percutaneous absorption in baths. effects of bathing mechanical factors thermal factors chemical...
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Percutaneous Absorption in baths Percutaneous Absorption in baths
Effects of bathingEffects of bathing
mechanical factorsthermal factors chemical factors
Chemical Effects in BathsChemical Effects in BathsTarget organs of primary reactionTarget organs of primary reaction
Chemical Effects in BathsChemical Effects in BathsTarget organs of primary reactionTarget organs of primary reaction
direct to the skin Skin diseases
indirect by skin stimulation to the general system Chronically inflammatory diseases
by percutaneous absorption and elimination by the respiratory system Respiratory diseases
by percutaneous absorption and effect in the general system Diseases of circulatory system and central nervous system
Chemical acute effectsChemical acute effectsby substances in bath watersby substances in bath waters
Skin irritation followed by stimulation of the anti-inflammatory endogenous power of the body (Sulphur, Radon)
Skin irritation followed by decrease of pathologic activated pain sensitivity (Sulphur, Radon)
Improvement of reologic blood factors (CO2)
sedative (Oil of Cymbopogon winterianus or Valerianae officinalis radix)
Antiphlogistic in the skin (Camomile, Matricariae flos) Exsiccation of the skin (Tannic acid) Bronchospasmolytic by elimination (Oil of conifers)
Percutaneous absorptionPercutaneous absorption
Penetration into the skin– Substance disappear on the skin surface. One part disappear by
permeation through the skin an other part is absorbed in the skin.
Permeation through the skin– Substance cross the skin. Permeation amount could be measured
below the skin.
Absorption in the tissue– Substance is storage in a part of tissue. Absorbed amount could be
measured in the tissue.
Percutaneous absorptionPercutaneous absorption
Absorption through the skin– Substance is absorbed by permeation into the circularly
system and will be transported in different compartments. Absorption amount is only one part of permeation amount. Absorption amount can be calculated by the blood level and the renal elimination if the kinetic of distribution in the body is known.
Transfer of substances in Transfer of substances in bathingbathing
Output (elution)Output (elution) Input (deposition)Input (deposition) Permeation (transfer)Permeation (transfer) Chemical reactionChemical reaction
Horny layerHorny layer
Solutions in waterSolutions in water
Permeability of skinPermeability of skinAbsorption of gases and liquids through 2 mAbsorption of gases and liquids through 2 m22 skin skin
L/h10
1
0,1
0,01N2
He Ar H2
H2SO2
CO2Rn
mL/h
100
10
1
n-Pentanoln-Butanol
Wateriso-Butanol
Ethanol
DMSO
0,0001
0,001
0,01
0,1
1
10
100
1000µl solution/cm2/h
Cortisone
Corticosteron
Indomethacine
Salicylic acid
Hydrocortisone
Heparin
Acetylsalicylic acidDMSO
Progesterone
Testosterone
Estron
Methylsalicylat
IodideSulphate
Strontium
CobaltSilver
Pertechnetate
ArsenicBromide
Ferrum II
Selenite
Chromium IIIFerrum III
CadmiumCaesiumCalciumChloridePotassium
Sodium
Phenylmercuryborate
MethanolWater
H2S
RadonCO2
Permeability of skin Permeability of skin of solutions in waterof solutions in waterPermeability of skin Permeability of skin of solutions in waterof solutions in water
Water EthanolPropanolCamphor
CamphenHeptanolOctanol
Permeability of SkinPermeability of SkinSkin-Clearance of solutionsSkin-Clearance of solutions
Gases
Volatile substances
Amphophile substances
Lipophile substances
Hydrophile substances (ions)
Water
mg solution/cm2/h 1000
100
10
1
0,1
0,01
0,001
0,0001
Percutaneous absorption of alcohols Percutaneous absorption of alcohols in watery solutionin watery solution
(Scheuplein 1973) (Scheuplein 1973)
(l /cm2h)
Epidermis.5.5.8
1.22.561332526080
Epidermis.5.5.8
1.22.561332526080
Dermis605335313024202526
Dermis605335313024202526
Distribution coefficient horny cells
Water
.6
.91.12.55
103050
Distribution coefficient horny cells
Water
.6
.91.12.55
103050
Water Methanol Ethanol Propanol Butanol Pentanol Hexanol Heptanol Octanol Nonanol Decanol
Water Methanol Ethanol Propanol Butanol Pentanol Hexanol Heptanol Octanol Nonanol Decanol
Permeation of alcohols increase proportional by the distribution coefficient between horny cell matrix and water
Permeation of alcohols increase proportional by the distribution coefficient between horny cell matrix and water
The limitation of percutaneous The limitation of percutaneous absorption is controlled by the absorption is controlled by the
horny layerhorny layer
Skin-Clearance is the measure of Skin-Clearance is the measure of quantitative transfer for soluted quantitative transfer for soluted
substances through the skinsubstances through the skin
Skin-Clearance = Diffusion coefficient x distribution coefficient function(membrane thickness)
Skin-Clearance = Diffusion coefficient x distribution coefficient function(membrane thickness)
How can be calculated dose by How can be calculated dose by skin-clearance?skin-clearance?
Dose =
Skin-Clearance x Skin area x Concentration of soluted substance x bathing time
Dose =
Skin-Clearance x Skin area x Concentration of soluted substance x bathing time
Dose is limited by the substance amount on the skin
(Never a limit is taken into account in bath tubs)
Dose is limited by the substance amount on the skin
(Never a limit is taken into account in bath tubs)
Skin-Clearance be valid by optimal condition of penetration(Bath, moist skin, occlusion)
Skin-Clearance be valid by optimal condition of penetration(Bath, moist skin, occlusion)
Influence of temperature is very low (low variability of skin temperature) (Q10 : 1,1-1,4)
Influence of temperature is very low (low variability of skin temperature) (Q10 : 1,1-1,4)
Low permeation rates could modify Low permeation rates could modify metabolic processesmetabolic processes
Activation Inhibition K, NH4 Li, Na, K, Cs Ca, Mg, Mn Ca, Mg Zn, Cd Zn, Cd Fe, Co, Ni Cu, Ag, Au, Hg, Pb F, Cl, J F, Cl, Br PO4 PO4, P2O7, AsO4, AsO3 H2S, GSH H2S, SH O3 SO4, SO3, BO4, NO2 UV CN, CO, J2
But percutaneous absorption only can be effective if natural depot concentration increase.
But percutaneous absorption only can be effective if natural depot concentration increase.
Regional differences in water permeability of Regional differences in water permeability of the skin** compared by thickness and number the skin** compared by thickness and number
of cells of the horny layerof cells of the horny layer ( (*Holbrook 1974,**Scheuplein 1971)*Holbrook 1974,**Scheuplein 1971)
Skin region Water mg / cm2 / h
Thickness m
Number of cells
Abdomen 0.34 6.9 – 9.8* 15 – 20.9* Arm volar 0.31 8.1 – 16.2* 16.7 – 30* Back 0.29 8.2 – 11.3* 14 – 21.1* Forehead 0.85 13.0 Scrotum 1.70 5.0 Back of the hand 0.56 49.0 Palm 1.14 400 Sole of the foot 3.90 600
Calculation of Skin-Clearance by Calculation of Skin-Clearance by use of blood levels for COuse of blood levels for CO22
Calculation of Skin-Clearance by Calculation of Skin-Clearance by use of renal elimination foruse of renal elimination for COCO22
Blood level kinetic by Blood level kinetic by percutaneous absorptionpercutaneous absorption
Blood level and permanence of bathingBlood level and permanence of bathing
Bath range
In steady state
no steady state
Blood levelBlood level
timetime
Calculation example of Radon kineticCalculation example of Radon kinetic
Skin Clearance = 200 µl/cm2 *hConcentration in water = 3 kBq/lSkin area = 2 m2
Absorption rate = 200 x 3 x 2/100 = 12 kBq/h
Skin Clearance = 200 µl/cm2 *hConcentration in water = 3 kBq/lSkin area = 2 m2
Absorption rate = 200 x 3 x 2/100 = 12 kBq/h
Distribution volume = 20 l of 80 kg BWElimination constant = 20 h-1
Blood level in steady state= 12 kBq/h / (20 l x 20 h-1) = 0,030 kBq/lBlood level by 10 min. bath duration = 0,030 x (1-e-20 h-1 x 10 min) = 0,029 kBq/l
Water concentration : Blood level = 100 : 1
Distribution volume = 20 l of 80 kg BWElimination constant = 20 h-1
Blood level in steady state= 12 kBq/h / (20 l x 20 h-1) = 0,030 kBq/lBlood level by 10 min. bath duration = 0,030 x (1-e-20 h-1 x 10 min) = 0,029 kBq/l
Water concentration : Blood level = 100 : 1
Distribution of percutaneous Distribution of percutaneous absorbed radioactive Sulphurabsorbed radioactive Sulphur (Andrejev)(Andrejev)
Distribution of sulphur in the skinDistribution of sulphur in the skin
Sulphur is oxidized during percutaneous transfer. Reaction products are ineffective.
Sulphur is oxidized during percutaneous transfer. Reaction products are ineffective.
Sulphur distribution in the horny layerSulphur distribution in the horny layer
Distribution of Salicylic acid in Distribution of Salicylic acid in the horny layerthe horny layer
Same distribution can be found for all indifferent substances in the horny layer
Same distribution can be found for all indifferent substances in the horny layer
Concentration gradient inside of the horny Concentration gradient inside of the horny layer follows an exponential functionlayer follows an exponential function
The permeation rate decrease exponential by thickness of horny layer.
The permeation rate decrease exponential by thickness of horny layer.
Distribution model of penetrating Distribution model of penetrating substances in the horny layersubstances in the horny layer
Concentration of external applied Concentration of external applied substances in the horny layersubstances in the horny layer
Concentration in the horny layer decrease by penetration deepness.
Around the lowest or last layer the concentration is about 1/100 of the surface concentration.
The natural The natural endogenous endogenous
substances in substances in the horny the horny
layerlayer
Concentration of Sodium and Potassium in Concentration of Sodium and Potassium in the horny layer of 10 patientsthe horny layer of 10 patients
Concentration range of Concentration range of Na, K, Si, Cl in the skinNa, K, Si, Cl in the skin
Range of trace elements in the skinRange of trace elements in the skin
Differentiation of skin cellsDifferentiation of skin cells
14 days are needed for total regeneration of the horny layer.
28 days are needed for total regeneration of the epidermis.
14 days are needed for total regeneration of the horny layer.
28 days are needed for total regeneration of the epidermis.
Isotonia of horny layer is equivalent to Isotonia of horny layer is equivalent to about 6 % NaCl !about 6 % NaCl !
By differentiation all inorganic substances in cells are transferred into the horny layer.But the amount of water in the horny layer is about 10% and in stratum spinosum about 65%.The concentration of inorganic substances in water increase by factor 6.5. Result in isotonia of the horny layer in comparison to the living tissue of the body is 0,9 x 6,5 = 6 %
By differentiation all inorganic substances in cells are transferred into the horny layer.But the amount of water in the horny layer is about 10% and in stratum spinosum about 65%.The concentration of inorganic substances in water increase by factor 6.5. Result in isotonia of the horny layer in comparison to the living tissue of the body is 0,9 x 6,5 = 6 %
Distribution of endogenous substances in the Distribution of endogenous substances in the horny layer by example of the amino acidshorny layer by example of the amino acids
Concentration in all cell layers is nearly the sameConcentration in all cell layers is nearly the same
Endogenous substances of the Endogenous substances of the horny layerhorny layer
Concentration in all cell layers is nearly the same. Inorganic substances in the horny layer are transferred
by differentiation of epidermal cells. The part of sweat is unimportant low.
Concentration of inorganic substances in the horny layer is about 6.5 times more than in living deeper cells.
External effects (sweating, washing) decrease normally only the concentration of the outer third of the horny layer.
Transfer of water through the skinTransfer of water through the skinPercutaneous absorption and perspiration insensibilis 20 ml/h
Lost of water without of stratum corneum disjunctum 250 ml/hwithout epidermis 800 ml/h
Permeability of the intact horny layer in sito 2,5 ml/h
Percutaneous absorption and perspiration insensibilis 20 ml/h
Lost of water without of stratum corneum disjunctum 250 ml/hwithout epidermis 800 ml/h
Permeability of the intact horny layer in sito 2,5 ml/h
Water uptake into the horny layerWater uptake into the horny layer
During bathing about 1 µl water per cm2 body surface is deposited in horny layer in few minutes.In the horny layer a solution of 24-43% resulted by endogenous water soluble substances with 0,24 – 0,43 mg/cm2.In relation to higher concentration of salt in bath water the uptake of water into the skin decrease.In saturated salt solutions no water uptake can be found.By water uptake and swelling the permeability of horny layer increase.
During bathing about 1 µl water per cm2 body surface is deposited in horny layer in few minutes.In the horny layer a solution of 24-43% resulted by endogenous water soluble substances with 0,24 – 0,43 mg/cm2.In relation to higher concentration of salt in bath water the uptake of water into the skin decrease.In saturated salt solutions no water uptake can be found.By water uptake and swelling the permeability of horny layer increase.
Elimination of water soluble substances Elimination of water soluble substances of horny layer during bathingof horny layer during bathing
Elimination of skin ureaElimination of skin ureaElimination of skin ureaElimination of skin urea
0
0,1
0,2
n = 10
n = 10
Amount inhorny layer
Eliminationduring a bath Elimination by
desquamationIn one day
µmol/cm2
Elimination by one bath is regenerated in one weekElimination by one bath is regenerated in one week
Usage of bath duration and urea Usage of bath duration and urea amount in the horny layeramount in the horny layer
Usage of bath duration and urea Usage of bath duration and urea amount in the horny layeramount in the horny layer
0
5
10
15
20
25
n = 14
n = 161
n = 17
Lower than 10 min
10 - 30 minduration
More than 30 minr
mol%of Amino acids
Persons with long bath durations have lower amount of natural moistening factors in the horny layer
Persons with long bath durations have lower amount of natural moistening factors in the horny layer
Usage of bath additives and urea Usage of bath additives and urea amount in the horny layeramount in the horny layer
Usage of bath additives and urea Usage of bath additives and urea amount in the horny layeramount in the horny layer
0
2
4
6
8
10
12
14
16
18No bath additives
Few Bath additives
Foam bathadditives
n = 93
n = 63
n = 22
mol%of Amino acids
Persons with usage of bath additives have lower amount of natural moistening factors n the horny layerPersons with usage of bath additives have lower amount of natural moistening factors n the horny layer
Amino acid differences in horny Amino acid differences in horny layer by different persistence of bath layer by different persistence of bath
(Unit: mol %)(Unit: mol %)Substanz n = 14
10 minn = 161
10 –30 minn = 17
30 minHarnstoff 21.04 13.40 8.35Asparagin 1.55 0.83 0.48Prolin 1.54 2.69 0.96Citrullin 7.19 9.14 7.78Histidin 6.50 5.03 4.95Arginin 3.80 2.52 2.22
Amino acid-differences of the horny layer by Amino acid-differences of the horny layer by use of foam bath additives (Unit : mol%)use of foam bath additives (Unit : mol%)
n = 22 foam additive high quality
Substanz n = 93 no additives
n = 63 simple foam additives
6.99 Harnstoff 16.59 10.05 3.08 Asparaginsre. 3.98 3.25 33.15 Serin 29.27 30.17 0.50 Asparagin 1.03 0.59 1.80 Glutaminsre. 2.61 2.17 2.55 Prolin 1.78 2.28 8.35 Citrullin 8.28 10.05 1.30 Isoleucin 1.56 1.41 1.09 Leucin 1.30 1.19 1.39 Tyrosin 1.68 1.72 2.71 Ornithin 3.16 2.01 1.27 Lysin 1.79 1.40 4.91 Histidin 5.57 4.48 1.96 Arginin 2.90 2.34
Intensive baths usage and allergic skin Intensive baths usage and allergic skin reactionsreactions
Change in amount of amino acids in horny layerChange in amount of amino acids in horny layer
Intensive baths usage and allergic skin Intensive baths usage and allergic skin reactionsreactions
Change in amount of amino acids in horny layerChange in amount of amino acids in horny layer
SERSER
ORNORN
LYSLYSHISHIS
ARGARG
HARHAR
UCSUCS
ASPASP
THRTHR
VALVAL
ILEILE
LEULEU
TYRTYR
PHEPHE
ASNASN
GLUGLU
PROPRO
GLYGLY
ALAALA
CITCIT
Daily bathingDaily bathing persons persons
Persons withPersons withallergic skinallergic skin
SERSER
ASNASN
GLUGLUPROPRO
GLYGLY
ALAALA
CITCIT
VALVAL
ILEILE
LEULEU
TYRTYR
PHEPHE
ORNORN
LYSLYS
HISHIS
ARGARG
HARHAR
UCSUCS
ASPASP
THRTHR
n=142+41 n=135+57
Inhibition of arginase-activity in horny Inhibition of arginase-activity in horny layer by detergentslayer by detergents
Inhibition of arginase-activity in horny Inhibition of arginase-activity in horny layer by detergentslayer by detergents
0%
50%
100%Naturalinhibition
Inhibitionby use ofsoaps
Inhibition by use ofdodecyl sulphate
Therapeutic range in concentration of Therapeutic range in concentration of mineral watersmineral waters
Therapeutic range in concentration of Therapeutic range in concentration of mineral watersmineral waters
Ineffective range Therapeutic range Toxic range
• Therapeutic range dependence on indication.• Dosis dependence on:
Application mannerbathing (concentration)drinking (amount of drinking)Inhaling (concentration)
Application frequencyApplication temperature
Lower limit value Upper limit value
Brine water saves the skinBrine water saves the skinElution of Urocanic acid. Measurement of the bath water UV absorptionElution of Urocanic acid. Measurement of the bath water UV absorption
Brine water saves the skinBrine water saves the skinElution of Urocanic acid. Measurement of the bath water UV absorptionElution of Urocanic acid. Measurement of the bath water UV absorption
Water
27%NaCl
0,4
0,3
0,2
0,1
5 15 25 35 45 55
Minutes Bath persistence
E1 cm265 nm
0
Concentration of Sodium and Potassium Concentration of Sodium and Potassium in horny layer after brine bathsin horny layer after brine baths
Concentration of Sodium and Potassium Concentration of Sodium and Potassium in horny layer after brine bathsin horny layer after brine baths
beforebefore
after 1st bath in 6% brineafter 1st bath in 6% brine
after 2nd bath in 6% brineafter 2nd bath in 6% brine
Co
nce
ntr
atio
n in
µg
/cm
2
Stripping with glue tapeSkin surface lowest layers
Stratum corneum conjunctum
7
0
1
6
2
3
4
5
after 1st bath in 6% brineafter 1st bath in 6% brine
after 2nd bath in 6% brineafter 2nd bath in 6% brine
con
cen
trat
ion
in µ
g/c
m2
Stripping with glue tapeSkin surface lowest layers
Stratum corneum conjunctum
12
0
10
2
4
6
8
Concentration of Sodium and Potassium Concentration of Sodium and Potassium in horny layer after brine bathsin horny layer after brine baths
beforebefore
Calculation of concentration balance of Calculation of concentration balance of uptake and elimination of sodiumuptake and elimination of sodium
Concentration is balanced by concentration of minerals in Sea waterConcentration is balanced by concentration of minerals in Sea water
Are brine baths effective?Are brine baths effective?
Effects of salt solutions which are components of the skin too can be effective by osmotic irritation of the skin.Higher uptake than elimination of NaCl is possible by concentrations higher than NaCl in sea water. Osmotic irritation is possible in concentrations higher than 6%.In damaged horny layer (dry or fissured skin) osmotic irritation is possible by lower concentration.Inter individual variation is very high in effectiveness.
Effects of salt solutions which are components of the skin too can be effective by osmotic irritation of the skin.Higher uptake than elimination of NaCl is possible by concentrations higher than NaCl in sea water. Osmotic irritation is possible in concentrations higher than 6%.In damaged horny layer (dry or fissured skin) osmotic irritation is possible by lower concentration.Inter individual variation is very high in effectiveness.
End of End of SlidesSlides