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Percutaneous Absorption in baths

Percutaneous Absorption in baths. Effects of bathing. mechanical factors thermal factors chemical factors. Chemical Effects in Baths Target organs of primary reaction. direct to the skin Skin diseases indirect by skin stimulation to the general system Chronically inflammatory diseases

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Percutaneous Absorption in baths

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  1. Percutaneous Absorption in baths

  2. Effects of bathing • mechanical factors • thermal factors • chemical factors

  3. Chemical Effects in BathsTarget 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

  4. Chemical acute effectsby 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)

  5. Percutaneous 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.

  6. Percutaneous 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.

  7. Transfer of substances in bathing Solutions in water Output (elution) Input (deposition) Permeation (transfer) Chemical reaction Horny layer

  8. L/h mL/h 10 100 n-Pentanol CO2 Rn n-Butanol 1 Water 10 iso-Butanol H2S Ethanol 0,1 O2 He Ar H2 DMSO 1 N2 0,01 Permeability of skinAbsorption of gases and liquids through 2 m2 skin

  9. CO2 Radon H2S Permeability of skin of solutions in water 1000 µl solution/cm2/h 100 Octanol Methylsalicylat Heptanol Camphen 10 Phenylmercuryborate Estron Camphor Water 1 Propanol Progesterone Ethanol Methanol Water Testosterone DMSO Acetylsalicylic acid 0,1 Sodium Ferrum II Strontium Heparin Corticosteron Potassium Arsenic Sulphate Chloride Bromide Iodide Indomethacine Calcium Pertechnetate 0,01 Cortisone Salicylic acid Caesium Cobalt Cadmium Silver Hydrocortisone Ferrum III 0,001 Chromium III 0,0001 Selenite

  10. 1000 mg solution/cm2/h 100 10 1 Water 0,1 0,01 0,001 0,0001 Permeability of SkinSkin-Clearance of solutions Gases Volatile substances Amphophile substances Lipophile substances Hydrophile substances (ions)

  11. Percutaneous absorption of alcohols in watery solution (Scheuplein 1973) (l /cm2h) Distribution coefficienthorny cellsWater .6.91.12.55103050 Epidermis.5.5.81.22.561332526080 Dermis605335313024202526 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

  12. The limitation of percutaneous absorption is controlled by the horny layer

  13. Skin-Clearance is the measure of quantitative transfer for soluted substances through the skin Skin-Clearance = Diffusion coefficient x distribution coefficient function(membrane thickness)

  14. How can be calculated dose by skin-clearance? 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) 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)

  15. Low permeation rates could modify metabolic processes But percutaneous absorption only can be effective if natural depot concentration increase.

  16. Regional differences in water permeability of the skin** compared by thickness and number of cells of the horny layer (*Holbrook 1974,**Scheuplein 1971)

  17. Calculation of Skin-Clearance by use of blood levels for CO2

  18. Calculation of Skin-Clearance by use of renal elimination forCO2

  19. Blood level kinetic by percutaneous absorption

  20. Blood level and permanence of bathing Blood level Bath range In steady stateno steady state time

  21. Calculation example of Radon kinetic Skin Clearance = 200 µl/cm2 *h Concentration in water = 3 kBq/l Skin 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-1Blood 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

  22. Distribution of percutaneous absorbed radioactive Sulphur(Andrejev)

  23. Distribution of sulphur in the skin Sulphur is oxidized during percutaneous transfer. Reaction products are ineffective.

  24. Sulphur distribution in the horny layer

  25. Distribution of Salicylic acid in the horny layer Same distribution can be found for all indifferent substances in the horny layer

  26. Concentration gradient inside of the horny layer follows an exponential function The permeation rate decrease exponential by thickness of horny layer.

  27. Distribution model of penetrating substances in the horny layer

  28. Concentration of external applied substances 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.

  29. The natural endogenous substances in the horny layer

  30. Concentration of Sodium and Potassium in the horny layer of 10 patients

  31. Concentration range of Na, K, Si, Cl in the skin

  32. Range of trace elements in the skin

  33. Differentiation of skin cells 14 days are needed for total regeneration of the horny layer. 28 days are needed for total regeneration of the epidermis.

  34. Isotonia of horny layer is equivalent to 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 %

  35. Distribution of endogenous substances in the horny layer by example of the amino acids Concentration in all cell layers is nearly the same

  36. Endogenous substances of the horny 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.

  37. Transfer of water through the skin Percutaneous absorption and perspiration insensibilis 20 ml/h Lost of water without of stratum corneum disjunctum 250 ml/h without epidermis 800 ml/h Permeability of the intact horny layer in sito 2,5 ml/h

  38. Water 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.

  39. Elimination of water soluble substances of horny layer during bathing

  40. µmol/cm2 Amount in horny layer n = 10 0,2 Eliminationduring a bath Elimination by desquamation In one day 0,1 n = 10 0 Elimination of skin urea Elimination by one bath is regenerated in one week

  41. Lower than10 min mol%of Amino acids 25 10 - 30 min duration 20 More than 30 minr n = 14 15 10 n = 161 n = 17 5 0 Usage of bath duration and urea amount in the horny layer Persons with long bath durations have lower amount of natural moistening factors in the horny layer

  42. mol%of Amino acids No bath additives 18 16 Few Bath additives n = 93 14 12 Foam bathadditives 10 8 n = 63 6 n = 22 4 2 0 Usage of bath additives and urea amount in the horny layer Persons with usage of bath additives have lower amount of natural moistening factors n the horny layer

  43. Amino acid differences in horny layer by different persistence of bath (Unit: mol %)

  44. Amino acid-differences of the horny layer by use of foam bath additives (Unit : mol%)

  45. SER n=142+41 Intensive baths usage and allergic skin reactionsChange in amount of amino acids in horny layer ASN ASN GLU Persons with allergic skin GLU PRO PRO SER THR THR GLY GLY ASP ASP n=135+57 ALA UCS ALA UCS HAR HAR CIT CIT VAL VAL ARG ARG TYR ILE TYR ILE HIS HIS PHE LYS PHE LYS LEU LEU ORN Daily bathing persons ORN

  46. Inhibition of arginase-activity in horny layer by detergents Inhibition by use ofdodecyl sulphate Inhibitionby use ofsoaps Naturalinhibition 100% 50% 0%

  47. Therapeutic range in concentration of mineral waters Lower limit value Upper limit value Ineffective range Therapeutic range Toxic range • Therapeutic rangedependence on indication. • Dosis dependence on: • Application manner • bathing (concentration)drinking (amount of drinking)Inhaling (concentration) • Application frequencyApplication temperature

  48. Brine water saves the skinElution of Urocanic acid. Measurement of the bath water UV absorption 1 cm E 0,4 265 nm Water 0,3 0,2 27%NaCl 0,1 Minutes Bath persistence 0 5 35 45 25 15 55

  49. after 2nd bath in 6% brine after 1st bath in 6% brine before Concentration of Sodium and Potassium in horny layer after brine baths 7 6 5 4 Concentration in µg/cm2 3 Stratum corneum conjunctum 2 1 0 Skin surface Stripping with glue tape lowest layers

  50. after 2nd bath in 6% brine after 1st bath in 6% brine before Concentration of Sodium and Potassium in horny layer after brine baths 12 10 8 6 concentration in µg/cm2 Stratum corneum conjunctum 4 2 0 Skin surface Stripping with glue tape lowest layers

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