic Data
(51) International Patent Classification (IPC):
  • A61K 31/525 (2006.01)
(72) Inventors :
  • LAZAROWYCH, NATALIE J. (Canada)
  • O'CONNELL, MICHAEL W. (Canada)
  • PEKOS, PETER (Canada)
(73) Owners :
  • ASHBURY RESEARCH CORPORATION
(71) Applicants :
  • ASHBURY RESEARCH CORPORATION (Canada)
(74) Agent: LYNN C. SCHUMACHERSCHUMACHER, LYNN C.
(74) Associate agent:
(45) Issued:
(22) Filed Date: 1995-01-26
(41) Open to Public Inspection: 1996-07-27
Availability of licence: N/A
Dedicated to the Public: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): No

(30) Application Priority Data: None

Abstracts

English Abstract


A preparation for pharmaceutical use, especially in
the treatment of migraine, cluster headaches, arthritis and
bronchial complaints, comprises a sesquiterpene lactone
such as parthenolide and B-complex vitamins such as
riboflavin (vitamin B2), as well as a method of treating and
providing prophylaxis against such illnesses by use of such
a combination.


Claims

Note: Claims are shown in the official language in which they were submitted.


14
What is claimed is:
1. A pharmaceutical composition useful for alleviating migraine and related
headaches, arthritis and asthma comprising:
A) a sesquiterpene lactone an
b) a B-complex vitamin.
2. The composition of claim 1 wherein the sesquiterpene lactone is
provided by a source selected from the group consisting of plant materials and plant
extracts containing sesquiterpene lactone.
3. The composition of claim 1 wherein the sesquiterpene lactone is
provided by a source selected from the group consisting of feverfew leaf powder and
feverfew extract.
4. The composition of claim 1 wherein the sesquiterpene lactone is
provided by a source selected from the group consisting of Asteracea leaf powder and
Asteracea extract.
5. The composition of claim 1 wherein the sesquiterpene lactone is
provided by a source selected from the group consisting of Magnoliacea leaf powder
and Magnoliacea extract.
6. The composition of claim 1 wherein the sesquiterpene lactone is
parthenolide.
7. The composition of claim 1 wherein B-complex vitamin is riboflavin.
8. The composition of claim 3 wherein the B-complex vitamin is riboflavin.

9. The pharmaceutical preparation of claim 1 which comprises feverfew leaf
powder in combination with riboflavin.
10. The pharmaceutical preparation of claim 1 which comprises parthenolide
in combination with riboflavin.
11. The pharmaceutical composition of claim 1 in the form of a tablet,
capsule, caplet, lozenge, suspension, elixir, injectable, inhalant, suppository, slow-
release implant, slow-release patch or other topical vehicle.
12. The pharmaceutical composition of claim 3 in the form of a tablet,
capsule, caplet, lozenge, suspension, elixir, injectable, inhalant, suppository, slow-
release implant, slow-release patch or other topical vehicle.
13. A method of treating a patient suffering from an illness selected from the
group consisting of migraine, arthritis, and asthma by administering to said patient
both a source of sesquiterpene lactone and a B-complex vitamin, in a therapeutically
effective amount.
14. The method of claim 12 wherein the sesquiterpene lactone and the B-
complex vitamin are administered by independent dosage forms.
15. The method of claim 12 wherein the sesquiterpene lactone and the B-
complex vitamin are administered in the same dosage form.
16. A method of preventing or reducing the severity of an illness selected
from the group consisting of migraine, arthritis, and asthma by administering to said
patient both a source of sesquiterpene lactone and a B-complex vitamin, in a
prophylactically effective amount.

16
17. The method of claim 15 wherein the sesquiterpene lactone and the B-
complex vitamin are administered by independent dosage forms.
18. The method of claim 16 wherein the sesquiterpene lactone and the B-
complex vitamin are administered in the same dosage form.
19. The composition of claim 1 also comprising gamma linoleic acid.
20. The composition of claim 19 wherein gamma lineoleic acid source is
selected from the group consisting of evening primrose of borage oil.
21. The composition of claim 20 wherein the source of sesquiterpene lactone
is feverfew and the B-complex vitamin is riboflavin.
22. The composition of claim 1 comprising feverfew, riboflavin, and a
nonsteroidal anti-inflammatory drug.
23. The composition of claim 22 wherein the nonsteroidal anti-inflammatory
drug is of plant origin.
24. The composition of claim 23 wherein the nonsteroidal anti-inflammatory
drug is white willow bark or its extracts.

Description

Note: Descriptions are shown in the official language in which they were submitted.


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
,

Representative Drawing

Sorry, the representative drawing for patent document number 2141126 was not found.

Administrative Status

2024-08-01:As part of the Next Generation Patents (NGP) transition, the Canadian Patents Database (CPD) now contains a more detailed Event History, which replicates the Event Log of our new back-office solution.

Please note that "Inactive:" events refers to events no longer in use in our new back-office solution.

For a clearer understanding of the status of the application/patent presented on this page, the site Disclaimer , as well as the definitions for Patent , Event History , Maintenance Fee  and Payment History  should be consulted.

Event History

Description Date
Time Limit for Reversal Expired 2002-01-28
Application Not Reinstated by Deadline 2002-01-28
Deemed Abandoned - Failure to Respond to Maintenance Fee Notice 2001-01-26
Application Published (Open to Public Inspection) 1996-07-27

Abandonment History

Abandonment Date Reason Reinstatement Date
2001-01-26

Maintenance Fee

The last payment was received on 1999-12-02

Note : If the full payment has not been received on or before the date indicated, a further fee may be required which may be one of the following

  • the reinstatement fee;
  • the late payment fee; or
  • additional fee to reverse deemed expiry.

Patent fees are adjusted on the 1st of January every year. The amounts above are the current amounts if received by December 31 of the current year.
Please refer to the CIPO Patent Fees web page to see all current fee amounts.

Fee History

Fee Type Anniversary Year Due Date Paid Date
MF (application, 3rd anniv.) - small 03 1998-01-26 1998-01-21
MF (application, 4th anniv.) - small 04 1999-01-26 1999-01-21
MF (application, 5th anniv.) - small 05 2000-01-26 1999-12-02
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
ASHBURY RESEARCH CORPORATION
Past Owners on Record
MICHAEL W. O'CONNELL
NATALIE J. LAZAROWYCH
PETER PEKOS
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
Documents

To view selected files, please enter reCAPTCHA code :



To view images, click a link in the Document Description column. To download the documents, select one or more checkboxes in the first column and then click the "Download Selected in PDF format (Zip Archive)" or the "Download Selected as Single PDF" button.

List of published and non-published patent-specific documents on the CPD .

If you have any difficulty accessing content, you can call the Client Service Centre at 1-866-997-1936 or send them an e-mail at CIPO Client Service Centre.


Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Description 1996-07-26 13 480
Abstract 1996-07-26 1 11
Claims 1996-07-26 3 82
Courtesy - Abandonment Letter (Maintenance Fee) 2001-02-25 1 182
Reminder - Request for Examination 2001-09-26 1 129
Fees 1999-01-20 1 41
Fees 1999-12-01 1 42
Fees 1998-01-20 1 40
Fees 1997-01-23 1 46
Courtesy - Office Letter 1995-07-23 1 24
Prosecution correspondence 1995-08-23 2 41