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International Journal of BioMaterials Science and Engineering 2015 2(1) 1-4
Published online May 30 2015 (httpwwwopenscienceonlinecomjournalbiom)
Transport Properties of Some Forms of Hydroxyapatite
E A Bogdanova1 N A Sabirzyanov
1 T G Khonina
2
1Federal State government-Financed Research Institution Institute of Solid State Chemistry of the Ural Branch of the Russian Academy of
Sciences Ekaterinburg Russia 2Federal State government-Financed Research Institution IYa Postovsky Institute of Organic Synthesis Ural Brunch of Russian Academy of
Sciences Ekaterinburg Russia
Email address
sabirzyanovihimuranru (N A Sabirzyanov)
To cite this article E A Bogdanova N A Sabirzyanov T G Khonina Transport Properties of Some Forms of Hydroxyapatite International Journal of
BioMaterials Science and Engineering Vol 2 No 1 2015 pp 1-4
Abstract
Transmucosal permeability of different forms of hydroxyapatite (suspension colloidal solution) has been investigated Colloidal
hydroxyapatite was found to exhibit higher penetrating ability The influence of silicon glycerolates on the transport properties of
hydroxyapatite was studied and their prominent role was determined
Keywords
Hydroxyapatite Silicon-Containing Glycerohydrogels Transmucosal Permeability
1 Introduction
Along with drugs for systemic effect the drugs for local
application are often used for the treatment of various
inflammatory diseases of skin soft tissues and mucous
membranes In some cases their use is more preferable since
the probability of side effects is reduced The introduction of
medicinal substances through the skin and mucous
membranes is widely used in different fields of medicine -
dermatology dentistry ophthalmology gynecology
cardiology etc - to exert local and resorptive action [1minus3]
To affect an organism a medicine as a rule should pass
through a number of biological membranes The onset time
and the strength of the effect depend on the speed and
completeness of resorption of medicine from the place of
introduction ie on its biological availability During
absorption the medicine passes through skin and mucous
membranes capillary walls cellular and subcellular
structures
The transport of drugs through biological membranes
depends on the nature of sub-stance its physical and chemical
properties and can be passive or active Passive transport takes
place along the concentration gradient without any carrier and
without energy consumption The drugs dissolve in the
membrane lipid basis and pass through it due to simple
diffusion Passive simple diffusion and filtration are the main
mechanisms of absorption of drugs regardless of the way of
their introduction
It is known that silicon glycerolates and glycerohydrogels
on their basis are a perspective biologically active ointment
base for pharmaceutical compositions of local and external
action having a wide range of clinical applications They show
high transport properties with respect to various medicinal and
biologically active additives which allow one to increase the
efficiency of pharmaceutical compositions and to lower the
portion of active additives in them [4] However the
mechanism by which the silicon-containing glycerohydrogels
provide transport through biological membranes has not been
studied comprehensively
Earlier we have obtained combined
calcium-phosphorus-siliceous hydrogels on the basis of
silicon glycerolates and hydroxyapatite (HAP) in various
forms (suspension colloidal solution) possessing wound
healing and osteoplastic effects and approved as agents for
treatment of inflammatory periodontal disease [5minus9] Thanks
to high transport properties of siliceous hydrogels based on
silicon glycerolates HAP provides efficient curing of tooth
enamel microcracks leading to positive therapeutic effect
Since one of the factors determining substance transport
through biological membranes is the aggregate state of
substance it is interesting to investigate the transmucosal
2 E A Bogdanova et al Transport Properties of Some Forms of Hydroxyapatite
properties of HAP having different degrees of dispersion
(suspension colloidal solution) and to estimate the effect of
silicon glycerolates on the permeability of HAP through the
mucous membrane
2 Material and Methods
The transmucosal permeability of hydroxyapatite was
studied by measuring the diffusion of a substance through a
natural biological membrane fixed in a diffusion chamber (in
vitro) in the presence of transcutaneous conductors
Fig 1 The diffusion chambers for studying the transmucosal permeability of
HAP 1 ndash non-assembled 2 ndash during experiment (a minus examined composition
b minus biological membrane c minus isotonic solution)
The silicon glycerolate Si(C3H7O3)46C3H8O3 [4] with
initial concentration in isotonic solution 10 wt was used as
a transcutaneous conductor Different forms (colloidal
solution suspension) of high-purity HAP developed earlier
[10] were used The initial concentration of HAP in isotonic
solution was 1 wt Intact samples of mucous membrane of
small intestine of a calf were used as a biological membrane
Specially designed diffusion chambers were used in the
experiment (Fig1) The flaps (1cm2) of mucous membrane of
small intestine whose epithelium is turned towards the initial
solution were tightly fixed in the diffusion chambers between
two cells with a volume of 75 ml each one of the cells was
filled with the examined solution and the other cell - with
isotonic (09 NaCl) solution The experiments were carried
out in 4 series (3 parallels in each series) at a temperature of
30plusmn2degС for 24 h
The first series served as a reference the examined
composition was a 10 solution of silicon glycerolate
Si(C3H7O3)46C3H8O3 in isotonic solution In the second series
of experiments the composition containing ca 1 wt HAP
in the form of colloidal solution (the calculated content of
Ca=59841 mgl and the experimental content of Ca=4700
mgl correspond to colloidal solution with 22 wt
concentration of the main substance) and isotonic solution was
studied In the third series of experiments we examined a
composition containing a 10 solution of silicon glycerolate
Si(C3H7O3)46C3H8O3 and 1 HAP (suspension) in isotonic
solution In the fourth series a composition containing a 10
solution of silicon glycerolate Si(C3H7O3)46C3H8O3 ca1
of HAP in the form of colloidal solution and isotonic solution
was studied The examined compositions are presented in
table 1
After 24 h exposition the solutions in each cell were
analyzed for the contents of cal-cium and silicon
corresponding to the concentrations of HAP and silicon
glycerolates The concentration of calcium was determined by
the mass spectrometry method with inductively coupled
plasma (ISP-MS Spectromass 2000) and the concentration of
silicon - by the atomic-emission spectrophotometry method
(AESA) on a Joben Yvon spectrophotometer (JY 48) The
experimental data are listed in table 2
Table 1 The composition of mixtures
Composition
Concentration wt
Si(C3H7O3)46C3H8O3 HAP
Isotonic solution (NaCl 09) Colloidal form Suspension
1 10 minus minus the rest
2 minus asymp1 minus the rest
3 10 minus 1 the rest
4 10 asymp1 minus the rest
International Journal of BioMaterials Science and Engineering 2015 2(1) 1-4 3
Table 2 The content of calcium and silicon according to ISP-MS and AESA
Composition Parallel
Content of elements mgl
Ca Si
Initial Passed through
the membrane Residue Initial
Passed through
the membrane Residue
1
1
sim40
370 280
29720
430 1488
2 240 390 170 1870
3 160 200 lt05 500
2
1
313325
330 18250
minus
lt05 lt05
2 330 15600 lt05 lt05
3 350 15000 lt05 lt05
3
1
398937
340 16000
29720
lt05 920
2 400 21000 lt05 1090
3 400 18000 10 1300
4
1
313325
370 12750
29720
lt05 710
2 290 11350 lt05 700
3 350 14000 lt05 710
3 Results and Discussion
It was established that calcium in the examined
compositions practically does not penetrate through the
mucous membrane into the solutions contained in the
receiving cells The insignificant amounts of calcium found in
the cells correspond to the concentration of calcium in isotonic
solution At the same time in all the cases the initial
concentration of calcium decreased essentially pointing to
penetration of HAP into the mucous membrane (Table 3)
Table 3 Residual concentration of calcium in the studied compositions
Composition Residual concentration of Ca
2 5197
3 4596
4 4053
As can be seen from table 3 in the absence of
transcutaneous conductors the colloidal solution of HAP
shows rather high penetrating activity in comparison with
crystal forms The greatest degree of diffusion of colloidal
HAP is provided by silicon glycerolates as evidenced by the
smallest residual concentration of calcium in the initial
solution A rather high absorbing ability of the mucous
membrane with respect to calcium is noted (Fig 2)
Fig 2 The amount of calcium passed into the mucous membrane 1 ndash HAP
(colloidal) 2 ndash HAP (suspension) + silicon glycerolates 3 ndash HAP (colloidal)
+ silicon glycerolates
The results obtained testify that the most active
transcutaneous conductors are silicon glycerolates In
composition 1 only ca 2 of the initial amount of silicon
diffuse through the membrane while ca 25 of silicon left in
the initial solution allow us to conclude that the main body of
calcium remains in the mucous membrane
In case of joint presence of silicon glycerolates and HAP
silicon like calcium does not pass through the membrane
which can also testify to the interaction between them
Since the interaction of HAP with organic substances takes
place by the surface adsorption type where the main
absorbent elements of HAP are calcium ions and phosphate
ions the ability of silicon glycerolates to promote HAP
diffusion is likely to be due to the appearance of CaminusOminusSi
PminusOminusSi and CaminusOminusC coordination bonds between them The
absence of chemical interaction giving rise to covalent bonds
has been proved experimentally The IR-spectra of the
compositions obtained during the interaction of colloid HAP
and silicon glycerolates taken in equimolar ratios at different
temperatures (20 and 60degC) did not reveal any visible changes
(displacement of characteristic frequencies and appearance of
new absorption bands) in comparison with the spectra of the
initial materials [11]
4 Conclusion
It was established that the biological activity of HAP
depends substantially on the size of particles (or grains) and is
more pronounced when the dispersion of a substance is higher
The research performed showed that colloidal HAP exhibits
higher penetrating ability in tissues than its crystal forms The
presence of silicon glycerolates promotes penetration of HAP
into the mucous membrane
Note that the presented results cannot be automatically
extrapolated to human organism as they are obtained in in
vitro experiments In a living organism the speed of
penetration of substances through a biological membrane
(skin mucous membrane) depends not only on its structure as
a barrier but also on its physiological state
The studies performed allow us to recommend HAP for
further research aimed at its practical application both as an
4 E A Bogdanova et al Transport Properties of Some Forms of Hydroxyapatite
independent medicine and as a component of pharmaceutical
compositions with improved regeneration of bone tissues and
enhanced therapeutic action
References
[1] Janick S Gabiga H Untersuchung der in vitro ndash freigabegeschwindigkeit von Isosorbiddinitrat aus einem transdermalen terapeutischen Membransystem Pharmazie 1989 44(1) 68
[2] Rajech D Gandi and Joseph R Robinson Bioadhesion in drug delivery Indian Pharm Sci 1988 50(3) 145-152
[3] Ziegenmeyer J TTS Transdermale Applikation von Arzneistoffen Pharm Ztg 1999 134(2) 24-30
[4] T G Khonina LP Larionov Rusinov GL et alrdquoSilicon glycerates possessing transcutaneous conductivity of drugs and glycerohydrogels based thereonrdquo RF Patent 2255939 published 10 July 2005 [in Russian]
[5] Sabirzyanov NA Khonina TG Evdokimova KV et al New materials for medicine Ekaterinburg UrO RAN 2006 pp 100-107 [in Russian]
[6] NА Sabirzyanov LP Larionov SP Yatsenko et alrdquoMethod for production of wound healing and osteoplastic agentrdquo RF Patent 2314107 published 10 January 2008 [in Russian]
[7] NА Sabirzyanov T G Khonina G I Ron SP Yatsenko et alrdquoAgent for treatment of inflammatory diseases of periodontiumrdquo RF Patent 2296556 published 10 April 2007 [in Russian]
[8] N G Sarkisyan G I Ron N A Sabirzyanov E A Bogdanova et alrdquoMethod for treatment of periodontitisrdquo RF Patent 2330645 published 10 August 2008 [in Russian]
[9] Sarkisyan N G Ron G I Khonina T G Bogdanova E A Sabirzyanov N A Experience of using drug formulations for treatment of periodontitis Uralskii meditsinskii zhurnal (Ural medical journal 2008 45(5) 104-106 [in Russian]
[10] SP Yatsenko NА Sabirzyanov lsquoMethod for production of hydroxyapatitersquo RF patent 2104924 published 20 February 1998 [in Russian]
[11] Е А Bogdanova lsquoThe physicochemical properties of bioactive composite materials based on calcium phosphates and organic silicon compoundsrsquo PhD thesis Federal State government-financed research institution Institute of Solid State Chemistry of the Ural Branch of the Russian Academy of Sciences Ekaterinburg Russia 2012 130 p [in Russian]
2 E A Bogdanova et al Transport Properties of Some Forms of Hydroxyapatite
properties of HAP having different degrees of dispersion
(suspension colloidal solution) and to estimate the effect of
silicon glycerolates on the permeability of HAP through the
mucous membrane
2 Material and Methods
The transmucosal permeability of hydroxyapatite was
studied by measuring the diffusion of a substance through a
natural biological membrane fixed in a diffusion chamber (in
vitro) in the presence of transcutaneous conductors
Fig 1 The diffusion chambers for studying the transmucosal permeability of
HAP 1 ndash non-assembled 2 ndash during experiment (a minus examined composition
b minus biological membrane c minus isotonic solution)
The silicon glycerolate Si(C3H7O3)46C3H8O3 [4] with
initial concentration in isotonic solution 10 wt was used as
a transcutaneous conductor Different forms (colloidal
solution suspension) of high-purity HAP developed earlier
[10] were used The initial concentration of HAP in isotonic
solution was 1 wt Intact samples of mucous membrane of
small intestine of a calf were used as a biological membrane
Specially designed diffusion chambers were used in the
experiment (Fig1) The flaps (1cm2) of mucous membrane of
small intestine whose epithelium is turned towards the initial
solution were tightly fixed in the diffusion chambers between
two cells with a volume of 75 ml each one of the cells was
filled with the examined solution and the other cell - with
isotonic (09 NaCl) solution The experiments were carried
out in 4 series (3 parallels in each series) at a temperature of
30plusmn2degС for 24 h
The first series served as a reference the examined
composition was a 10 solution of silicon glycerolate
Si(C3H7O3)46C3H8O3 in isotonic solution In the second series
of experiments the composition containing ca 1 wt HAP
in the form of colloidal solution (the calculated content of
Ca=59841 mgl and the experimental content of Ca=4700
mgl correspond to colloidal solution with 22 wt
concentration of the main substance) and isotonic solution was
studied In the third series of experiments we examined a
composition containing a 10 solution of silicon glycerolate
Si(C3H7O3)46C3H8O3 and 1 HAP (suspension) in isotonic
solution In the fourth series a composition containing a 10
solution of silicon glycerolate Si(C3H7O3)46C3H8O3 ca1
of HAP in the form of colloidal solution and isotonic solution
was studied The examined compositions are presented in
table 1
After 24 h exposition the solutions in each cell were
analyzed for the contents of cal-cium and silicon
corresponding to the concentrations of HAP and silicon
glycerolates The concentration of calcium was determined by
the mass spectrometry method with inductively coupled
plasma (ISP-MS Spectromass 2000) and the concentration of
silicon - by the atomic-emission spectrophotometry method
(AESA) on a Joben Yvon spectrophotometer (JY 48) The
experimental data are listed in table 2
Table 1 The composition of mixtures
Composition
Concentration wt
Si(C3H7O3)46C3H8O3 HAP
Isotonic solution (NaCl 09) Colloidal form Suspension
1 10 minus minus the rest
2 minus asymp1 minus the rest
3 10 minus 1 the rest
4 10 asymp1 minus the rest
International Journal of BioMaterials Science and Engineering 2015 2(1) 1-4 3
Table 2 The content of calcium and silicon according to ISP-MS and AESA
Composition Parallel
Content of elements mgl
Ca Si
Initial Passed through
the membrane Residue Initial
Passed through
the membrane Residue
1
1
sim40
370 280
29720
430 1488
2 240 390 170 1870
3 160 200 lt05 500
2
1
313325
330 18250
minus
lt05 lt05
2 330 15600 lt05 lt05
3 350 15000 lt05 lt05
3
1
398937
340 16000
29720
lt05 920
2 400 21000 lt05 1090
3 400 18000 10 1300
4
1
313325
370 12750
29720
lt05 710
2 290 11350 lt05 700
3 350 14000 lt05 710
3 Results and Discussion
It was established that calcium in the examined
compositions practically does not penetrate through the
mucous membrane into the solutions contained in the
receiving cells The insignificant amounts of calcium found in
the cells correspond to the concentration of calcium in isotonic
solution At the same time in all the cases the initial
concentration of calcium decreased essentially pointing to
penetration of HAP into the mucous membrane (Table 3)
Table 3 Residual concentration of calcium in the studied compositions
Composition Residual concentration of Ca
2 5197
3 4596
4 4053
As can be seen from table 3 in the absence of
transcutaneous conductors the colloidal solution of HAP
shows rather high penetrating activity in comparison with
crystal forms The greatest degree of diffusion of colloidal
HAP is provided by silicon glycerolates as evidenced by the
smallest residual concentration of calcium in the initial
solution A rather high absorbing ability of the mucous
membrane with respect to calcium is noted (Fig 2)
Fig 2 The amount of calcium passed into the mucous membrane 1 ndash HAP
(colloidal) 2 ndash HAP (suspension) + silicon glycerolates 3 ndash HAP (colloidal)
+ silicon glycerolates
The results obtained testify that the most active
transcutaneous conductors are silicon glycerolates In
composition 1 only ca 2 of the initial amount of silicon
diffuse through the membrane while ca 25 of silicon left in
the initial solution allow us to conclude that the main body of
calcium remains in the mucous membrane
In case of joint presence of silicon glycerolates and HAP
silicon like calcium does not pass through the membrane
which can also testify to the interaction between them
Since the interaction of HAP with organic substances takes
place by the surface adsorption type where the main
absorbent elements of HAP are calcium ions and phosphate
ions the ability of silicon glycerolates to promote HAP
diffusion is likely to be due to the appearance of CaminusOminusSi
PminusOminusSi and CaminusOminusC coordination bonds between them The
absence of chemical interaction giving rise to covalent bonds
has been proved experimentally The IR-spectra of the
compositions obtained during the interaction of colloid HAP
and silicon glycerolates taken in equimolar ratios at different
temperatures (20 and 60degC) did not reveal any visible changes
(displacement of characteristic frequencies and appearance of
new absorption bands) in comparison with the spectra of the
initial materials [11]
4 Conclusion
It was established that the biological activity of HAP
depends substantially on the size of particles (or grains) and is
more pronounced when the dispersion of a substance is higher
The research performed showed that colloidal HAP exhibits
higher penetrating ability in tissues than its crystal forms The
presence of silicon glycerolates promotes penetration of HAP
into the mucous membrane
Note that the presented results cannot be automatically
extrapolated to human organism as they are obtained in in
vitro experiments In a living organism the speed of
penetration of substances through a biological membrane
(skin mucous membrane) depends not only on its structure as
a barrier but also on its physiological state
The studies performed allow us to recommend HAP for
further research aimed at its practical application both as an
4 E A Bogdanova et al Transport Properties of Some Forms of Hydroxyapatite
independent medicine and as a component of pharmaceutical
compositions with improved regeneration of bone tissues and
enhanced therapeutic action
References
[1] Janick S Gabiga H Untersuchung der in vitro ndash freigabegeschwindigkeit von Isosorbiddinitrat aus einem transdermalen terapeutischen Membransystem Pharmazie 1989 44(1) 68
[2] Rajech D Gandi and Joseph R Robinson Bioadhesion in drug delivery Indian Pharm Sci 1988 50(3) 145-152
[3] Ziegenmeyer J TTS Transdermale Applikation von Arzneistoffen Pharm Ztg 1999 134(2) 24-30
[4] T G Khonina LP Larionov Rusinov GL et alrdquoSilicon glycerates possessing transcutaneous conductivity of drugs and glycerohydrogels based thereonrdquo RF Patent 2255939 published 10 July 2005 [in Russian]
[5] Sabirzyanov NA Khonina TG Evdokimova KV et al New materials for medicine Ekaterinburg UrO RAN 2006 pp 100-107 [in Russian]
[6] NА Sabirzyanov LP Larionov SP Yatsenko et alrdquoMethod for production of wound healing and osteoplastic agentrdquo RF Patent 2314107 published 10 January 2008 [in Russian]
[7] NА Sabirzyanov T G Khonina G I Ron SP Yatsenko et alrdquoAgent for treatment of inflammatory diseases of periodontiumrdquo RF Patent 2296556 published 10 April 2007 [in Russian]
[8] N G Sarkisyan G I Ron N A Sabirzyanov E A Bogdanova et alrdquoMethod for treatment of periodontitisrdquo RF Patent 2330645 published 10 August 2008 [in Russian]
[9] Sarkisyan N G Ron G I Khonina T G Bogdanova E A Sabirzyanov N A Experience of using drug formulations for treatment of periodontitis Uralskii meditsinskii zhurnal (Ural medical journal 2008 45(5) 104-106 [in Russian]
[10] SP Yatsenko NА Sabirzyanov lsquoMethod for production of hydroxyapatitersquo RF patent 2104924 published 20 February 1998 [in Russian]
[11] Е А Bogdanova lsquoThe physicochemical properties of bioactive composite materials based on calcium phosphates and organic silicon compoundsrsquo PhD thesis Federal State government-financed research institution Institute of Solid State Chemistry of the Ural Branch of the Russian Academy of Sciences Ekaterinburg Russia 2012 130 p [in Russian]
International Journal of BioMaterials Science and Engineering 2015 2(1) 1-4 3
Table 2 The content of calcium and silicon according to ISP-MS and AESA
Composition Parallel
Content of elements mgl
Ca Si
Initial Passed through
the membrane Residue Initial
Passed through
the membrane Residue
1
1
sim40
370 280
29720
430 1488
2 240 390 170 1870
3 160 200 lt05 500
2
1
313325
330 18250
minus
lt05 lt05
2 330 15600 lt05 lt05
3 350 15000 lt05 lt05
3
1
398937
340 16000
29720
lt05 920
2 400 21000 lt05 1090
3 400 18000 10 1300
4
1
313325
370 12750
29720
lt05 710
2 290 11350 lt05 700
3 350 14000 lt05 710
3 Results and Discussion
It was established that calcium in the examined
compositions practically does not penetrate through the
mucous membrane into the solutions contained in the
receiving cells The insignificant amounts of calcium found in
the cells correspond to the concentration of calcium in isotonic
solution At the same time in all the cases the initial
concentration of calcium decreased essentially pointing to
penetration of HAP into the mucous membrane (Table 3)
Table 3 Residual concentration of calcium in the studied compositions
Composition Residual concentration of Ca
2 5197
3 4596
4 4053
As can be seen from table 3 in the absence of
transcutaneous conductors the colloidal solution of HAP
shows rather high penetrating activity in comparison with
crystal forms The greatest degree of diffusion of colloidal
HAP is provided by silicon glycerolates as evidenced by the
smallest residual concentration of calcium in the initial
solution A rather high absorbing ability of the mucous
membrane with respect to calcium is noted (Fig 2)
Fig 2 The amount of calcium passed into the mucous membrane 1 ndash HAP
(colloidal) 2 ndash HAP (suspension) + silicon glycerolates 3 ndash HAP (colloidal)
+ silicon glycerolates
The results obtained testify that the most active
transcutaneous conductors are silicon glycerolates In
composition 1 only ca 2 of the initial amount of silicon
diffuse through the membrane while ca 25 of silicon left in
the initial solution allow us to conclude that the main body of
calcium remains in the mucous membrane
In case of joint presence of silicon glycerolates and HAP
silicon like calcium does not pass through the membrane
which can also testify to the interaction between them
Since the interaction of HAP with organic substances takes
place by the surface adsorption type where the main
absorbent elements of HAP are calcium ions and phosphate
ions the ability of silicon glycerolates to promote HAP
diffusion is likely to be due to the appearance of CaminusOminusSi
PminusOminusSi and CaminusOminusC coordination bonds between them The
absence of chemical interaction giving rise to covalent bonds
has been proved experimentally The IR-spectra of the
compositions obtained during the interaction of colloid HAP
and silicon glycerolates taken in equimolar ratios at different
temperatures (20 and 60degC) did not reveal any visible changes
(displacement of characteristic frequencies and appearance of
new absorption bands) in comparison with the spectra of the
initial materials [11]
4 Conclusion
It was established that the biological activity of HAP
depends substantially on the size of particles (or grains) and is
more pronounced when the dispersion of a substance is higher
The research performed showed that colloidal HAP exhibits
higher penetrating ability in tissues than its crystal forms The
presence of silicon glycerolates promotes penetration of HAP
into the mucous membrane
Note that the presented results cannot be automatically
extrapolated to human organism as they are obtained in in
vitro experiments In a living organism the speed of
penetration of substances through a biological membrane
(skin mucous membrane) depends not only on its structure as
a barrier but also on its physiological state
The studies performed allow us to recommend HAP for
further research aimed at its practical application both as an
4 E A Bogdanova et al Transport Properties of Some Forms of Hydroxyapatite
independent medicine and as a component of pharmaceutical
compositions with improved regeneration of bone tissues and
enhanced therapeutic action
References
[1] Janick S Gabiga H Untersuchung der in vitro ndash freigabegeschwindigkeit von Isosorbiddinitrat aus einem transdermalen terapeutischen Membransystem Pharmazie 1989 44(1) 68
[2] Rajech D Gandi and Joseph R Robinson Bioadhesion in drug delivery Indian Pharm Sci 1988 50(3) 145-152
[3] Ziegenmeyer J TTS Transdermale Applikation von Arzneistoffen Pharm Ztg 1999 134(2) 24-30
[4] T G Khonina LP Larionov Rusinov GL et alrdquoSilicon glycerates possessing transcutaneous conductivity of drugs and glycerohydrogels based thereonrdquo RF Patent 2255939 published 10 July 2005 [in Russian]
[5] Sabirzyanov NA Khonina TG Evdokimova KV et al New materials for medicine Ekaterinburg UrO RAN 2006 pp 100-107 [in Russian]
[6] NА Sabirzyanov LP Larionov SP Yatsenko et alrdquoMethod for production of wound healing and osteoplastic agentrdquo RF Patent 2314107 published 10 January 2008 [in Russian]
[7] NА Sabirzyanov T G Khonina G I Ron SP Yatsenko et alrdquoAgent for treatment of inflammatory diseases of periodontiumrdquo RF Patent 2296556 published 10 April 2007 [in Russian]
[8] N G Sarkisyan G I Ron N A Sabirzyanov E A Bogdanova et alrdquoMethod for treatment of periodontitisrdquo RF Patent 2330645 published 10 August 2008 [in Russian]
[9] Sarkisyan N G Ron G I Khonina T G Bogdanova E A Sabirzyanov N A Experience of using drug formulations for treatment of periodontitis Uralskii meditsinskii zhurnal (Ural medical journal 2008 45(5) 104-106 [in Russian]
[10] SP Yatsenko NА Sabirzyanov lsquoMethod for production of hydroxyapatitersquo RF patent 2104924 published 20 February 1998 [in Russian]
[11] Е А Bogdanova lsquoThe physicochemical properties of bioactive composite materials based on calcium phosphates and organic silicon compoundsrsquo PhD thesis Federal State government-financed research institution Institute of Solid State Chemistry of the Ural Branch of the Russian Academy of Sciences Ekaterinburg Russia 2012 130 p [in Russian]
4 E A Bogdanova et al Transport Properties of Some Forms of Hydroxyapatite
independent medicine and as a component of pharmaceutical
compositions with improved regeneration of bone tissues and
enhanced therapeutic action
References
[1] Janick S Gabiga H Untersuchung der in vitro ndash freigabegeschwindigkeit von Isosorbiddinitrat aus einem transdermalen terapeutischen Membransystem Pharmazie 1989 44(1) 68
[2] Rajech D Gandi and Joseph R Robinson Bioadhesion in drug delivery Indian Pharm Sci 1988 50(3) 145-152
[3] Ziegenmeyer J TTS Transdermale Applikation von Arzneistoffen Pharm Ztg 1999 134(2) 24-30
[4] T G Khonina LP Larionov Rusinov GL et alrdquoSilicon glycerates possessing transcutaneous conductivity of drugs and glycerohydrogels based thereonrdquo RF Patent 2255939 published 10 July 2005 [in Russian]
[5] Sabirzyanov NA Khonina TG Evdokimova KV et al New materials for medicine Ekaterinburg UrO RAN 2006 pp 100-107 [in Russian]
[6] NА Sabirzyanov LP Larionov SP Yatsenko et alrdquoMethod for production of wound healing and osteoplastic agentrdquo RF Patent 2314107 published 10 January 2008 [in Russian]
[7] NА Sabirzyanov T G Khonina G I Ron SP Yatsenko et alrdquoAgent for treatment of inflammatory diseases of periodontiumrdquo RF Patent 2296556 published 10 April 2007 [in Russian]
[8] N G Sarkisyan G I Ron N A Sabirzyanov E A Bogdanova et alrdquoMethod for treatment of periodontitisrdquo RF Patent 2330645 published 10 August 2008 [in Russian]
[9] Sarkisyan N G Ron G I Khonina T G Bogdanova E A Sabirzyanov N A Experience of using drug formulations for treatment of periodontitis Uralskii meditsinskii zhurnal (Ural medical journal 2008 45(5) 104-106 [in Russian]
[10] SP Yatsenko NА Sabirzyanov lsquoMethod for production of hydroxyapatitersquo RF patent 2104924 published 20 February 1998 [in Russian]
[11] Е А Bogdanova lsquoThe physicochemical properties of bioactive composite materials based on calcium phosphates and organic silicon compoundsrsquo PhD thesis Federal State government-financed research institution Institute of Solid State Chemistry of the Ural Branch of the Russian Academy of Sciences Ekaterinburg Russia 2012 130 p [in Russian]
