TRANSDERMAL VAPOR COLLECTION METHOD AND APPARATUS

Abstract: A method for the non-invasive, continuous collection of substances which transdermally migrate to and vaporize at the surface of the skin of a subject comprises providing a binding reservoir material (12) juxtaposed at the surface of the skin of a subject, and continuously maintaining the binding reservoir material in a substantially airtight relation with the skin surface over an entire collection period. The apparatus comprises a binding reservoir material (12) and means (14) for continuously maintaining the binding reservoir material juxtaposed at the skin surface of the subject in a substantially airtight relation with the skin surface.

Description: TRANSDERMAL VAPOR COLLECTION METHOD AND APPARATUS RELATED APPLICATION This application is a continuation-in-part of U.S. patent application serial No. 660,778 filed February 11, 1985. FIELD OF THE INVENTION The present invention relates to a method and apparatus for the non-invasive, continuous collection of substances which transdermally migrate to and vaporize at the surface of the skin of a subject. More particularly, the present invention relates to a transdermal vapor • collection method and apparatus which employ a binding reservoir material for collecting the vapors and preventing their escape into the environment or their migration back into the skin. BACKGROUND OF THE INVENTION Many chemicals enter the bodies of animals, both human and nonnuman, in various manners, for example, across skin, by inhalation, by oral ingestion and by 630 d i rect inj ection through the skin into subcutaneou tissues and muscle or directly into blood vessels. Thes chemi cal s a re d is tr i buted in the body via bloo circulation. Owing to concentration gradients, a smal portion of the circulating chemicals, or one or more o thei r metaboli tes , may migrate outwardly from ski capillaries, across the epidermis and stratum corneum t the skin surface . If the thus migrated chemicals o metabolites are vaporous at the skin surface temperature they will escape from the skin surface into the adjacen environment. Additionally , gases such as oxygen an carbon dioxide in capillary blood also diffuse to the ski surface and escape. Various methods and apparatuses are known in th a r t fo r assessing human exposure to chem cals b monitoring and/or collecting substances which migrate to subj ect ' s skin surface . For example , Applicant ' copending application serial No . 660 , 778 discloses dermal substance collection device for the transderma collection of non- volatile chemicals. However, the devic disclosed therein includes a fluid conduit between t skin surface and the binding component, a feature which i counterproductive for the collection of chemicals in t vapor state. Similarly, the Phillips U. S . patent N 4,595,011 discloses a transdermal dosimeter for monitori exposure to chemical agents which includes a fluid pha serving as a dermal contact bridge. Peck et al in "A Non-Invasive Transepider Toxicological Monitoring Device" , Pittsburgh Conferen and Exposition on Analytical Chemistry and Appli Spectroscopy" , March 9 , 1982, Meeting Abstracts Book, pa 366 , d isclose a transepidermal device including adhesive plastic chamber containing sodium chlorid impregnated absorbent pads and an activated charco impregnated disk for capturing a xenobiotic to prevent back transfer from the collection device into the body. Similarly, the Phillips U.S. patent No. 4,329,999 discloses a patch including sodium chloride-impregnated absorbent pads for absorbing sweat from the skin surface of a patient. Sodium chloride interferes with the collection of chemicals which are in the vapor state. The Delpy et al U.S. patent No. 4,396,017 discloses a transcutaneous gas sensor including a sensing electrode which is applied to the body surface of a patient with an electrolyte layer between the electrode and the patient's body. Gas which has diffused through the patient's body from his blood to the body surface results in an electrochemical reaction at the exposed surface of the electrode. Similarly, the Dali et al U.S. patent No. 4,280,505 discloses a transcutaneous gas sensor probe for the measurement of trancutaneous gases emitted through the skin of a living body. Additional methods are also known for determining the presence of various chemicals in the body. For example, tissue biopsies and blood sampling are used but are disadvantageous owing to their invasive character. Other methods such as collection of urine or saliva are disadvantageous owing to the difficulty of obtaining continuous monitoring. A need exists for a method and apparatus for the non-invasive and continuous collection of substances which transdermally migrate to and vaporize at the surface of the skin of a subject. SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a method for the non-invasive and continuous collection of substances which transdermally migrate to and vaporize at the surface of the skin of a subject. It is a related object to provide an apparatu for the non-invasive and continuous collection O substances which transdermally migrate to and vaporize a the surface of the skin of a subject. It is a furthe object of the invention to provide a method whic facilitates the subsequent analysis of collected vapor and assessment of body conditions and exposures. These and additional objects are provided by th method and apparatus of the present invention. Mor specifically, the present invention relates to a metho for the non-invasive, continuous collection of substance which transdermally migrate to and vaporize at the surfac of the skin of a subject. The method comprises providin a binding reservoir material" juxtaposed at the surface o the skin of the subject, and continuously maintaining th binding reservoir in a substantially airtight relatio with the skin surface over an entire collection period The substances which migrate to and vaporize at the ski surface are collected in the binding reservoir and ar prevented from escaping into the environment or migratin back into the skin. The present invention further relate ' to an apparatus for the non-invasive, continuou collection of substances which transdermally migrate t and vaporize at the surface of the skin of a subject. Th apparatus comprises a binding reservoir material, a means for continuously maintaining the binding reservo material juxtaposed at the surface of the skin of subject in a substantially airtight relation with the ski surface over an entire collection period. Thus, wh substances migrate to and vaporize at the skin surfac they are collected in the binding reservoir and a prevented from escaping into the environment or fr migrating back into the skin. Additional objects and advantages of the method and apparatus of the present invention will become more apparent in view of the following detailed description. DESCRIPTION OF THE DRAWINGS The following detailed description will be more fully understood in view of the drawing in which: Fig. 1 sets forth an enlarged cross-sectional view of an embodiment of the apparatus according to the present invention; and Fig. 2 sets forth an exploded perspective view of the apparatus according to the present invention as set forth in Fig. 1. DETAILED DESCRIPTION The present invention comprises a method and apparatus for the non-invasive and continuous collection of substances which transdermally migrate to and vaporize at the surface of the skin of a subject. The method and apparatus are useful for collecting vapors from the skin surface of both human and nonhuman animals. The method and apparatus are useful for various applications including, for example, the monitoring of exposure to hazardous chemicals such as industrial solvents, pesticides, and various other chemical agents, monitoring exposure to volatile drugs of abuse such as ethanol, and monitoring exposure to environmental volatile toxic chemicals. The method of the present invention comprises providing a binding reservoir material juxtaposed at the surface of the skin of a subject, which binding reservoir material is capable of collecting and retaining substances in the vapor phase. Charcoal material is a highly advantageous binding reservoir material for collecting 30 ' substances in the vapor phase. Additionally, when th charcoal is in a dry condition, the vapor collection i unimpeded by the presence of a fluid barrier mediu interposed between the skin surface and the collectio device . A preferred charcoal material is activate charcoal or activated carbon which is obtained by th destructive distillation of various carbonaceous material followed by an " activation" process which usuall comprises heating the resultant material at a hig temperature, for example, 800 to 900°C, in the presence o steam or carbon dioxide to provide a porous interna structure. Alternatively, the binding reservoir materia may comprise other materials which a re capable o collecting and retaining substances in the vapor phase For example, the binding reservoir material may compris molecula r s ieve materials , namely alkaline meta aluminosilicates similar to natural clays and feldspars which comprise networks of empty pores and cavities gene rally of uni form s i ze . Molecular sieves a r pa rticularly suitable for collecting alcohols whic migrate to and vaporize at the skin surface. Silica gel a re also sui table for use as the binding reservoi material as are silica gels which have been modified wit aromatic or aliphatic group-containing silanes. Activate a lum i na s , i on excha nge res i ns , f o r ex amp le cholestyramine, and chelating agents are also suitable fo use as the binding reservoir material . The bindin reservoir material should not include a liquid componen since liquids generally inhibit the collection of vapo substances. Thus, the binding reservoir material shoul be in solid or semi-solid form. In a preferred embodiment, the binding reservo material is impregnated on a carrier member. The carri member may be formed of any number of substantially iner materials, for example, cloth or a perforated or porous plastic material. It is preferred that the carrier member is flexible in order to conform to the skin surface. A preferred carrier material comprises the polytetrafluoroethylene materials sold under the trade name Tefloπ=*. The method according to the present inventio further comprises the step of continuously maintaining the binding reservoir material in a substantially airtight relation with the skin surface over the collection period. The airtight relation of the binding reservoir material with the skin surface serves two purposes. First, the airtight relation insures collection of substances emanating only from the skin surface and prevents contamination of the binding reservoir material by environmental vapors. Second, the airtight relation establishes total skin-surface occlusion which results in hydration of the stratum corneum. Hydration of the stratum corneum enhances the transdermal migration of various substances since many chemicals permeate the hydrated stratum corneum faster than they permeate the dry stratum corneum. In a preferred embodiment of the present invention, the binding reservoir material is maintained in a substantially airtight juxtaposed relation with the skin surface by means of an airtight, flexible, adhesive cover means. The cover may be formed, for example, from a metal foil or from an impermeable plastic film material. It is preferred that at least a portion of the cover means includes an adhesive coating for adhering the cover means to the skin surface in an airtight manner. Fig. 1 discloses an enlarged cross-sectional view of an embodiment of the apparatus 10 according to the 30 8 present invention. The apparatus includes a bindin reservoir material 12 and cover means 14 for maintainin the binding reservoir material juxtaposed at the surfac of the skin of a subject in a substantially airtigh relation with the skin surface. As set forth in Fig. 1, surfaces 16 of the cover means are provided with a adhesive coating for adhering the cover means to the ski surface of the subject. The transdermal collectio apparatus may further include a removable impermeabl cover means 18 which covers the portion of the bindin reservoir material adapted for juxtaposition at the ski surface prior to use of the apparatus. The cover prevent contamination of the binding reservoir material prior t use of the apparatus and is adapted to be removed from th apparatus prior to use. Materials suitable for use as th removable cover include metal foils and impermeabl plastic films. Fig. 2 sets forth an exploded perspectiv view of the transdermal vapor collection apparatus of th present invention. By juxtaposition of the binding reservoir at th skin surface with an occlusive, airtight cover means, bod chemicals which have transdermally migrated to an vaporized at the skin surface are collected. The amoun of collected chemicals is proportional to the time integrated blood concentration of the subject chemical The binding reservoir material binds the vaporou substances and prevents them from escaping into th environment or from migrating back into the skin. In a preferred embodiment of the method of t present invention, the skin surface on which the bindin reservoir material is to be positioned is first cleane prior to providing the binding reservoir materia juxtaposed thereto. For example, the skin surface may cleansed and defatted by gently scrubbing with isoprop alcohol or the like. The binding reservoir material may be juxtaposed at the skin surface of the subject in a substantially airtight relation with the skin surface for a period of time which is dependent on the target vapor substance which is to be collected. For example, the binding reservoir may be maintained at the skin surface for a time period ranging from several minutes to several days. Once the collection period is complete, the binding reservoir material may be removed from the skin surface for further analysis. For example, when the binding reservoir material comprises a charcoal impregnated carrier, it may be immersed in a predetermined amount of an organic solvent in order to transfer the collected vapors from the binding reservoir material to the organic solvent. One suitable organic solvent comprises 1 hexane. The solvent may then be subjected to analysis, for example, by gas chromatography, in order to determine the amount and character of the collected substance. The method and apparatus of the invention are illustrated by the following example. ' EXAMPLE This example of the method and apparatus for transdermal vapor collection according to the present invention involves the collection of isoflurane through the skin of a living " fuzzy" rat. Transdermal vapor collection devices including an activated charcoal binding reservoir material are placed on the back or the abdomen of the ra t prior to intraveneous administration of isoflurane. The intraveneous infusion of isoflurane is in the form of one or more bolus injections or may be maintained as a constant infusion for a prescribed time per iod . Generally , the transdermal vapor collection dev ices may be removed a t va rious times during and 4630 10 following the end of the infusion period. Once removed the binding reservoir component of the device is placed i a small volume of pesticide grade hexane for extraction o the isoflurane and subsequent quantitative analysis by ga chromatography. Blood samples drawn during and after th infusions are also analyzed by gas chromatography t determine the whole blood isoflurane concentration resulting from isoflurane infusions. The amount o isoflurane in the transdermal vapor collection device ma be related to the concentration of isoflurane in the bloo by the following relationship: TCD(amt) - Kp x AUC x A where, TCD(amt) is the amount of isoflurane in th transdermal vapor collection device in micrograms, Kp i an "apparent" permeability coefficient in cm/min, AUC i the area under the isoflurane blood concentration-tim curve in mcg-min/ml, and A is the surface area of th transdermal vapor collection device in cm . In a representative experiment, the infusio • pump was set to deliver 12.5 mcl/min of a solutio containing 120 mg/ml of isoflurane for 98.5 minutes (tota dose of infused isoflurane was 147.4 mg) into a "fuzzy rat weighing 364 grams. The average amount of isoflura collected in four transdermal vapor collection devic removed from the rat's back at the end of the infusi period, extracted in hexane and assayed by ga chromatography, was 0.8 meg (+/- 0.2 meg, standar deviation). Since the area under the isoflurane blo concentration- time curve from the beginning of infusion the time of TCD removal was 2364 mcg-min/ml, and t surface area of the TCD was 0.95 cm , the calculat permeability coefficient according to the abo 11 relationship was 3.5 x 10 — 4 +/- 8.0 x 10 —5 cm/min (mean +/- standard deviation, n-4). Thus, the method and apparatus of the present invention provide non-invasive and continuous collection of substances which transdermally migrate to and vaporize at the skin surface of a subject in a simple manner. Moreover, the method and apparatus of the present invention are readily adaptable to subsequent methods for measuring and characterizing collected substances. The preceding examples of materials suitable for use in connection with the method and apparatus of the present invention are set forth to illustrate specific embodiments of the invention and are not intended to limit the scope of the methods and apparatus of the present invention. Additional embodiments and advantages within the *scoρe of the claimed invention will be apparent to one of ordinary skill in the art.

Claims: WHAT IS CLAIMED IS: 1.- A method for the non-invasive continuous collection of substances which transdermally migrate to and vaporize at the surface of the skin of a subject / comprising (a) providing a binding reservoir material juxtaposed at the surface of the skin of the subject, and (b) continuously maintaining the binding reservoir material in a substantially- airtight relation with the skin surface over an entire collection period, ' whereby substances which have migrated to and vaporized at the skin surface are collected in the binding reservoir material and are prevented from escaping into the environment or migrating back into the skin. * 2. A method as defined by claim 1, wherein the binding reservoir material is in a solid or semi-solid form. 3. A method as defined by claim 1 / wherein the binding reservoir material is selected from the group consisting of charcoal, molecular sieve materials, silica gels, silica gels modified with aromatic or aliphatic group-containing silanes, ion exchange resins and chelating agents. 4. A method as defined by claim 1, wherein the binding reservoir material is impregnated on an inert carrier member. 5. A method as defined by claim 4, wherein the carrier is formed of a polytetrafluoroethylene material. 6. A method as defined by claim 1, wherein the binding reservoir material is maintained in a substantially airtight relation with the skin surface by an airtight, flexible, adhesive cover means. 7. A method as defined by claim 6, wherein the cover means is formed from a material selected from metal foils and impermeable plastic films, and at least a portion of the cover means includes an adhesive coating. 8. A method as defined by claim 1, wherein the skin surface is cleaned prior to providing the binding reservoir material juxtaposed thereto. 9. A method as defined by claim 1, wherein once the collection period is complete, the binding reservoir material is removed from the skin surface and is immersed in a predetermined quantity of organic solvent, whereby the collected vapors are transferred from the binding reservoir material to the organic solvent. 630 14 10. An apparatus for the non-invasive, continuous collection of substances which transdermally migrate to and vaporize at the surface of the skin of a subject, comprising (a) a binding reservoir material, and (b) means for continuously maintaining the binding reservoir material juxtaposed at the surface of the skin of the subject in a substantially airtight relation wit the skin surface over an entire collection period, whereby when substances migrate to and vaporize at the ski surface they are collected in the binding reservoi material and are prevented from escaping into th environment or migrating back into the skin. 11. An apparatus as defined by cl*aim 10 wherein the binding reservoir material is in a solid o semi-solid form. 12. An apparatus as defined in claim 10 wherein the binding reservoir material is selected fro the group consisting of charcoal, molecular siev •materials, silica gels, silica gels modified with aromati or aliphatic group-containing silanes, ion exchange resin and chelating agents. 13. An apparatus as defined by claim 10 wherein the binding reservoir material is impregnated o an inert carrier member. 14. An apparatus as defined by claim 13 wherein the carrier member is formed of polytetrafluoroethylene material . 15 15. An apparatus as defined by claim 10, wherein the means for continuously maintaining the binding reservoir material in a substantially airtight relation with the skin surface comprises an airtight, flexible, adhesive cover means. 16. An apparatus as defined by claim 15, wherein the cover means is formed from a material selected from metal foils and impermeable plastic films, and at least a portion of the cover means includes an adhesive coating for adhering to the skin surface. 17. An apparatus as defined by claim 10, further including a removable impermeable cover means covering the portion of the binding reservoir 'material adapted for juxtaposition at the skin surface, which cover is adapted to be removed from the apparatus prior to use for the collection of transdermally migrating vapors. 18. An apparatus as defined by claim 17, wherein the removable cover means is formed from a ' material selected from metal foils and impermeable plastic films.

Inventors: PECK CARL C, PECK, CARL, C.
Applicants: DERMAL SYSTEMS INT, DERMAL SYSTEMS INTERNATIONAL
Application year: 1988
Main classification: A61B5
IPC codes: A61B5, A61B10, G01N33