CA2075113A1 - Inhalation devices - Google Patents
Inhalation devicesInfo
- Publication number
- CA2075113A1 CA2075113A1 CA002075113A CA2075113A CA2075113A1 CA 2075113 A1 CA2075113 A1 CA 2075113A1 CA 002075113 A CA002075113 A CA 002075113A CA 2075113 A CA2075113 A CA 2075113A CA 2075113 A1 CA2075113 A1 CA 2075113A1
- Authority
- CA
- Canada
- Prior art keywords
- piercer
- holder
- container
- sealed container
- body member
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
- A61M15/0033—Details of the piercing or cutting means
- A61M15/0035—Piercing means
- A61M15/0036—Piercing means hollow piercing means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
- A61M15/0033—Details of the piercing or cutting means
- A61M15/0041—Details of the piercing or cutting means with movable piercing or cutting means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
- A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
- A61M15/0048—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged in a plane, e.g. on diskettes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
- A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
- A61M15/0051—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged on a tape, e.g. strips
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/10—Preparation of respiratory gases or vapours
- A61M16/12—Preparation of respiratory gases or vapours by mixing different gases
- A61M16/122—Preparation of respiratory gases or vapours by mixing different gases with dilution
- A61M16/125—Diluting primary gas with ambient air
- A61M16/127—Diluting primary gas with ambient air by Venturi effect, i.e. entrainment mixers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/001—Particle size control
- A61M11/002—Particle size control by flow deviation causing inertial separation of transported particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
- A61M16/10—Preparation of respiratory gases or vapours
- A61M16/105—Filters
- A61M16/106—Filters in a path
- A61M16/107—Filters in a path in the inspiratory path
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/06—Solids
- A61M2202/064—Powder
Abstract
ABSTRACT
The present invention provides devices for the oral or nasal inhalation of finely divided materials such as medicinal agents and drugs.
The present invention provides devices for the oral or nasal inhalation of finely divided materials such as medicinal agents and drugs.
Description
2~75~
~ain dis~sas oX ~ ~ ~ ~ ~ to ~ to a:ra ~rosS: ~iy a~a~lc a~ a ~inf~y di~ri~ ~, 6~.g., ~n dry p~
o~ t~he medici~al a~errt in that it ~s d~sited ~:tly at t~ sit~ desi~d ar~
~rB o~ ~y a~3 ~ a~ ~ d~ ~ by ~r e~e~5. ~lterDat~ y~ the~w~_ age~rt ~ tbis ~ r~Ly beL u~ ~r may be ve~y rap~y ~ ~ t.~ bl~d st~; h~, ~neans.
A ~et:y ~ ~rhalati~ de~ î~: the delive~y oS ~ ely di~
matel:ia~ are kr~ ~n t~.a ar'c. F~ o~le, rJ,S, Pat~ 4,240,481 disclcs~;
inhalat~ rioes w~in a ~neai~ o~ Ly di~n~df3d ma~;~l ~s positi~n2d di~ ma~.
4,0~8,213) ~r a hD~ a ~.S. Paten~ ~oO 3,938,516) to di~ cw Cici~ to Qate sL~ a sa~ta=ci~l fl~w o~ air ;~ d~:Ciallt :eor sa~De d~ri~x. Far e~?le, t~e dç~rioes o~ rJ.s. Pa~: No. 3,g48,26~, ~iliz6~
vi~atable ~s tc~ dispers2 the ~inely di~i~ ma~als. See, e.g., T~.S.
Patent Nc~a. 3,~888,25'( a~ 4,995, ~5 ~ich ir~clucQ a ~m~ whic~
us~ a breath actit~ d ~peller de;rice t~ sp~ t~e ~ntaiDer o:e ~inely divided pate~T~ Nc:~. 3,507,277. A relati~ely hi~h veloci~y a~ a~r flc:w ~s req~ired to ac~i~at~ dericP~, ~ a ~xmble~ reath ~m~a~d us~s.
~ ~7 s~i~e ~ a~phen~ ~ois~.
d~ti~ o:~ a $~1 glll~ ¢ alD~t 0 It i h~ghly ~irable to ~e the use oi~ such ~lllers, e.g., in ordsr n~oe t~e liXelih~d o~ s~de el~r~s.
It can be se~n t'.~at pres~y ~ devices ~or t~ ivery o~ ~nely Devices of t'le pr~rt i~v~on ~ilize air ~law thr~ a ~.tain~ o:~
~ ~ 7 ~
~e in}~lati~ ~rioes o t~ pr~rt i~ cv~ m3r~r of ~e ~n 'chei--ability tc~ ac~atelY a~ ~ea~ly ~e t ~ely ml~s~ed,.
Yet znather major a~va~qe o~ i~halatian de~ s ~n a~:rdar~e w~th t'~
p~ ~V~C~L 1 e t h~ a;L pro~ ~ of ~ inely di~ide~ material U~ to ~ ~a ~=irat~.
h t~e prese~ inhalal~n d~rices ~ lltt:Le ~r no co~ ~~ ~hQ part cxe t~ llser, s~r~ ir~lalatic~ ~i~ hreath ca~ses t~le ~y l~Ed b~ ~ p~a~:Q ~ ~ o~ ~y d~
g a ~
o~ grea~ si~plicity ~ic~ r~2rs th~ ca~ a o~ ~ a ~lt size p t~ df~ica is a~ to re~e~ve a ~lar dis~c a~ini~ ~ltiple c=~ai~e~
o~ ~æly di~ride~ m~t~F~l. Nat ~ly d~es t;~is e=~li~nc ~e a (i~ a bo~y ~ hz~ a~ ~ passa~s~ay th~.brc~
P~ ~ ~Y ~ ~ ~ ~d In an~her s~ ~e o~ the ~ ~, the pier~
~}~ts, ~2 di~sia~s o~ t~.f3 piercer ars S~ t~at ~ thE~ seal3d t;~e ~ntain~ to the ~ pasageWay oi~ the Dier~ as it passes t~hra~ ~e 9~Uy, aLr dras~ thr~ th~ pieroer ar~ t.~ t_ passage~ay 2~7~
dlsp~s~ ~ely d~ materials i~ a sealed ~=tainer ~ich ~ no~
p least ~e se~ pier~ r pi~ th~ se~ Itair~ ~ile in the halder, q~leS~ dE~ at2 SO that wh@n the C~? ] e~d c~tair~ is F'26iti~Bd i~
p~s the sealed cc~r~ to ceat2 an ai~- passag~ay the~ehm~ air dr~
p F~. 2 is an }~sp~:lve ~ o5~ anat~ ~t o~ a derice ~iT
Pig. ~ ~ a s~ c~ 1~ 3~-3A oX th~ d~c~ sho~ i~s Fi~. 1, sh~
F~g. 3B ~s an ~nd ~ oS ~ d~ sh~ i~ Flg. 1.
F~. 3C is a plan ~ o~ ths d~vio~ sh~ in ~ig. 1~, F~g. 4 ~c c:c~ss~ n.er o~ yet an~*h~ e=:~t o~ a de~rioe o~
~e pr~ i~cs~, sl~ilar to that s~ ~ F~. 3.
Fig. 5 i5 an enlasg~ c~ss~ectional v~ew o~ t~a re~rvahly saal~d seal ~s irstact.
F~g. 6A .c a ~ti~ view o~ ~e devioe sh~ ~ Fig. 2 tal~
al~ line 6~ o~ Fig. Z~.
Fi~. 6B c an err~ ~ o~ t~e device shc~ ~ F~g. 2 sh~i~ t~e ~hala~cn ~1.
Fig. 6C l an er~ v~ew o~ the de~ric:e sho~ ~n Fig. 2 shcwir~ t~ a~
Fi~ S a plan ~r~ew o~ the devica shc~ in Fig. 2.
Fig. 7A i~ a plan v~ew o~ a disk ~ded with m~ltiple seal~ rtair~s taini~ fir~ly di~rid~ ma~er;als for use ~n the ~t i~on.
Fig. 7B is a s~de v~ew of the disk sb~n ~n Fis. 7A.
~ ~P~ 3 F~. ~C ~ a ba~ ~ o~ ths ~s3c sh~ ~n F~. 7P.
p F~. 9a.~ ara c~ secCi=~l ~ o~ yet c~h~ d~ioæ i~ a~
Fig. ;0 ~C~ a graph sh~ t~l ~etl=~ r a 24 ~ticnO
Fi~. 11 is a gra~ s}wi~ excretlcs~ o~ 3~tisol ~ a 24 ho~
.
~em~ r~t to Figs. 1 a~ 3 ~e lc ~ ~ine e~ o:e an irh~tic~n devloe o~ the pres~t i~rtion fc~r the oral i~bala~ of ~inely :m~ses a bc~y ~mber 20 ha:~rir~ 2n a~Y p~y 22 there'ch~, the ~-passageway c~s~n~ a ver~ri. ~e er~ 24 o~ the ~r ~I;er ~0 is a~ap~
. A h~Lder 40, =Qr~s~ an ~ ~ta~ r ~ a~ least ~va~ly cPsled~ ~ 60 O:e f~ely div~ ~a~ial 64, ~s ~d bcxty ~ 20. ~t least ~ piex~ 26 rem~h~y s~aled ~ntainer 60, ~zhila ~ sealed ~i~ 60 is ~n th~
4~, e~ i~n::m ~s bcc~ ~bOE 20 ar~ i~rto ~ halde~ 40. 5~ piOE~r 26 ha~3 a pas~;age~ay ~ op~ to t:be body ~er 20 ar~ th~ hal~ ~0.
~ ~.tain~ 60 ~ di3~si~d to ~ akw~s ~ holder 40 p ~ly sealed r.t~irYr C shown ~rl ~n Fig. 5. Ir~ us~, the re~y sealed ~}r~ 60 ~s pl~l ~ r 40 t~e~ e pier~æ 26 to pie~:e tqe seal~ ~tal~ 60 an~ to hold t~ a a~ a~al 66 xea~ ~ (See, e.g., F~g. 5) agair~ the ~ntainer 40~ ~e r~ble at~re, ~o device s~ ~ Fig. 4 lc sillilar t~ t~at sh~n ~n Flg. 3. ~, bc~ ~mb~r 20 t~ t~se hold~r 4a ~or a dis~ar~e ~real~er t~an t~e di3~sian oi~ ntair~ 60 to be pierc:ed. Wh~ the sealed ~rai~ 60, is placed m t"~e holder 40 a5 ~ in F~g. 4, ,~y caus~r~ the pieroer 26 to pie~e ~ sealed ~tain~ 60, the ~:l~ly di~rided T~t~:ial 64 ~c tansfer~ m the csntainer 6a to t.~ r p~ay c~ ~e piemer 2~i ~m it ls di5p~s~ U~51 inhalati by th~ us~.
~ ~7~ ~ 3 ~.ow t~ the a~r i~takQ end 27 ar~ i~t:o a~ ~eW~y 22 ol~ ~y m~OE 20 be~ dis~ ~m (i) thf3 piemed a~ ~led ~tal~s 60 ir~ t~Q o 25 ~n t~ ~i~3nt sh~ Ln ~i~. 4.
in Figs. 2 a~ 6, ~se~ a bo~y m~ber 20 h2vi~ an a~r F~ssage~y 22 th~et~, aK3 a holder 40. cne eKl 24 o~ the boc~y ~r 20 is a~aE~ for bo~ ~ 20 ' c pr~vid~ wit~ a sc:sen Z8 tc m~e i~halatic¢~ o~ ~es~
ma.terials, e.g., d!lst, ~ic~ may be pres~ irl the a~r. A ~ pi~ 26 ~or pi~ t~.e seale~ c~ain~ 60 wh~ 40, ex~e2~ds i~o ~
i~i.or o~ t".e h~lder 40 ar~ has a p~y t.~et:~o~ ~en to the bc~y memb~r 20 anc~ lder 4~.
In t.~e e~i~c s}~n ~n ~gs. 2 ar~ 6~ ~ hold~ 40 i adapted to r~3oe~ve a dis}c 70 yi~ wit~ ple oc~ta~J~J 60 as shRwn il~ Fis. 7. I~e h~ 40 ~5;Y a ~:eptacle 42 i~ æd b~ ~ bCC~ m~ 20 ar~d a CC;Ver 44 ~vably at~d to ~acle 42 by hinge nYans ~6. ~e disk 70 ~le ~ the ~older 40 is r~tably, c~ally dispc~ c~n a pin (n~st sh~n) w~ic~
t~rein.
I*.e dis~c 70 ~- p~ri~ w~th a ~cJnal la:~ ~ so tbat ~urir~
I I
2 ~ 7 ~
di.~ri~ ~s~:ial ~5 dis~ a~a~ p~ 26, 52, there~y l~ca'ci~ ~ac~
s~r~Le dosQ ~ai~ 60 ~r disp~sa tcno Dis~ o~ a g~ven ai~ ~ can A p:~e~d ~lti~;lll~ ~ disk 70 tS a~: 0.7g to 1.25 i~ in I'c will ba appar~ to t~se skilled in the art that t~ s3c 70 c~uld be ab=sp~ thr~h whiGh ai~ t dra~ u~an inhala~icn by t'~e user ~ thE
p se~ic~ 48 }~ri~ a ~ leaf ~ 50. sec~csn 48 is m~ ly ~ted in t;~e c~ 44, ~a~ 49 p~ i~ stcps to mai~ta~ secti~ 48 in c~r 44, wh~
~ver 44 tc rais~ to in~ert a disk 70 ~ seal~L ntai~s 6~.
o~ ~.e holder 40 a~l has a passaqe~Ry t;"~ethr~ open at b~ er~:!s to the holder ~0. ~.e se~d pie~er 52 is pcsitic~ relative to the ~ pieroer ~ ~ p~
26 so that they are ~le of~ pera~ to pi~ t~e seal~ ~ntain~ 60 .e seale~ ~aD~ 60 is in r~ac~e 42 an~ ratate~ ~to dispers~
pcsitian ad~a~t plexc~ 26, 50 P~=l~a 42 i~ E~ri~ w~th a s~ lea~ ~ 51 dis~c~ ~etw~
bo~ ~ber 20 aTYi disk 70, ~ tke d:lsk 7n i5 m h~ 40. 1~ ~VablR
c~er SEac~ 4a ~t~ w~h l~ ~ 50, 51 to E~rid~ t~ er~gi~
~ c[r ~ t~ ~rst ar~ s~nd p~e~ 26, 52 to pi~:Ea ~e sealQd ~ain~ 60 while in thQ ~ 40 wh~ D~le c~ sect~ 48 i~; p~
tRwa~s ~ 60 by the user.
To ~era~ the de~ic~ sha~n in ~igs. 2 and 6, the m~vable cc~ver sec~ 48 depr~ by the us~r so that piercQrs 26 and 52 pier~ the seals 61 (shown 64, b~2s~ the ta~ o~ pier~l seal 66 1c held aga1nst ~ ~ hD1der 40 ~y pier:er 26 (See Fi~. 5). -l~e ~le c~ 'csn 48 ~e held in a de~
~ti~n ut~il a~er inhalatl~n bv ~Q us~ so t.~t the pie~:0 S2, 26 will ~ ~ carrta~ w~t~L ~ ~tai~ 60 o~ f~ely ~i~rid~ mat~l 64. ~e pa~;sage of a~r ~ the per~orati~ ~n seal 62, needle 52, a:s~tair~ 60, n~dle 26, ar~l a~ FY~Y 22, vi~ally p~ finely divided m~terial 64 ~ t~ ~=laine~ 60, ~ it a~c~ w~t~ the pa~ erst~ inspired ~reath ir~to the lu~js.
of t;`~ nembar 2û ~ses a ve~hlri or a ~ in t;~ pie~xr 25 is dis~csed at or ad~ dia~r of~ the ve~h~ or t~.e ~i~poi~t ~ th~ tub~. A ve~ ic a part~a~læ~y ES~OE~ c~ati~ ~c th~ ~ passa~y 22 o~ t~ boc~ 3E3mber 7~; sha~, e.g. "n F~. 3A, 4, 6~. ar~.
8.
F~lY pre:~d e~e b~ D~3r 20 ha~ a majar ~ at ea~ en:l ("B" ~ ~ig. 6~) o~ a~3t 0.3 ~ 0.8 i~ w~t~ o~ ~i~ ~i~ 1;~ a~r ~gy 22 c3~ a ver~i, a ~ dia~ ("~" ~n Fig. 6~ at th~ ve~'s poi~ O:e ~i~ 23 ~ abaut 0.2 to 0~5 in~O ~ di~ic~n3 ar~ ~;ed up~n ~nd 24 c~f b~y Xi~OE 20 ~eir~ as~ed ~cJr ins~ticn ~sto the r~se ar ~*h o~
e3~?1e, anE~ ~ght wish the u~t to resemble a F~h3t~e pe~ sh~ i~ F~.
8 to a~ieve ~ enhan~ degree o~ ~rta~ility.
~e relati~e di~s~ o~ t~e ~:laine~s o~ ~2ely divi~d material fc~
are selec~ prov~ aa~ate delivery o~ t~ ,e:Ly di~d2d ma~ L, q~
di3;~si= of the piemer 26 which ~p~s tc~ }~ m~ber 20, ~ well ae the er~
~ ~s o~ ~ 60 ~ier~d t~eby, a~e ssle~ to ~Q
e~aF~ ~ th~ ~inely di~ mater~al 64 ac~ja~ piers:er 26. F~nely di~rided mate~al ~1GW t~e orif~ice o~ t~e ne~le 26 ls unliksly to evacL~
yet t.~e nee~le 26 ml~st pm ~ hi~ en~h to h~ld tab 66 (sh~wn ~n Fig. 5) in of~ piercer 26, thereby ups2t~ung dosage a~racy.
2~7~ 3 the cy:Ll~cal ~ntain~ 1 . s~d d~ at th~ end disp~d ad~ace~ p~
26 while ~n the dsvioe, to ~e er~ap~ oi~ nely di~id~. ~
Sea~ aOg~ ~ st~ d~ se~ 69 ~n i?i~o 5. ~ s~ ~ ~:Ce~l.y ~. ~s l~:h b~ t~ a~tslde d~ ol~ pi~xer 26 (i.~ 66 s~ c~ y p~ercer 52 1 n~rt ~siti=d so t~hal: it ~rill i~ere sp~s~ o~ ~ely di~rid~ mat~rial. }3~, pier~ 52 ~2st cierstly large ~ Fe~t ~d ~ o~ a~r.
e~cdy a pierxr 26 ~ic~ ~ a r~le, ~Erably sh~rF~ at th~
pi~ er~l to a~t a 30 t~ 45C3 ar~le. ~e r~ o~ the ne~l~ appcsit~ th~
a~: o~ ~e ne~lQ poin~ ~s typi~ly blu~t~d ~o avoid a~ng a p~ o~
seal 61 c~ ~ainer 60 ~ree. ~s sh~wn ~n Fig. 5, t~i~ leav~ a t~b 66 o~ the In a pre~e~ ~i~xnt the ~le 26 has an ~ner d~ o~ a~
0.01 t~ 0.15 i~es ar~l an a~ter di~ter of a~ 0.03 to 0.170 inc~es. S~
i~lsidE~ diæters affo~ a~2ate C~W C~ finely di~ided l~terial while sti~l t~ ~lu~dity o~ t~e ~ir.ely di~ri~ material. Far exam~le, a hi3hly fluid ~inely di~rid~ material w~d call for a ~l~er di~et~ r~le 26 t~an less ~7~
si~ to t~ e~:odime~t sh~n ~n Fi~. 4, t}~e ~ 26 ~ i~:~ ~
t~ sha~F~}d ar~l~, ~ s~cier~tly far to b~ld ta~ 66 ~ a pd~n ~OEall.y parallel~ to tha si ' ~a nsedlQ 26 a~ a~ac~ o~
~:~in~ 40, t;here~y 1~ a dear pa~Ls~a ~ar aL- ;Clow. 5~s e~æble~3 'cab 66 to r~n at'-~ to th~ ~tain~ 40 and tc~ be berst to a p~s~s a~ sh~
in Fi4 5.
In e~}~Tts wh~in t~e ne~l~ 26 ~srefdly ha~ an i~ d~ ~i~
a~t 0.01 to 0.1~ ir~es arr3 ~n a~ter dl~ ~ a~ 0.03 to 0.170 in~, s~tic~n 68 oi~ c~rtaiN~r has ar~ ~ d~ c~ a~: 0.035 t s~ticn 69 h3s a dia~ o~ ak~ 0.045 to a~ 0.1~0 ~es. In a y ~e~. ~s pie~ 2~ s an ~ ~ o~ a~
0 045 ir~ ar~:i. aT~ a~er d~æeter o~ abc~t 0.062 ir~hes ar~l the sect~n 68 ~
60 has an ~ di~er ~ ab~ 0.070 ir~es ar~ sec~an 69 ha3 an 1s~r ~iamF~r of abaut O.C80 inc'~.
:~ e=~ists of 'c"~ pres~rt irn~sti~ C~l i*~lu~e a sec~ pier~ 52, suc~ as thcss sh~ ~ F_ss. 2, 6 a~ 8, the sea:~ pier:e:r 52 i~ also ~e~erably si~rF~ a~ t.'~e pi~cir~ end to a}:~t a 3û t~ 45C~ ar~le a~ the p~ 52 ? C typically a~ut 10 to 15~ 9reatel:' t~'~ 'ChR l~Er dia3~æ c~e pie~ 26.
e em~i~e~t shawn ~n Figs. 2 arrl 6, lea~ u~s 50 ar~ 51 are pre~erably stainless st~l ar~ are ab~t O.C05 to O.OlS inc~es, ~re pre~exably -- l6 --~ ~ 7 ~
0.~10 ~ 0.012 ~-~h~. ~ 1 ~ p ~ c ~ ~ also ke ~ d b sE~s may b~ u~l~able.
exzm~le, in e=~C3 ~e~in th~ pi~:er 26 is a redle, t~a ~e~ i~
a:lrrtair.er S prq~ri~ w~th a ~ sec~ 68 an:3 a sec~ ssGticsn 0, rs~er ~ d~er chan sec~ 6a, ag sh~ in, e.~., Fig. 5. In y~t ath~
e=~i~nts of the pr~t ~e~an, e.g., a~ sh~n ~n Fig. 8, æcticn 6B o~
~ntainer 6q tapers a~a~ly. rrh;~ lows a greater volume o~ ly di~i~ material to ba lo~ w~thin a gi~ren dep~. Fo:r prc:Fer ~vaalatic~ o~
t.~e e~t sh~n in Fi~. 4, the ~ di~Et:er oi~ s~an 6~ o~ th2 c~ainer 60 ~ ab~t 10 to lS% la~y~ t~,an t~ e 26.
In e~5 s~ar to that~ sh~wn ~n Fig. 4, bec~use t~e ~ ly d:iv~ed matar;~l ls ~ar~sf~d to the needle ~c it ~?ie~:es the c~tair.er, t~e e ~arrta~ is ~:rnly a~ 10 t~ 1S% lzrger t~n t.~P c~ter di~ o~ r~e 26 t~ ~e a~y res~e o~ ~ly di~ at~al whic~
3m;~ts oi~ ~æly di~ed mater;al ~ar~7~r~ ~m ab~t 0.1 to 2S IDilligra~s-~0 6~ a~ t~e su~ ~S ~ ~inely divi~ ~t~al. See, e.g., Fi~o 5 m~ space 65 a~ t~ ~y d~ ma~ 64 t~ r~n lo~s~, ~g ~he particle size o~ t1~ ~y di.~.ded D~ to b2~ dali.~e~xd also pa:tic3e s~ze C d~te~i~, ~n part, by the ~de oi~ deli~Jery, i.e., orally cr possible F~rti~ o~ the dc6Q o~ 1y di~rided ~ate~ial i~to t~e lur~s ar~ to ~ir~ particle size ar~ greater ~lcw o~ mu,~3h the device o the p~t a c~ianal pier~able material, su~h as a plas'.~c or metal film, usir~
D~hods known to th~e skilled ~n the ar~_. See,e.g.~ L 61 in Fi~. S. In su~ em~}~s, t~e t'.lic~ss of thæ film is aka~ 0.502 to a.ca4 ~nclles.
~7~
~ is ~vabl~ sealed, the r~a seal ~pr~ses a h~:ic ~o~l T~7~ple ~taine~s 60 are disp~ in d~;k 70, th~ disk 70 ~c 'cypiG~lly ma~Prial 64 to be di4~ ~ ~en ~ to the m~lltiple :taiD~s 60 disp~ ~n disk 7U ar~ the ~r:t~in~s 60 ar~ th~L he~t:ally se~led ~y s~ th~ ather si~e o~ disk 70 e~t~er wit~ a re~le seal ~r w~t~
p~ercable sealir~ ~ate~al.
a~ar~ ~ m t;"~a art. lb ens~ s~le ma~ fac~e of~ SUC~ dEYi.C~`s a~d ~in~s, i~ ~ ~wnea~ t:a us~ a rea~ily y~ssable plastic ~ere suita~le.
It will be aE~?ar~ to ~.e skilled. a~ ~n li~jht oi~ t'~ i~3s aî
the E~eserrt ~ersticn t~.at c~ati~ns o~ ~ody ~mker 20, hol~er 40, pier~er 26 a~Vor aK1 piercers 26, 52 ~;"er than t~se ~n may be util~zed wit~t _ 19 _ 2~7~13 ~ r ~mpl~, hOLder 40 may ba ~Ct~ t~ 3 bCdY ~æmb19r 20 a~ ~C:US
a~1eS aS ~ a~d in Fig. 9: ~ig. 3A Sh~ a 4S a~l~, 2'iss 9B ar~d 9C
a 90 a~Le, a~ c~. 9D a 30 æ~le. In Yet 2n~th~ e~rt Sh~ 2n . 8, ~O*Y m~er 2~, hclder 40, ar~ Pier~ Z6 ar~ 52 ar~ ar~ar~ ~.n e~ .e., at 0 an~LQ. Ft~8, ~ ~ ShC~ i.n. F~. ~3 ~3 In U~, t~ ~r 44 OI~ t~ ~i~ ShGW~ ~n ~g. 8 C re~d, t~
Sea1ed 51eYir~r 60 iS ~ n t~2e hO1de~ 4~, ar~d th~ ~m Sea1 0*
CX~a~ 60 ;~ Pieroed. ~e Ct~Ver 44 i5 I:eP1a~ arY1 ~;Sad }~3ne tO Pie~oe ~011~5 aVer~11 1er~t:h, aka~t 3 tC~ 6 ~nG~eg; di3~er, a~t 0.25 tO 0.75 ir~; 1er~'1 0~ Y D~mber 20~ a~t 2 ~0 4 i~2:h~; 1erS~th 0~ rer 44, aba~t 1.5 tO ~.5 ~ rCer 26, a~ 1 tO 1.. 75 ~.eS;
1er3~th 0~ P~ 52, aba~t 0.375 tO 0.75 in~es. ~:n Cn~ SUC~ ~Xr:a:ee~
wa~a ~lly aka~t 25 ~te~:s p6~ ml~:L~a. ~ d.ime~5~g 0~ vioe wera as ~0~ CVera11 1ergt:~ 0~ abou~ 3.375 ~:~es; an ~nside dl~ of abalt 0.32 ~r;'~.es at t~.e wi~t se~c~ ar~i 0.25 i~s~es at t'~.e n~ sec.~_~n o~ 'C~.Q
Ve~; b~Y me~ 20 1Y~;~ Oi~ 2.25 i~es; holder 40 1~ C~ a1~t 0.375 in~'~eg; Pieme~ 2~ 1er~L ~ a~t 1.1 ~ C; and. P~ er 5Z 1 a~ 0 . 5 1*e ~:e~al d~cer ~¢ ~:ed to res~ ~e a:Lr ~.a~ ~ 1ivery. Far e~?le, 1;'1e n~t sec'-,~ c~f t'.Q ver~turi can be re~ to aba~t 0.187 2~7~ 3 at a 30a ar~le fc~r c~ eo~ ~n useO o~Pr than d~OEe~, the us~r~ an inhalatian devica si~ilæ to t'~t s~ ~n Fi~s. 1 and 3A was cc~a~
r~c~piersts Gf the }~1 fc r its pres~
n~ ~een ~1 t~ ~y t~e liver. It LS .~la~l t~lat ~1 ti501 LS i~, a Fig. 10 sh~s t~at Dnre ~es ~3~1 was ex~ ~n a 24 h~r df~rioe oî t'.~e preser~ i~tic~ as cc~an~ wit;1l ~es~cr10 Fig., 11 sh~ t~
inhaled ~rtiscl ~s ~re di~ly available ~or ~icn ~n the ur~e at an ~ ~ 7 ~ t the alveolæ epithelium ancl, ~us, els~d sys~ic cir~la~ian ~n a manr~
alm~st e~ival~ to delivery oi~ EI3-cortisoL i~v~nausly. Irl c~T~æ, 'che A ds~7ic~ si~ilar to t~at ~n ~ Figs. 1 ar~ 3A ~as tes~d to dete~mi~
its delivery accuracy.
A con'cainer simila~ ~t ~lawn ~n Figs. 3A ar~l 5 was ~ilLed with aba~t 3.24 ~ o~ finely divid~l material and plaa~ in thie holder ~0 o:e a devic~
s;m-~æ to that shawn in Figs. 1 and 3A. It was nc~t necessary to provide the ~rltainer with a remaveable seal 62 because the finely divided material was dis~arye was }:y h~ vacuLml pump ~th a ~rolu~e a~tely ~al to the human lung. A cansta~ stml~ was used in disp~s~ng to min~m~ze var~atic~n.
we~hed a~, and the residLle o~ finely div~d~ matEr~al det~in~. ~rhis pr~cess was repeat~ t~-five ti~s. qhe ~ainer was vir~ally purgecl w~ each delivery, ar~l the resi~ ~n~ was very cansta~ arxl very small.. rhUs, ve~y aca~rate dose delivery was achieved ~y the use of a d~ica rhis ~;ve~sti~n will ~e ~t}~ I=~stc~ with reference t;o the fo1 examples which are pur~ly exemplary in nature an~ are not meant to l~it the scaDe of the inverTtic~.
~7~13 E~
d~ice si~ilar to t~h~t shc~ igs. 1 and 3A w us~d ~ t~s }~e.
~ollaw~: 100 ~ a~ ~tisol w wei~ ~ a clean c::u~e.. 200 D~ c~
a vial nta~ni~ 0.5ml o~ water ar~l 5.0 ml o~ pi~f~uar. ~tely 6,523,223 ~ts per mir~te~m3 was prepar~, gi~ a speci~ic ætiv~y ~o~
3~ti~1 of 1,279, 063 cs:~l~tsfS~i~/~.
~.
lay@r cqr~matc~ap~.
2 ~
0 d~ns~ t~at o~ otal c~ per min3~ c~ a F~. 11 ~h~ c~ts FOE mi~t~ o:e I~ E3~sol ex~ ~v~ a 24 o~ ~e ~d ~., ~ticn.
a~ c~ai~.
- 24 _
~ain dis~sas oX ~ ~ ~ ~ ~ to ~ to a:ra ~rosS: ~iy a~a~lc a~ a ~inf~y di~ri~ ~, 6~.g., ~n dry p~
o~ t~he medici~al a~errt in that it ~s d~sited ~:tly at t~ sit~ desi~d ar~
~rB o~ ~y a~3 ~ a~ ~ d~ ~ by ~r e~e~5. ~lterDat~ y~ the~w~_ age~rt ~ tbis ~ r~Ly beL u~ ~r may be ve~y rap~y ~ ~ t.~ bl~d st~; h~, ~neans.
A ~et:y ~ ~rhalati~ de~ î~: the delive~y oS ~ ely di~
matel:ia~ are kr~ ~n t~.a ar'c. F~ o~le, rJ,S, Pat~ 4,240,481 disclcs~;
inhalat~ rioes w~in a ~neai~ o~ Ly di~n~df3d ma~;~l ~s positi~n2d di~ ma~.
4,0~8,213) ~r a hD~ a ~.S. Paten~ ~oO 3,938,516) to di~ cw Cici~ to Qate sL~ a sa~ta=ci~l fl~w o~ air ;~ d~:Ciallt :eor sa~De d~ri~x. Far e~?le, t~e dç~rioes o~ rJ.s. Pa~: No. 3,g48,26~, ~iliz6~
vi~atable ~s tc~ dispers2 the ~inely di~i~ ma~als. See, e.g., T~.S.
Patent Nc~a. 3,~888,25'( a~ 4,995, ~5 ~ich ir~clucQ a ~m~ whic~
us~ a breath actit~ d ~peller de;rice t~ sp~ t~e ~ntaiDer o:e ~inely divided pate~T~ Nc:~. 3,507,277. A relati~ely hi~h veloci~y a~ a~r flc:w ~s req~ired to ac~i~at~ dericP~, ~ a ~xmble~ reath ~m~a~d us~s.
~ ~7 s~i~e ~ a~phen~ ~ois~.
d~ti~ o:~ a $~1 glll~ ¢ alD~t 0 It i h~ghly ~irable to ~e the use oi~ such ~lllers, e.g., in ordsr n~oe t~e liXelih~d o~ s~de el~r~s.
It can be se~n t'.~at pres~y ~ devices ~or t~ ivery o~ ~nely Devices of t'le pr~rt i~v~on ~ilize air ~law thr~ a ~.tain~ o:~
~ ~ 7 ~
~e in}~lati~ ~rioes o t~ pr~rt i~ cv~ m3r~r of ~e ~n 'chei--ability tc~ ac~atelY a~ ~ea~ly ~e t ~ely ml~s~ed,.
Yet znather major a~va~qe o~ i~halatian de~ s ~n a~:rdar~e w~th t'~
p~ ~V~C~L 1 e t h~ a;L pro~ ~ of ~ inely di~ide~ material U~ to ~ ~a ~=irat~.
h t~e prese~ inhalal~n d~rices ~ lltt:Le ~r no co~ ~~ ~hQ part cxe t~ llser, s~r~ ir~lalatic~ ~i~ hreath ca~ses t~le ~y l~Ed b~ ~ p~a~:Q ~ ~ o~ ~y d~
g a ~
o~ grea~ si~plicity ~ic~ r~2rs th~ ca~ a o~ ~ a ~lt size p t~ df~ica is a~ to re~e~ve a ~lar dis~c a~ini~ ~ltiple c=~ai~e~
o~ ~æly di~ride~ m~t~F~l. Nat ~ly d~es t;~is e=~li~nc ~e a (i~ a bo~y ~ hz~ a~ ~ passa~s~ay th~.brc~
P~ ~ ~Y ~ ~ ~ ~d In an~her s~ ~e o~ the ~ ~, the pier~
~}~ts, ~2 di~sia~s o~ t~.f3 piercer ars S~ t~at ~ thE~ seal3d t;~e ~ntain~ to the ~ pasageWay oi~ the Dier~ as it passes t~hra~ ~e 9~Uy, aLr dras~ thr~ th~ pieroer ar~ t.~ t_ passage~ay 2~7~
dlsp~s~ ~ely d~ materials i~ a sealed ~=tainer ~ich ~ no~
p least ~e se~ pier~ r pi~ th~ se~ Itair~ ~ile in the halder, q~leS~ dE~ at2 SO that wh@n the C~? ] e~d c~tair~ is F'26iti~Bd i~
p~s the sealed cc~r~ to ceat2 an ai~- passag~ay the~ehm~ air dr~
p F~. 2 is an }~sp~:lve ~ o5~ anat~ ~t o~ a derice ~iT
Pig. ~ ~ a s~ c~ 1~ 3~-3A oX th~ d~c~ sho~ i~s Fi~. 1, sh~
F~g. 3B ~s an ~nd ~ oS ~ d~ sh~ i~ Flg. 1.
F~. 3C is a plan ~ o~ ths d~vio~ sh~ in ~ig. 1~, F~g. 4 ~c c:c~ss~ n.er o~ yet an~*h~ e=:~t o~ a de~rioe o~
~e pr~ i~cs~, sl~ilar to that s~ ~ F~. 3.
Fig. 5 i5 an enlasg~ c~ss~ectional v~ew o~ t~a re~rvahly saal~d seal ~s irstact.
F~g. 6A .c a ~ti~ view o~ ~e devioe sh~ ~ Fig. 2 tal~
al~ line 6~ o~ Fig. Z~.
Fi~. 6B c an err~ ~ o~ t~e device shc~ ~ F~g. 2 sh~i~ t~e ~hala~cn ~1.
Fig. 6C l an er~ v~ew o~ the de~ric:e sho~ ~n Fig. 2 shcwir~ t~ a~
Fi~ S a plan ~r~ew o~ the devica shc~ in Fig. 2.
Fig. 7A i~ a plan v~ew o~ a disk ~ded with m~ltiple seal~ rtair~s taini~ fir~ly di~rid~ ma~er;als for use ~n the ~t i~on.
Fig. 7B is a s~de v~ew of the disk sb~n ~n Fis. 7A.
~ ~P~ 3 F~. ~C ~ a ba~ ~ o~ ths ~s3c sh~ ~n F~. 7P.
p F~. 9a.~ ara c~ secCi=~l ~ o~ yet c~h~ d~ioæ i~ a~
Fig. ;0 ~C~ a graph sh~ t~l ~etl=~ r a 24 ~ticnO
Fi~. 11 is a gra~ s}wi~ excretlcs~ o~ 3~tisol ~ a 24 ho~
.
~em~ r~t to Figs. 1 a~ 3 ~e lc ~ ~ine e~ o:e an irh~tic~n devloe o~ the pres~t i~rtion fc~r the oral i~bala~ of ~inely :m~ses a bc~y ~mber 20 ha:~rir~ 2n a~Y p~y 22 there'ch~, the ~-passageway c~s~n~ a ver~ri. ~e er~ 24 o~ the ~r ~I;er ~0 is a~ap~
. A h~Lder 40, =Qr~s~ an ~ ~ta~ r ~ a~ least ~va~ly cPsled~ ~ 60 O:e f~ely div~ ~a~ial 64, ~s ~d bcxty ~ 20. ~t least ~ piex~ 26 rem~h~y s~aled ~ntainer 60, ~zhila ~ sealed ~i~ 60 is ~n th~
4~, e~ i~n::m ~s bcc~ ~bOE 20 ar~ i~rto ~ halde~ 40. 5~ piOE~r 26 ha~3 a pas~;age~ay ~ op~ to t:be body ~er 20 ar~ th~ hal~ ~0.
~ ~.tain~ 60 ~ di3~si~d to ~ akw~s ~ holder 40 p ~ly sealed r.t~irYr C shown ~rl ~n Fig. 5. Ir~ us~, the re~y sealed ~}r~ 60 ~s pl~l ~ r 40 t~e~ e pier~æ 26 to pie~:e tqe seal~ ~tal~ 60 an~ to hold t~ a a~ a~al 66 xea~ ~ (See, e.g., F~g. 5) agair~ the ~ntainer 40~ ~e r~ble at~re, ~o device s~ ~ Fig. 4 lc sillilar t~ t~at sh~n ~n Flg. 3. ~, bc~ ~mb~r 20 t~ t~se hold~r 4a ~or a dis~ar~e ~real~er t~an t~e di3~sian oi~ ntair~ 60 to be pierc:ed. Wh~ the sealed ~rai~ 60, is placed m t"~e holder 40 a5 ~ in F~g. 4, ,~y caus~r~ the pieroer 26 to pie~e ~ sealed ~tain~ 60, the ~:l~ly di~rided T~t~:ial 64 ~c tansfer~ m the csntainer 6a to t.~ r p~ay c~ ~e piemer 2~i ~m it ls di5p~s~ U~51 inhalati by th~ us~.
~ ~7~ ~ 3 ~.ow t~ the a~r i~takQ end 27 ar~ i~t:o a~ ~eW~y 22 ol~ ~y m~OE 20 be~ dis~ ~m (i) thf3 piemed a~ ~led ~tal~s 60 ir~ t~Q o 25 ~n t~ ~i~3nt sh~ Ln ~i~. 4.
in Figs. 2 a~ 6, ~se~ a bo~y m~ber 20 h2vi~ an a~r F~ssage~y 22 th~et~, aK3 a holder 40. cne eKl 24 o~ the boc~y ~r 20 is a~aE~ for bo~ ~ 20 ' c pr~vid~ wit~ a sc:sen Z8 tc m~e i~halatic¢~ o~ ~es~
ma.terials, e.g., d!lst, ~ic~ may be pres~ irl the a~r. A ~ pi~ 26 ~or pi~ t~.e seale~ c~ain~ 60 wh~ 40, ex~e2~ds i~o ~
i~i.or o~ t".e h~lder 40 ar~ has a p~y t.~et:~o~ ~en to the bc~y memb~r 20 anc~ lder 4~.
In t.~e e~i~c s}~n ~n ~gs. 2 ar~ 6~ ~ hold~ 40 i adapted to r~3oe~ve a dis}c 70 yi~ wit~ ple oc~ta~J~J 60 as shRwn il~ Fis. 7. I~e h~ 40 ~5;Y a ~:eptacle 42 i~ æd b~ ~ bCC~ m~ 20 ar~d a CC;Ver 44 ~vably at~d to ~acle 42 by hinge nYans ~6. ~e disk 70 ~le ~ the ~older 40 is r~tably, c~ally dispc~ c~n a pin (n~st sh~n) w~ic~
t~rein.
I*.e dis~c 70 ~- p~ri~ w~th a ~cJnal la:~ ~ so tbat ~urir~
I I
2 ~ 7 ~
di.~ri~ ~s~:ial ~5 dis~ a~a~ p~ 26, 52, there~y l~ca'ci~ ~ac~
s~r~Le dosQ ~ai~ 60 ~r disp~sa tcno Dis~ o~ a g~ven ai~ ~ can A p:~e~d ~lti~;lll~ ~ disk 70 tS a~: 0.7g to 1.25 i~ in I'c will ba appar~ to t~se skilled in the art that t~ s3c 70 c~uld be ab=sp~ thr~h whiGh ai~ t dra~ u~an inhala~icn by t'~e user ~ thE
p se~ic~ 48 }~ri~ a ~ leaf ~ 50. sec~csn 48 is m~ ly ~ted in t;~e c~ 44, ~a~ 49 p~ i~ stcps to mai~ta~ secti~ 48 in c~r 44, wh~
~ver 44 tc rais~ to in~ert a disk 70 ~ seal~L ntai~s 6~.
o~ ~.e holder 40 a~l has a passaqe~Ry t;"~ethr~ open at b~ er~:!s to the holder ~0. ~.e se~d pie~er 52 is pcsitic~ relative to the ~ pieroer ~ ~ p~
26 so that they are ~le of~ pera~ to pi~ t~e seal~ ~ntain~ 60 .e seale~ ~aD~ 60 is in r~ac~e 42 an~ ratate~ ~to dispers~
pcsitian ad~a~t plexc~ 26, 50 P~=l~a 42 i~ E~ri~ w~th a s~ lea~ ~ 51 dis~c~ ~etw~
bo~ ~ber 20 aTYi disk 70, ~ tke d:lsk 7n i5 m h~ 40. 1~ ~VablR
c~er SEac~ 4a ~t~ w~h l~ ~ 50, 51 to E~rid~ t~ er~gi~
~ c[r ~ t~ ~rst ar~ s~nd p~e~ 26, 52 to pi~:Ea ~e sealQd ~ain~ 60 while in thQ ~ 40 wh~ D~le c~ sect~ 48 i~; p~
tRwa~s ~ 60 by the user.
To ~era~ the de~ic~ sha~n in ~igs. 2 and 6, the m~vable cc~ver sec~ 48 depr~ by the us~r so that piercQrs 26 and 52 pier~ the seals 61 (shown 64, b~2s~ the ta~ o~ pier~l seal 66 1c held aga1nst ~ ~ hD1der 40 ~y pier:er 26 (See Fi~. 5). -l~e ~le c~ 'csn 48 ~e held in a de~
~ti~n ut~il a~er inhalatl~n bv ~Q us~ so t.~t the pie~:0 S2, 26 will ~ ~ carrta~ w~t~L ~ ~tai~ 60 o~ f~ely ~i~rid~ mat~l 64. ~e pa~;sage of a~r ~ the per~orati~ ~n seal 62, needle 52, a:s~tair~ 60, n~dle 26, ar~l a~ FY~Y 22, vi~ally p~ finely divided m~terial 64 ~ t~ ~=laine~ 60, ~ it a~c~ w~t~ the pa~ erst~ inspired ~reath ir~to the lu~js.
of t;`~ nembar 2û ~ses a ve~hlri or a ~ in t;~ pie~xr 25 is dis~csed at or ad~ dia~r of~ the ve~h~ or t~.e ~i~poi~t ~ th~ tub~. A ve~ ic a part~a~læ~y ES~OE~ c~ati~ ~c th~ ~ passa~y 22 o~ t~ boc~ 3E3mber 7~; sha~, e.g. "n F~. 3A, 4, 6~. ar~.
8.
F~lY pre:~d e~e b~ D~3r 20 ha~ a majar ~ at ea~ en:l ("B" ~ ~ig. 6~) o~ a~3t 0.3 ~ 0.8 i~ w~t~ o~ ~i~ ~i~ 1;~ a~r ~gy 22 c3~ a ver~i, a ~ dia~ ("~" ~n Fig. 6~ at th~ ve~'s poi~ O:e ~i~ 23 ~ abaut 0.2 to 0~5 in~O ~ di~ic~n3 ar~ ~;ed up~n ~nd 24 c~f b~y Xi~OE 20 ~eir~ as~ed ~cJr ins~ticn ~sto the r~se ar ~*h o~
e3~?1e, anE~ ~ght wish the u~t to resemble a F~h3t~e pe~ sh~ i~ F~.
8 to a~ieve ~ enhan~ degree o~ ~rta~ility.
~e relati~e di~s~ o~ t~e ~:laine~s o~ ~2ely divi~d material fc~
are selec~ prov~ aa~ate delivery o~ t~ ,e:Ly di~d2d ma~ L, q~
di3;~si= of the piemer 26 which ~p~s tc~ }~ m~ber 20, ~ well ae the er~
~ ~s o~ ~ 60 ~ier~d t~eby, a~e ssle~ to ~Q
e~aF~ ~ th~ ~inely di~ mater~al 64 ac~ja~ piers:er 26. F~nely di~rided mate~al ~1GW t~e orif~ice o~ t~e ne~le 26 ls unliksly to evacL~
yet t.~e nee~le 26 ml~st pm ~ hi~ en~h to h~ld tab 66 (sh~wn ~n Fig. 5) in of~ piercer 26, thereby ups2t~ung dosage a~racy.
2~7~ 3 the cy:Ll~cal ~ntain~ 1 . s~d d~ at th~ end disp~d ad~ace~ p~
26 while ~n the dsvioe, to ~e er~ap~ oi~ nely di~id~. ~
Sea~ aOg~ ~ st~ d~ se~ 69 ~n i?i~o 5. ~ s~ ~ ~:Ce~l.y ~. ~s l~:h b~ t~ a~tslde d~ ol~ pi~xer 26 (i.~ 66 s~ c~ y p~ercer 52 1 n~rt ~siti=d so t~hal: it ~rill i~ere sp~s~ o~ ~ely di~rid~ mat~rial. }3~, pier~ 52 ~2st cierstly large ~ Fe~t ~d ~ o~ a~r.
e~cdy a pierxr 26 ~ic~ ~ a r~le, ~Erably sh~rF~ at th~
pi~ er~l to a~t a 30 t~ 45C3 ar~le. ~e r~ o~ the ne~l~ appcsit~ th~
a~: o~ ~e ne~lQ poin~ ~s typi~ly blu~t~d ~o avoid a~ng a p~ o~
seal 61 c~ ~ainer 60 ~ree. ~s sh~wn ~n Fig. 5, t~i~ leav~ a t~b 66 o~ the In a pre~e~ ~i~xnt the ~le 26 has an ~ner d~ o~ a~
0.01 t~ 0.15 i~es ar~l an a~ter di~ter of a~ 0.03 to 0.170 inc~es. S~
i~lsidE~ diæters affo~ a~2ate C~W C~ finely di~ided l~terial while sti~l t~ ~lu~dity o~ t~e ~ir.ely di~ri~ material. Far exam~le, a hi3hly fluid ~inely di~rid~ material w~d call for a ~l~er di~et~ r~le 26 t~an less ~7~
si~ to t~ e~:odime~t sh~n ~n Fi~. 4, t}~e ~ 26 ~ i~:~ ~
t~ sha~F~}d ar~l~, ~ s~cier~tly far to b~ld ta~ 66 ~ a pd~n ~OEall.y parallel~ to tha si ' ~a nsedlQ 26 a~ a~ac~ o~
~:~in~ 40, t;here~y 1~ a dear pa~Ls~a ~ar aL- ;Clow. 5~s e~æble~3 'cab 66 to r~n at'-~ to th~ ~tain~ 40 and tc~ be berst to a p~s~s a~ sh~
in Fi4 5.
In e~}~Tts wh~in t~e ne~l~ 26 ~srefdly ha~ an i~ d~ ~i~
a~t 0.01 to 0.1~ ir~es arr3 ~n a~ter dl~ ~ a~ 0.03 to 0.170 in~, s~tic~n 68 oi~ c~rtaiN~r has ar~ ~ d~ c~ a~: 0.035 t s~ticn 69 h3s a dia~ o~ ak~ 0.045 to a~ 0.1~0 ~es. In a y ~e~. ~s pie~ 2~ s an ~ ~ o~ a~
0 045 ir~ ar~:i. aT~ a~er d~æeter o~ abc~t 0.062 ir~hes ar~l the sect~n 68 ~
60 has an ~ di~er ~ ab~ 0.070 ir~es ar~ sec~an 69 ha3 an 1s~r ~iamF~r of abaut O.C80 inc'~.
:~ e=~ists of 'c"~ pres~rt irn~sti~ C~l i*~lu~e a sec~ pier~ 52, suc~ as thcss sh~ ~ F_ss. 2, 6 a~ 8, the sea:~ pier:e:r 52 i~ also ~e~erably si~rF~ a~ t.'~e pi~cir~ end to a}:~t a 3û t~ 45C~ ar~le a~ the p~ 52 ? C typically a~ut 10 to 15~ 9reatel:' t~'~ 'ChR l~Er dia3~æ c~e pie~ 26.
e em~i~e~t shawn ~n Figs. 2 arrl 6, lea~ u~s 50 ar~ 51 are pre~erably stainless st~l ar~ are ab~t O.C05 to O.OlS inc~es, ~re pre~exably -- l6 --~ ~ 7 ~
0.~10 ~ 0.012 ~-~h~. ~ 1 ~ p ~ c ~ ~ also ke ~ d b sE~s may b~ u~l~able.
exzm~le, in e=~C3 ~e~in th~ pi~:er 26 is a redle, t~a ~e~ i~
a:lrrtair.er S prq~ri~ w~th a ~ sec~ 68 an:3 a sec~ ssGticsn 0, rs~er ~ d~er chan sec~ 6a, ag sh~ in, e.~., Fig. 5. In y~t ath~
e=~i~nts of the pr~t ~e~an, e.g., a~ sh~n ~n Fig. 8, æcticn 6B o~
~ntainer 6q tapers a~a~ly. rrh;~ lows a greater volume o~ ly di~i~ material to ba lo~ w~thin a gi~ren dep~. Fo:r prc:Fer ~vaalatic~ o~
t.~e e~t sh~n in Fi~. 4, the ~ di~Et:er oi~ s~an 6~ o~ th2 c~ainer 60 ~ ab~t 10 to lS% la~y~ t~,an t~ e 26.
In e~5 s~ar to that~ sh~wn ~n Fig. 4, bec~use t~e ~ ly d:iv~ed matar;~l ls ~ar~sf~d to the needle ~c it ~?ie~:es the c~tair.er, t~e e ~arrta~ is ~:rnly a~ 10 t~ 1S% lzrger t~n t.~P c~ter di~ o~ r~e 26 t~ ~e a~y res~e o~ ~ly di~ at~al whic~
3m;~ts oi~ ~æly di~ed mater;al ~ar~7~r~ ~m ab~t 0.1 to 2S IDilligra~s-~0 6~ a~ t~e su~ ~S ~ ~inely divi~ ~t~al. See, e.g., Fi~o 5 m~ space 65 a~ t~ ~y d~ ma~ 64 t~ r~n lo~s~, ~g ~he particle size o~ t1~ ~y di.~.ded D~ to b2~ dali.~e~xd also pa:tic3e s~ze C d~te~i~, ~n part, by the ~de oi~ deli~Jery, i.e., orally cr possible F~rti~ o~ the dc6Q o~ 1y di~rided ~ate~ial i~to t~e lur~s ar~ to ~ir~ particle size ar~ greater ~lcw o~ mu,~3h the device o the p~t a c~ianal pier~able material, su~h as a plas'.~c or metal film, usir~
D~hods known to th~e skilled ~n the ar~_. See,e.g.~ L 61 in Fi~. S. In su~ em~}~s, t~e t'.lic~ss of thæ film is aka~ 0.502 to a.ca4 ~nclles.
~7~
~ is ~vabl~ sealed, the r~a seal ~pr~ses a h~:ic ~o~l T~7~ple ~taine~s 60 are disp~ in d~;k 70, th~ disk 70 ~c 'cypiG~lly ma~Prial 64 to be di4~ ~ ~en ~ to the m~lltiple :taiD~s 60 disp~ ~n disk 7U ar~ the ~r:t~in~s 60 ar~ th~L he~t:ally se~led ~y s~ th~ ather si~e o~ disk 70 e~t~er wit~ a re~le seal ~r w~t~
p~ercable sealir~ ~ate~al.
a~ar~ ~ m t;"~a art. lb ens~ s~le ma~ fac~e of~ SUC~ dEYi.C~`s a~d ~in~s, i~ ~ ~wnea~ t:a us~ a rea~ily y~ssable plastic ~ere suita~le.
It will be aE~?ar~ to ~.e skilled. a~ ~n li~jht oi~ t'~ i~3s aî
the E~eserrt ~ersticn t~.at c~ati~ns o~ ~ody ~mker 20, hol~er 40, pier~er 26 a~Vor aK1 piercers 26, 52 ~;"er than t~se ~n may be util~zed wit~t _ 19 _ 2~7~13 ~ r ~mpl~, hOLder 40 may ba ~Ct~ t~ 3 bCdY ~æmb19r 20 a~ ~C:US
a~1eS aS ~ a~d in Fig. 9: ~ig. 3A Sh~ a 4S a~l~, 2'iss 9B ar~d 9C
a 90 a~Le, a~ c~. 9D a 30 æ~le. In Yet 2n~th~ e~rt Sh~ 2n . 8, ~O*Y m~er 2~, hclder 40, ar~ Pier~ Z6 ar~ 52 ar~ ar~ar~ ~.n e~ .e., at 0 an~LQ. Ft~8, ~ ~ ShC~ i.n. F~. ~3 ~3 In U~, t~ ~r 44 OI~ t~ ~i~ ShGW~ ~n ~g. 8 C re~d, t~
Sea1ed 51eYir~r 60 iS ~ n t~2e hO1de~ 4~, ar~d th~ ~m Sea1 0*
CX~a~ 60 ;~ Pieroed. ~e Ct~Ver 44 i5 I:eP1a~ arY1 ~;Sad }~3ne tO Pie~oe ~011~5 aVer~11 1er~t:h, aka~t 3 tC~ 6 ~nG~eg; di3~er, a~t 0.25 tO 0.75 ir~; 1er~'1 0~ Y D~mber 20~ a~t 2 ~0 4 i~2:h~; 1erS~th 0~ rer 44, aba~t 1.5 tO ~.5 ~ rCer 26, a~ 1 tO 1.. 75 ~.eS;
1er3~th 0~ P~ 52, aba~t 0.375 tO 0.75 in~es. ~:n Cn~ SUC~ ~Xr:a:ee~
wa~a ~lly aka~t 25 ~te~:s p6~ ml~:L~a. ~ d.ime~5~g 0~ vioe wera as ~0~ CVera11 1ergt:~ 0~ abou~ 3.375 ~:~es; an ~nside dl~ of abalt 0.32 ~r;'~.es at t~.e wi~t se~c~ ar~i 0.25 i~s~es at t'~.e n~ sec.~_~n o~ 'C~.Q
Ve~; b~Y me~ 20 1Y~;~ Oi~ 2.25 i~es; holder 40 1~ C~ a1~t 0.375 in~'~eg; Pieme~ 2~ 1er~L ~ a~t 1.1 ~ C; and. P~ er 5Z 1 a~ 0 . 5 1*e ~:e~al d~cer ~¢ ~:ed to res~ ~e a:Lr ~.a~ ~ 1ivery. Far e~?le, 1;'1e n~t sec'-,~ c~f t'.Q ver~turi can be re~ to aba~t 0.187 2~7~ 3 at a 30a ar~le fc~r c~ eo~ ~n useO o~Pr than d~OEe~, the us~r~ an inhalatian devica si~ilæ to t'~t s~ ~n Fi~s. 1 and 3A was cc~a~
r~c~piersts Gf the }~1 fc r its pres~
n~ ~een ~1 t~ ~y t~e liver. It LS .~la~l t~lat ~1 ti501 LS i~, a Fig. 10 sh~s t~at Dnre ~es ~3~1 was ex~ ~n a 24 h~r df~rioe oî t'.~e preser~ i~tic~ as cc~an~ wit;1l ~es~cr10 Fig., 11 sh~ t~
inhaled ~rtiscl ~s ~re di~ly available ~or ~icn ~n the ur~e at an ~ ~ 7 ~ t the alveolæ epithelium ancl, ~us, els~d sys~ic cir~la~ian ~n a manr~
alm~st e~ival~ to delivery oi~ EI3-cortisoL i~v~nausly. Irl c~T~æ, 'che A ds~7ic~ si~ilar to t~at ~n ~ Figs. 1 ar~ 3A ~as tes~d to dete~mi~
its delivery accuracy.
A con'cainer simila~ ~t ~lawn ~n Figs. 3A ar~l 5 was ~ilLed with aba~t 3.24 ~ o~ finely divid~l material and plaa~ in thie holder ~0 o:e a devic~
s;m-~æ to that shawn in Figs. 1 and 3A. It was nc~t necessary to provide the ~rltainer with a remaveable seal 62 because the finely divided material was dis~arye was }:y h~ vacuLml pump ~th a ~rolu~e a~tely ~al to the human lung. A cansta~ stml~ was used in disp~s~ng to min~m~ze var~atic~n.
we~hed a~, and the residLle o~ finely div~d~ matEr~al det~in~. ~rhis pr~cess was repeat~ t~-five ti~s. qhe ~ainer was vir~ally purgecl w~ each delivery, ar~l the resi~ ~n~ was very cansta~ arxl very small.. rhUs, ve~y aca~rate dose delivery was achieved ~y the use of a d~ica rhis ~;ve~sti~n will ~e ~t}~ I=~stc~ with reference t;o the fo1 examples which are pur~ly exemplary in nature an~ are not meant to l~it the scaDe of the inverTtic~.
~7~13 E~
d~ice si~ilar to t~h~t shc~ igs. 1 and 3A w us~d ~ t~s }~e.
~ollaw~: 100 ~ a~ ~tisol w wei~ ~ a clean c::u~e.. 200 D~ c~
a vial nta~ni~ 0.5ml o~ water ar~l 5.0 ml o~ pi~f~uar. ~tely 6,523,223 ~ts per mir~te~m3 was prepar~, gi~ a speci~ic ætiv~y ~o~
3~ti~1 of 1,279, 063 cs:~l~tsfS~i~/~.
~.
lay@r cqr~matc~ap~.
2 ~
0 d~ns~ t~at o~ otal c~ per min3~ c~ a F~. 11 ~h~ c~ts FOE mi~t~ o:e I~ E3~sol ex~ ~v~ a 24 o~ ~e ~d ~., ~ticn.
a~ c~ai~.
- 24 _
Claims (18)
1. A device for the oral or nasal inhalation of finely divided materials from a removably sealed container which comprises (i) a body member having an air passageway therethrough, one end of the body member being adapted for insertion into the mouth or nose of the user;
(ii) a holder connected to the body member for receiving at least one removably sealed container of finely divided material; and (iii) at least one piercer for piercing the removably sealed container which the sealed container is in the holder, the piercer extending from the body member and into the holder and having a passageway therethrough open to the body member and the holder;
whereby when (a) the removably sealed container is placed in the holder thereby causing the piercer to pierce the sealed container and (b) the container is unsealed, air drawn through the unsealed and pierced container, the piercer, and the body member cooperate to cause finely divided material disposed in the container to be dispensed therefrom.
(ii) a holder connected to the body member for receiving at least one removably sealed container of finely divided material; and (iii) at least one piercer for piercing the removably sealed container which the sealed container is in the holder, the piercer extending from the body member and into the holder and having a passageway therethrough open to the body member and the holder;
whereby when (a) the removably sealed container is placed in the holder thereby causing the piercer to pierce the sealed container and (b) the container is unsealed, air drawn through the unsealed and pierced container, the piercer, and the body member cooperate to cause finely divided material disposed in the container to be dispensed therefrom.
2. A device for the oral or nasal inhalation of finely divided materials form a sealed container which comprises (i) a body member having an air passageway therethrough, one end of the body member adapted for insertion into the mouth or nose of the user;
(ii) a holder connected to the body member for receiving at least one sealed container of finely divided material; and (iii) at least one piercer for piercing through the sealed container while the sealed container is in the holder, the piercer having a passageway therethrough open to the body member and to the holder and extending from the body member through the holder for a distance greater than the dimension of the sealed container to be pierced;
whereby when the sealed container is placed in the holder thereby causing the piercer to pierce through the sealed container and the transfer of the finely divided material form the container to the passageway of the piercer, air drawn through the piercer and the air passageway of the body member cooperate to cause the finely divided material disposed in the piercer to be dispensed therefrom.
(ii) a holder connected to the body member for receiving at least one sealed container of finely divided material; and (iii) at least one piercer for piercing through the sealed container while the sealed container is in the holder, the piercer having a passageway therethrough open to the body member and to the holder and extending from the body member through the holder for a distance greater than the dimension of the sealed container to be pierced;
whereby when the sealed container is placed in the holder thereby causing the piercer to pierce through the sealed container and the transfer of the finely divided material form the container to the passageway of the piercer, air drawn through the piercer and the air passageway of the body member cooperate to cause the finely divided material disposed in the piercer to be dispensed therefrom.
3. The device of claim 2, wherein both the piercer and the sealed container are approximately cylindrical and the container has an inner diameter greater than the outer diameter of the piercer by about 10 to 20 %.
4. A device for the oral or nasal inhalation of finely divided material from a sealed container which comprises (i) a body member having an air passageway therethrough, one end of the body member being adapted for insertion into the mouth or nose of the user;
(ii) a holder for receiving at least one sealed container of finely divided material, the holder being connected to the body member;
(iii) at least one first piercer for piercing the sealed container while in the holder, the first piercer extending into the interior of the holder and having a passageway therethrough open to the body member and the holder;
(iv) at least one second piercer for piercing the sealed container while in the holder, the second piercer extending into the interior of the holder and having an air passageway therethrough, open to the interior and exterior of the holder;
(v) engaging means for causing the first and second piercer, while the sealed container is in the holder, to pierce the sealed container;
whereby when the engaging means causes the first and second piercers to pierce the sealed container while in the holder to create an air passage therethrough, air drawn through the first piercer, the pierced container, the second piercer, and the passageway of the body member cooperate to cause finely divided material disposed in the pierced container to be dispensed therefrom.
(ii) a holder for receiving at least one sealed container of finely divided material, the holder being connected to the body member;
(iii) at least one first piercer for piercing the sealed container while in the holder, the first piercer extending into the interior of the holder and having a passageway therethrough open to the body member and the holder;
(iv) at least one second piercer for piercing the sealed container while in the holder, the second piercer extending into the interior of the holder and having an air passageway therethrough, open to the interior and exterior of the holder;
(v) engaging means for causing the first and second piercer, while the sealed container is in the holder, to pierce the sealed container;
whereby when the engaging means causes the first and second piercers to pierce the sealed container while in the holder to create an air passage therethrough, air drawn through the first piercer, the pierced container, the second piercer, and the passageway of the body member cooperate to cause finely divided material disposed in the pierced container to be dispensed therefrom.
5. A device in accordance with claim 4, further comprising a locating means for positioning the sealed container adjacent the first and second piercers while the sealed container is in the holder.
6. A device in accordance with claims 1, 2, or 4 wherein the air passageway of the body member comprises a venturi or a tube.
7. A device in accordance with claim 6, wherein the first piercer is disposed at or adjacent the smallest diameter of the venturi or the midpoint of the tube.
8. A device in accordance with claims 1, 2, or 4 wherein the piercer comprises a needle.
9. A device in accordance with claim 8, wherein the needle means is sharpened at the piercing end to about a 30 to 45° angle and the rim of the needle opposite the apex is blunted.
10. A device in accordance with claims 1, 2, or 4, wherein the sealed container is a cylindrically shaped cartridge partially filled with finely divided material.
11. A device in accordance with claim 1 or 4, wherein both the sealed containerand the piercer are cylindrical and the end of the container disposed adjacent the body member, while the container is in the holder, has a diameter about 0.005 to 0.015 inches greater than the diameter of the piercer extending from the body member.
12. A device in accordance with claim 11, wherein the diameter of the end of the container disposed adjacent body member while the container is in the holder, increases about 10 to 20% at a distance from said end about equal to the diameter of the piercer extending from the body member.
13. A device in accordance with claim 4, wherein the sealed container is cylindrical and the section of the container extending above the first piercer while the container in the holder has an inner diameter of about 0.035 to 0.180 inches, the first piercer has inner diameter of about 0.01 to 0.15 inches and an outher diameter of about 0.03 to 0.170 inches, and the second piercer hasan inner diameter about 10 to 15% greater than the inner diameter of the first piercer.
14. A device in accordance with claim 4, wherein when the container is in the holder and the engaging means causes the first and second piercers to pierce the container, the first piercer extends into the container for a distance sufficient to hold the piercer extends into the ocntainer for a distance surface of the container.
15. A device in accordance with claim 4, wherein the holder is adapted to receive a disk comprising multiple sealed containers of finely divided material.
16. A device in accordance with claim 4, wherein the dimensions A-D thereof (ref: Fig 6A) are within the ranges:
A About 0.2 to 0.5 inches B About 0.3 to 0.8 inches C About 2 to 4 inches D About 0.5 to 1.5 inches
A About 0.2 to 0.5 inches B About 0.3 to 0.8 inches C About 2 to 4 inches D About 0.5 to 1.5 inches
17. A device in accordance with claims 1, 2, or 4, wherein the sealed container is provided with up to about 25 mg of finely divided material.
18. A device in accordance with claim 1, 2, or 4, wherein the sealed container is provided with about 0.5 to 5 mg of finely divided material.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US738,924 | 1985-05-29 | ||
US07/738,924 US5337740A (en) | 1991-08-01 | 1991-08-01 | Inhalation devices |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2075113A1 true CA2075113A1 (en) | 1993-02-02 |
Family
ID=24970056
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002075113A Abandoned CA2075113A1 (en) | 1991-08-01 | 1992-07-31 | Inhalation devices |
Country Status (15)
Country | Link |
---|---|
US (3) | US5337740A (en) |
EP (1) | EP0525720B1 (en) |
JP (1) | JPH07108316B2 (en) |
AT (1) | ATE146363T1 (en) |
AU (1) | AU665765B2 (en) |
CA (1) | CA2075113A1 (en) |
DE (1) | DE69215994T2 (en) |
DK (1) | DK0525720T3 (en) |
ES (1) | ES2097839T3 (en) |
FI (1) | FI923404A (en) |
GR (1) | GR3022762T3 (en) |
MX (1) | MX9204499A (en) |
NO (1) | NO305852B1 (en) |
NZ (1) | NZ243649A (en) |
ZA (1) | ZA925718B (en) |
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-
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- 1992-07-21 NZ NZ243649A patent/NZ243649A/en unknown
- 1992-07-28 ES ES92112857T patent/ES2097839T3/en not_active Expired - Lifetime
- 1992-07-28 FI FI923404A patent/FI923404A/en not_active Application Discontinuation
- 1992-07-28 DE DE69215994T patent/DE69215994T2/en not_active Expired - Fee Related
- 1992-07-28 AT AT92112857T patent/ATE146363T1/en not_active IP Right Cessation
- 1992-07-28 EP EP92112857A patent/EP0525720B1/en not_active Expired - Lifetime
- 1992-07-28 DK DK92112857.5T patent/DK0525720T3/en active
- 1992-07-30 ZA ZA925718A patent/ZA925718B/en unknown
- 1992-07-30 NO NO923016A patent/NO305852B1/en not_active IP Right Cessation
- 1992-07-31 JP JP4225223A patent/JPH07108316B2/en not_active Expired - Lifetime
- 1992-07-31 MX MX9204499A patent/MX9204499A/en not_active IP Right Cessation
- 1992-07-31 CA CA002075113A patent/CA2075113A1/en not_active Abandoned
-
1994
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-
1996
- 1996-06-24 US US08/672,020 patent/US5715810A/en not_active Expired - Fee Related
-
1997
- 1997-03-07 GR GR970400446T patent/GR3022762T3/en unknown
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FI923404A0 (en) | 1992-07-28 |
ATE146363T1 (en) | 1997-01-15 |
NO305852B1 (en) | 1999-08-09 |
DE69215994D1 (en) | 1997-01-30 |
GR3022762T3 (en) | 1997-06-30 |
DE69215994T2 (en) | 1997-06-26 |
DK0525720T3 (en) | 1997-05-12 |
AU665765B2 (en) | 1996-01-18 |
FI923404A (en) | 1993-02-02 |
NZ243649A (en) | 1995-06-27 |
ES2097839T3 (en) | 1997-04-16 |
ZA925718B (en) | 1994-02-28 |
MX9204499A (en) | 1993-02-01 |
US5715810A (en) | 1998-02-10 |
EP0525720B1 (en) | 1996-12-18 |
US5337740A (en) | 1994-08-16 |
NO923016L (en) | 1993-02-02 |
JPH05192404A (en) | 1993-08-03 |
JPH07108316B2 (en) | 1995-11-22 |
NO923016D0 (en) | 1992-07-30 |
EP0525720A1 (en) | 1993-02-03 |
AU2038492A (en) | 1993-02-04 |
US5529059A (en) | 1996-06-25 |
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EEER | Examination request | ||
FZDE | Discontinued |