Note: Descriptions are shown in the official language in which they were submitted.
1179944
Title of the Invention
CCMPOSITIO~ ~OR T~POR.~.RY SUBSTITUTION 0~ BO~E TISSU~ DEPFCTS
~ield of the In~ention
The present invention relates to medicine and, more spe-
cifically, to a co~lposition for a temporary substitution of
bone tissue defects. The composition is useful both individu-
ally or in combination ~ith an ultrasonic treatment for the
fixation of bone r~g~ents, fixation of bone homotransplantant
at anterior cervical s oncylosis, tenpor-:ry fillin~ of bone
cavities, reccvery of articular surfaces, fi~ation of on-bone
implanted Pctive electrodes for a subsequent electrostimula-
tion of osteo~enesis and the like.
BacXground of the Invention
inown in the art are compositions for a temporary substi-
tution of defects of bone tissue w~ich are based on ~-cyana-
crylates and fillers, e.g. a com~,osition corrlprising ethyl-
- ~ -cyanacrylate and bone chips. (In coll. "Osteosynthesis,
30ne Welding and CuttinF of ~ive Biolo~ical Tissues by Ultr~-
sonic Wave Guides", ~09COW, 1970, p. 12-15, "Grthopedics,
Trawn~tology and rrosthetics", Moscow, 1975, I~o. 10, p.18-23).
In prnctical use of this prior art con,position bone chips
are placed onto a ~one substrate re,~aining after resection,
added with ethyl- ~ -cyanacrylate Pnd under the effect of
ultr~sonic treatrrJent the composition ic transforlned into a
solid con~lomerate temporarily substitutin~ the bone defect.
The composition comprises 50~ by ~eight of bone chips and
50% by weight of ethyl- ~ -cyan-acrylate. 30ne chip~ compri-
se an active co~ponent relative to ethyl- ~ -cyanacrylate and
/
11'79944
cau~es ~n instant curing of the latter. Thi8 does not enable
a preci~e metering of amounts of the components, formation of
a homogeneous composition whlch, in turn, re~ults in instsble
durability characteristics.
Purthermore, bone chips get rapidly impregnated with
ethyl- d~-cyanacrylates ~hich results in the formation Or a
monolithic conglomerate hindering regeneration of bone ti89ue.
Also known in the art i8 a composition containing 70-50~
by weight and 30-50% by ~eight of bone chips with its particles
coated with an envelope of a non-toxic, ~ater~soluble and inso-
luble in ethyl- ~ -cyanacrylate polymer - dextrane (cf. Veden-
kov V.G., Akimova A.Ya., Bukhtiarova G.Y~., Derkach G.M.,
Cys' I.N. "Development of a composition for ultrasonlc welQing
and meltlng-on of bone tissues baYed on modified bone shavings
and ethyl-o~-cyanacrylatet'. Ultra sound and other kinds of
energy in ~urgery. ~oscow, 1974, p.62-66).
Coating of particles of bone chips ~ith an envelope of
a polymer soluble in water and insoluble in ethyl- ~ -cyan~-
crylate hAs made it possble to ensure a more precise dosage of
the components, reduce monolithic chhr~cter of the forming
conglomerate.
However, the use of bone chips in the composition does
not make it pos~ible to obtain a uniform blend after mi~ing
of th~ components. ~or thi~ reason in the cured conglomerate
there can be formed zones with an incr~fised content of bone
chip~ and zones consi~ting essentially of polyethyl- ~ -cya-
nacrylate. The distribution of the component~ in the cured con-
glomerate affects the speed of it~ destruction under the effect
1179944
of the arganism media which, in turn, ca~ slo~-down the speed
of regeneration of bone tis~ue. Therefore, in the use Or modi-
fted bone chips a~ 8 filler it i8 impo~sible to obtain stable
reproducible re~ults as regards the ~peed o~ biodestruction
of the conglomerate.
The disadvantage of the above-mentioned composition also
resides in that bone chips compri~e an e~pensive product not
suitable for stand~rdization. Furthermore, the use of ethyl-
- ~ -cyanacrylste in this compo~ition re~ults i~ the ~ormation
o~ a conglomerate resi~tant to the effect of the organism me-
dia and it~ biodestruction proceeds but 810wly, wherefore the
conglomerate hinders regeneration of the newly formed bone tl-
ssue. In view of the above-listed disadvantages thie compo~i-
tion hQs not found any suitable application in practical medi-
cine.
Summsry Or the Invention
It i~ an object Or the present invention to provide ~
composition for Q temporary substitution of bone tissue defects
~hich would be useful in mediacl practice and enabling reduced
time of biodestruction of the cured conglomerate, thus provld-
ing favourable condition~ for regeneration of bone tissue and
reducing the time of treatment and rehabilitation of patients.
This object i~ Accomplished by that the compo~ition for
a temporary ~ubstitution of bone ti~ue defect~ on the basls
of ~ -cyanacrylic acid e~ters and a filler, according to the
pre~ent invention, contains a powder-11lce filler - a salt of
Galcium of an organic or inorganic acid with a particle 8~ ze
of from 0.01 to 0.5 mm, the components being pre~ent in the
--4--
1179944
following proportions, per cent by ~eight: -
~-cyanscrylic acid esters 60 to 40
calcium ~alt of organic or inorganic
acid with a partlcle size of 0.01-0.5 mm 40 to 60.
As calclum ~alts of organic or inorganic acids the compo-
~ition according to the present invention caD incorporate cal-
cium carbonate, calcium gluconste, calcium chloride, calcium
phosphate, calcium citrate. It i8 preferable that the compo~i-
tion would cont~in calcium gluconate or calcium carbonate. To
impart a predetermined physiological effect to the prepara-
tion, it should be a~ded with regeneration stimul~nte and anti-
~eptics.
The r,reparation according to the preYent invention prefe-
rably contains, as a regeneration stimulant, 4-uracylcarboxy-
lic acid (orotic acid) or its derivatives in an amount of from
10 to 30% by weight.
A~ the anti~eptic the composition accordin~ to the present
invention preferably incorporate~ 1,4-di-N-oxy ~,3-dlhydro~y-
methylquino~aline or 1,4-di-N-oxy 2,3-d;aceto~ymethylqulno~a-
line in an amo~nt of from 10 to 3~0 by weight.
A~ the composition base intended for the provisi~n of
adjusted time limits of biodestruction Or the cured conglomera-
te, it i8 preferred to use a nixture of ethyl- J~-cyanacrylate
and etho~yethyl- ~-cyanacrylate, the componentQ being pre6cnt
in the following proportions, per cent by weight:
ethyl- ~ -cyanacrylate 80 to 95
etho~yethyl- ~cyanacrylate 20 to 5.
1179944
Detsiled De~cription of the Invention
The composition i8 prepared directl~ before u~e by mi~ing
the compos~tion component~ at room temperature in a polyethy-
lene or fluoropla~t~c vessel. After l~ixing Or the component~
paste-like mas~ 19 formed which ha~ sdherence to the bone
ti~ue. The life time of the compo~ition ran&e~ ~ithin 5 to
30 minutes depending on the employed calcium salt and propor-
tion~ of the components.
The p&ste-like m~ss i8 applied onto a preliminarily dried
surface of the bone tissue. To accelerate the process of curing
of the composition u~e can be n,ade of an ultrasonlc treatment
(amplitude ~0-55Jum, frequency 26.5 kHz, treatrnent time 30-60
3econds ) .
Curing o~ the composition by the effect of ultra sound
occurs within 1-2 minutes, without ultrasonic treatment - with-
in 5 to 30 minutes. The u~e of calc~um ~alt in the composition
according to the present ~nvention as a filler ~laXea it possib
le to pro~uce ~ uniform mixture after blending of the conlpo-
nents uhich, in turn, en~ures reproducible dats as regards
the ~l~ed of b~odestruction of the cured conglomerate.
The u~e of the composition containing a calcium salt and
a mixture of ethyl- and etho~yethyl- ~ -cyan&crylate makes it
possible to reduce the duration of biode~truction of the cured
con~lomerate by 0.8-2 times as co~pared with the co~iposition
incorporating bone chip~ 6nd ethyl~ cyanacrylste.
To lncrease hydrophillc power of the composition, partic-
les of the salt of calcium can be coated with envelopes of R
non-toxic polymer soluble in ~ater and in~oluble in ~ cyana-
11799~4
crylates.
As the ~alts Or calcium use can be m de of different orga-
nic and inorganic c81cium salts such as calcium carbonste,
calcium chloride, calcium phosphate, calcium citrate, calclum
gluconate and the like.
hs the regeneration stimulants use i8 made Or 4-uracyl-
carbo~ylic scid, potassium salt of 4-uracylcsrbo~ylic acid and
the like. As antiseptics use c~n be made of antibiotics or
such compounds a~ 1,4-di-~-oxide 2,3-dihydroxymethylquino~a-
line, 1,4-di-N-o~y 2,3-diaceto~ymethylquino~aline. The regene-
ration stimulants and antiseptic~ are introdiced in an ~mount
ranging from 10 to 30% by weight.
The composltlon according to the present invention has no
toxic e~fect, ensures a lasting evolution of the regeneration
stimulants into thetrauma zone, ret~inc bactericidsl proper-
ties within 2-3 ~eek~ after the operation and provides no
hindering effect on regeneration of the bone tissue.
The compo~ition for a temporary substitution of bone tis-
sue defects h~s been tested in clinics on 200 patients. The
composition is prepared right betore use and applied onto pre-
liminarily drled surface of a bone ti~aue. The composition
has thus ~een tested.
~ or filling of bone cavities in radical operations on
patients suffering from chronical osteomyelitis including
~houlder osteomyelitis, femor~l osteomyelltis, tibial osteo-
myelitis, i~hiatic osteomyelitis. In all c~se~ there i~ ob-
serYed nealiDg of--wounds by primary e~tension; no compl~cations
associated with the use of the composition according to the
~179944
pre~ent invention are observed.
The use of the composition according to the present in
vention make~ it possible to avold drainaæe.
In reconstruction operations of ~rongly consolidated frac-
tures, rheumatic polyarthritis, for fixation of bone fragment~
of forearm, peroneal bone, shinbone, collar bone, fixation of
bone transplantant~ ~ith the use of the composition of this
invention heali~g occured without complications. In none of the
cases a~y secondar~ di~placement ~as observed.
In fi~ation of bone grafts to prevent micro- and macro-
shiftings in reconstruction steps of osteoplastic operations
of chronical otitis med~a, non-purulent disease of middle ear,
chronical diseases of nasal sccessory sinuses, ma~i,llary sinus
cyst, ethmoidal sinus osteoma with the use of the compo~ition
according to the present invention no complications were ob-
served. The use of the composition made it possib1e to reduce
the duration of ~tay of the patients in the hospital by 4-6
days, as uell as to ensure a strict restoration of anatomic
reliefs which is e~pecially important froln both functional and
cosmetic standpoint. The composition accor~ing to the pre~ent
lnvention ha~ been also tested for fixation of on-bone implan-
ted electrodes for carrying out electrostimulation, as well
as for fixation of ~one homotransplantant at a~terior cervical
spondyoledosis.
The use of the composition acsording to tbe present in-
vention has made it possible to avoid an externsl fixation of
the cer~ical part of spin~l column thu~ ~llowing an early ac-
tivization o~ patients. The dur&tion of ~tsy of the patients
~79944
~n hospitEl W2S reduced b~ 2 wee~s~ No shiftings and compli~
cations due to the use of the composition were observed.
~ or a better understan~ing of the p~esent inve~tion some
specific examples illustratinO the co~posi~,ion for a tempora~
r~ subs~itution of defects of bone tissue are ~iven hereln~
belo~.
Ji.ample
A composition for a temporary sub~,titution of' bone tis-
sue defects consists of the follo~ing componentC~ per cent
by ~,eight:
cc~lcium carbona~e ~ith a par~icle
size of from 0.01 ~o 0.05 mm 50
ethyl~ ~ ~cyc?n2crylate 45
ethoxyethyl~ ~ -cyanacrylate 5
~ sterile ~eighed portion enc2psulated in de}~rane, m-'x~
ed ~ith ~ -cyan~crylic ~cid esters till the formation of a
paste-like mass. ~he cohesion strength of the cured conglome~
rate determined on the instrument Dins~et Dis (ultimate bend-
:ng strength) is 200 to 250 kg/cm . ~he sc~mple weight decre~se
after the residence in ~ater at the ter~perature of 37C for
28 d~ys is 8,~ he composition is in-tc-n~ed for fi~c?tion of
bone fragments~ bone transplantant, securing of on-bone imp~
lanted active electro~es.
~ -am~le 2
~ co~.,.,os-tion ~or a ter~pora y su'~stitution of bone tis~
sue defects con~ists of ~he follG~ing co-~Gnents, per cent
b~- weight:
calcium gluconate with a particle size
of from 0~05 to 0.2 mm 60
1~7994~
.
ethyl- ~ -cyanscrylate 3~
etho~yethyl- ~ -cyanacrylate 8.
A ~terile weighed portion of calcium gluconate i8 mi~-
ed with ~-cyanacrylic acid ester3 to obtain a paste-like
ma~. The cohesion ~trength of the cured conglomerate deter-
mined on the in~trument Dinstat Dis (ultimate bending strength
i~ 230-250 kg/cm2. The sample weight decr~ase after residence
in water at the temperature of 37C for 28 days i~ ~0%. The
composition ~s inten~ed for fixation of bone framents, bone
transplantant~, securing of on bone implanted acti~e elect-
rodes, restorstion of articular surfaces.
Example 3
A composition for a temporary ~ub~titution of bone tis-
~ue defects consist~ of the following components, per cent by
weight:
disubstituted calcium orthophosphate 60
ethyl- ~ -cyanacrylate 40.
The composition i8 prepared follo.~.in~ the procedure si-
milar to that described in Example 1 hereinbefore. The cohe-
sion strength RS determined on the in~trument Dinstat Dls
~ultimate bending strength) is 250-280 kg/cm2. The sam~le
weight decrease after residence in water at the temperature
of 37C ~or 28 days i~ 5%. The compo~ition ls intended ior
fixation of on-bone implanted actiYe electrodes, restorat~on
of ~rticular surfaces.
Example 4
A compo~it~on for a temporary ~ubstitution of bone tis-
sue defect~ Gonsi~ts of the ~ollowing cimponents, per cent
117g94~ '
b~ weight:
calcium gluconate 20
potassium sHlt of 4-urscyl-
carbo~ylic ac~d . 20
ethyl- d -cganacrylate 40
ethoxyethyl- ~ -cyanacrylate 10.
The compo~itlon i8 prep~red in a msnner simllar to that
described in E~ample~ 1 and 2. The conhesion strength of the
cured.conglo~erate determined on the lnstrument Din~tat-Di~
is 200 to 220 kg/cm2. The sample u-eight decrease after re~i-
dence ln water for 28 dPya st the temperature of 37C is 20%.
The composition i8 intended ror fixation of electrodes, re~-
toration of articular surraces~ fi~ation of bone homotrans-
plantants in the case of anterior cervlc~l spondyoledo~ 8.
Example 5
- A compo~ition for a temporar~ ~ub~titution of bone ti8-
sue defects con8i8t8 of the ~-ollowing components, per cent by
welght:
calcium carbonate 30
1,4-dl-N-oxy 2,3-diacetoxymethyl-
quino~aline 10
ethyl- ~ -cyan~crylate 60~
'l'he composition i9 prepared in a manner similar to that
of ~ample~ 1 and 2. The cohesion strength of the cured conglo-
merate a~ determined on the ~n~trument D~nstat-D1s (ultimate
ben~ing strength) is 250-280 kg/cm2. The samp weight decre-
ase sfter re~idence iD ~ater ~t the temperature of 37C for
28 days i8 15%. The compo~ition is i~tended for fixati~n of
--11--
1~79944
bone transplantants, filli~g o~ post-operation bone csvitie~
with a volume of up to 2 cm3.
Example 6
A compo~ition for a temporary substitution of bone tis-
sue defects consists of the following components, per cent by
~ei~ht:
calcium ~luconate 30
4-uracylcarbo~yl$c acid 8
kanamycin (antlbiotic produced by
Actinom~ce~ kanamyceticus) 12
ethyl- ~ -cysnacrylate 40
ethoxyethyl- ~/-cyanacrylate 10.
The composition is prepared in a manner similar to that
of Exsmples 1 and 2. The co_hesion strength of the cured con-
glomerate determined on the in~trument Din~tat-Dis (ultimate
bending strength) ia 200-220 kg/cm2. The ~nple weight dec-
reaae after reaidence in water at the temperature of 37C for
28 day~ is 23%~
The compo~ition is intended for filling post-operation
bone cav-ities, ~ixation of bo~e fragments.
Ex~mple 7
A composition for a temporary substitutlon of bone tis-
sue defects cons~sts of the following component~, per cent
by ~elght:
calcium gluconate 30
1,4-di-~-oxy 2~3-dihydroxymethyl-
~uino~aline 12
4-uracylcsrbo~ylic ac~d 8
~1799~4
ethyl- ~ -cyanacrylate 48
ethoxyethyl- ~ -cyanacrylate 2.
The composition i~ prepared ln A manner Qimllar to t~at
deacribed in ~xamples 1 and 2. The cohesion strength of the
cured conglomerate as determined on the instrument Dinstat-
Dis (ultimate bending strength) i9 200 to 230 kg/cm2. The
ple weight decrease after re~idence in water at the tem-
perature of 37C for 28 days i~ 2~%.
The compo~ition is intended for fi~tion of bone homo-
transplantants, filling of post-operation bone cavities in
radicsl operations on patient~ suffering ~rom chronical osteo-
myelitis and the llke. The use of the composition in reconst-
ruction stages of osteoplastlc operations in otolaryngology
has enabled a shortened duratlon of stay of the patients in
the hospitsl by 4-6 days.
~xample 8 (comparative)
composition for a temporary ~ubstitution of bone t~-
~ue defect~ c~n~i~ts of the following component~, ~er cent
by weight:
modifled bone chips 50
ethyl- ~ -cyanacrylnte 50.
The cohe~ion ~trength of the composition detel~ined on the
instrument Dinstat-Di~ (ultimate bend-ng ~trength) ia varied
within the range of from 100 to 300 kg~cm2. The ~ample weight
1O~8 after residence in water at the t.mperature of 37~C for
28 day~ varies from 2 to 15~D (at the con~tant proportions of
the co~lponents~.
