Surgery – Means for introducing or removing material from body for... – Infrared – visible light – ultraviolet – x-ray or electrical...
Reexamination Certificate
2001-10-17
2004-09-21
Chin, Christopher L. (Department: 1641)
Surgery
Means for introducing or removing material from body for...
Infrared, visible light, ultraviolet, x-ray or electrical...
C604S019000, C604S501000
Reexamination Certificate
active
06795727
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates generally to the field of compound delivery for obtaining both local and systemic results. More particularly, it relates to a non-invasive method of compound delivery through the epidermis by means of increasing the permeability of skin through the use of chemical enhancers and sonophoresis and the synergetic simultaneous use of iontophoresis, electroporation, mechanical vibrations and magnetophoresis for optimizing transcutaneous compound delivery into the body.
The human skin has barrier properties and stratum corneum is mostly responsible for them, thus it is exactly the statum corneum, the outer horny layer of the skin, that imposes the greatest barrier to transcutaneous flux of compounds into the body.
The low permeability attributed to the stratum corneum, a complex structure comprised of multi-layered compact keratinized cells; low permeability is due to dead cells filled with keratin fibers (keratinocytes) surrounded by highly-ordered structure of lipid bilayers (Flynn, G. L., In Percutaneous Absorption: Mechanisms-Methodology-Drug Delivery.; Bronaugh, R. L., Maibach, H. I. (Ed), pages 27-53, Marcel Dekker, New York, 1989).
The stratum corneum hasn't constant thickness, since it depends on each particular area, being thinner in areas subject to folds and much thicker in the hands palms and feet soles, is a very resistant waterproof membrane that both protects the body from invasion by exterior substances and the outward migration of fluids and dissolved molecules and creates a mechanical and biological shield between the environment and the interior of the body. The stratum corneum is continuously renewed by shedding of dead cells during desquamation and the formation of new corneum cells by the keratinization process.
Considering the permeation of compounds with non-charged molecules into the skin the flux of said compound across the epidermis is controlled by Fick's First Law which states that this flux depends on the diffusion coefficient and on the gradient of concentration of the compound. One important issue to be remebered is that the diffusion coefficient is strongly dependent on the degree of hydration of the skin, significantly increasing with it.
Therefore one of the ways of enhancing the flux of compounds into the body is through the so-called penetration or chemical enhancers which increase the coefficient of diffusion of the stratum corneum and may be associated with sonophoresis, that is, ultrasound energy.
From the physical standpoint ultrasound waves have been defined as mechanical pressure waves with frequencies above 20 KHz, H. Lutz et al., Manual Of Ultrasound 3-12 (1984), are generated by either natural or synthetic materials that show the so-called piezoelectric property, meaning that these materials both generate an electric field when mechanically stressed (direct piezoelectric effect) and also generate a mechanical force when an electric field is conveniently applied to them (inverse piezoelectric effect).
These properties have been first established by Pierre and Jacques Curie who have observed their ocurrence in natural materials like the Rochelle salt; however in our days synthetic piezoceramic materials are preferred instead due to their more stable properties since they are not hygroscopic and also to the possibility of being manufactured in any shape, allowing a lot of different applications.
Ultrasound has also been used to enhance permeability of the skin and synthetic membranes to compounds and other molecules and its use to increase the permeability of the skin to compound molecules has been called sonophoresis or phonophoresis meaning transportation through sound like waves.
U.S. Pat. No. 4,309,989 to Fahim describes a method of topically applying an effective medication in an emulsion coupling agent by ultrasound. More particularly, a method of treating a skin condition by applying a medication in an emulsion coupling agent and massaging it into the affected area with ultrasonic vibrations thereby causing the medication to penetrate into the skin. Specifically, a method and composition for the treatment of Herpes Simplex Type 1 and Type 2 lesions. Also specifically, a method and composition for the treatment of demidox mites. U.S. Pat. No. 4,372,296 to Fahim similarly describes treatment of acnes by topical application of zinc sulfate and ascorbic acid in a coupling agent.
U.S. Pat. No. 4,767,402 to Kost et al. discloses a method using ultrasound to enhance permeation of molecules through the skin and into the blood stream, at a controlled rate. Depending on the compound being infused through the skin, the rate of permeation is increased as well as the efficiency of transfer. Drugs which may not be effective under other conditions, for example, due to degradation within the gastrointestinal tract, can be effectively conveyed transdermally into the circulatory system by means of ultrasound. Ultrasound is used in the frequency range of between 20 KHz and 10 MHz, the intensity ranging between 0 and 3 W/cm.sup.2. The molecules are either incorporated in a coupling agent or, alternatively, applied through a transdermal patch.
U.S. Pat. No. 4,780,212 to Kost et al. teaches use time, intensity, and frequency control to regulate the permeability of molecules through polymer and biological membranes. Further, the choice of solvents and media containing the molecules also affects permeation of the molecules through the membranes.
U.S. Pat. No. 4,821,740 to Tachibana et al. discloses an endermic application kit for external medicines, which comprises a drug-containing layer as provided near an ultrasonic oscillator. The kit includes a cylindrical fixed-type or portable-type and a flat regular-type or adhesive-type, and the adhesive-type may be flexible and elastic. The drug absorption is ensured by the action of the ultrasonic waves from the oscillator and the drug release can be controlled by varying the ultrasonic wave output from the oscillator.
U.S. Pat. No. 5,007,438 to Tachibana et al. is described an application kit in which a layer of medication and an ultrasound transducer are disposed within an enclosure. The transducer may be battery powered. Ultrasound causes the medication to move from the device to the skin and then the ultrasound energy can be varied to control the rate of administration through the skin.
U.S. Pat. No. 5,115,805 to Bommannan et al. discloses a method for enhancing the permeability of the skin or other biological membrane to a material such as a drug is disclosed. In the method, the drug is delivered in conjunction with ultrasound having a frequency of above about 10 MHz. The method may also be used in conjunction with chemical permeation enhancers and/or with iontophoresis. It is informed but not shown that chemical penetration enhancers and/or iontophoresis could be used in connection with the ultrasound treatment.
U.S. Pat. No. 5,444,611 to Eppstein et al. describes a method of enhancing the permeability of the skin or mucosa to a biologically active permeant or drug utilizing ultrasound or ultrasound plus a chemical enhancer.
Ultrasound can be modulated and frequency modulated ultrasound from high to low frequency can develop a local pressure gradient directed into the body. The method is also useful as a means for application of a tatoo by nininvasively delivering a pigment through the skin surface. Due to the completeness of that disclosure, the information and terminology utilized therein are incorporated herein by reference.
U.S. Pat. No. 6,041,253 to Kost et al. describes a method for transdermal transport of molecules during sonophoresis (delivery or extraction) further enhanced by application of an electric field, for example electroporation of iontophoresis. This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field. Due to the completeness of that disclosure
Chin Christopher L.
Lam Ann Y.
Moazzam & Latimer LLP
LandOfFree
Devices and methods for promoting transcutaneous movement of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Devices and methods for promoting transcutaneous movement of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Devices and methods for promoting transcutaneous movement of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3271447