ES2617525T3 - Swivel heat exchanger - Google Patents

Abstract

A rotating abrasive device (10) comprising: a housing (32) comprising at least one housing element, wherein said at least one housing element is selected from the group consisting of an upper housing, a lower housing, an internal housing , an external accommodation, and combinations thereof. at least one housing element adapted to rotate; at least one matrix of microprotrusions (14) adapted to alter the skin of a subject when it is rotated; a mechanical rotating means for mechanically rotating said at least one microprotrusion matrix (14) against the skin of a subject with sufficient force to substantially alter and penetrate the cornea layer of the subject without perforating said cornea layer.

Description

DESCRIPTION

Substance administration through a rotating microabrasive system

Related Requests

The present application claims priority of US provisional patent application No. 60 / 406,694, filed on August 29, 2002, which is incorporated herein in its entirety by this reference. This 5 application is also related to US Application Serial No. 10 / __________ (file of representative No. P-5369B), and US Application Serial No. 10 / __________, (file of representative No. P- 5370]

Field of the Invention

The present invention relates to a device for scraping the skin. More particularly, the invention relates to a device that imparts a rotating movement to an abrasive surface.

Background of the invention

The administration of substances to the body through the skin has been typically invasive, including needles and syringes to facilitate intradermal (ID), intramuscular (IM) or subcutaneous (SC) injection. These methods are painful for the subject, need the skill of a trained professional and usually cause bleeding. 15 efforts have been made to overcome these disadvantages by using devices that scrape the corneal layer, the thin outer layer of keratinized cells about 10-20 pm thick. The bioactive substance is administered to the exposed viable epidermis.

This technique avoids the nervous network and places the bioactive substance very close to the blood vessels and lymph nodes for absorption and administration of the substance throughout the body. twenty

For topical administration of vaccines, the epidermis itself is a particularly desired objective since it is rich in cells that have antigen. In comparison, the dermal layer under the epidermis contains fewer cells that have antigen. In addition, the corneal layer and epidermis do not contain nerves or blood vessels, so this method has the advantage of being essentially painless and free of blood while giving access to skin layers capable of responding to the antigen. 25

The prior art reports a variety of devices and methods to alter the corneal layer in order to administer substances to the body. For example, the corneal layer can be broken by perforating as reported in US Patent 5,679,647 to Carson, et al. This patent informs that small diameter spikes, such as those found in devices used for tuberculin skin tests and allergy tests, can be coated with polynucleotides or oligonucleotides and used for the administration of such materials in the skin. The method of using such devices involves piercing the skin with the barbs resulting in intracutaneous injection of the coated substance.

U.S. Patent 5,003,987; U.S. Patent 5,879,326; and U.S. Patent 3,964,482 describe the corneal layer by cutting.

WO 02/02180 A2 describes an apparatus for administering or removing a substance from a patient that includes a support member 35, a device for piercing the skin and an advance assembly for advancing the device for piercing the skin to an operative position.

Compendium of the invention

The subject of the invention is defined by claim 1.

The present invention relates to a method and device for rotating abrasion of the skin and particularly of the corneal layer of the skin. The invention further relates to a method of obtaining a sample of or for the administration of a substance to the skin, such as a drug or pharmaceutical agent, through the rotating abrasion of an area in the corneal layer.

The substances to be administered include particularly bioactive substances, including pharmaceutical agents, medicaments, vaccines and the like. The substances may be in solid or liquid form, depending on the method of administration and formulation. They can be administered, among others, in the form of dry powders, gels, solutions, suspensions and creams. Particularly preferred medications for administration with the methods of the invention include vaccines, allergens and gene therapeutic agents.

One aspect of the invention relates to a method and device for preparing a site of administration in the skin to enhance the administration of a pharmaceutical agent through the corneal layer of the skin at a sufficient depth where the pharmaceutical agent can absorb it. and use the body. Said preparation is achieved by using a device to impart a rotational movement to the total microabrasive device or the abrasive surface of

a microabrasive device to alter the corneal layer.

The dermal tissue represents an attractive target site for the administration of vaccines and gene therapeutic agents, in the case of vaccines (both gene and conventional), the skin is an attractive administration site due to the high concentration of antigen-presenting cells (APC ) and APC precursors found within this tissue, especially Langerhan epidermal cells (LC). Several gene therapeutic agents are designed for the treatment of skin disorders, skin diseases and skin cancer. In such cases, direct administration of the therapeutic agent to the affected skin tissue is desired. In addition, skin cells are an attractive target for gene therapeutic agents, of which one or more encoded proteins are active in distant sites of the skin. In such cases, skin cells (for example, keratinocytes) can function as "bioreactors" that produce a therapeutic protein that can be rapidly absorbed into the systemic circulation 10 through the papillary dermis. In other cases, direct access of the vaccine or therapeutic agent to systemic circulation is desired for the treatment of distant skin disorders. In such cases, systemic distribution can be achieved through the papillary dermis.

The present invention provides a microabrasive device for rotationally scraping the skin together with the administration of a bioactive substance, including non-taxatively, nucleic acids, amino acids, derivatives of 15 amino acids, peptides or polypeptides. It was found that nucleic acids show enhanced gene expression and produce an enhanced immune response to the expressed protein when administered simultaneously with abrasion of the corneal layer. Similarly, allergens administered simultaneously with abrasion produce a more vigorous immune response than conventional allergen test methods.

In a preferred embodiment, the present invention comprises a microabrasive for administering a substance in the skin having a base with at least one abrasive facet, with which an abrasive surface having an arrangement of microprotrusions having at least one scraping edge is attached, mounted or integrated, and a handle joining facet, with which a handle or other gripping device joins, mounts or integrates. The handle can also be separated from, joined with or integrated with a mechanism capable of imparting a rotating movement to the total device or only the abrasive surface thereof. "Abrasive surface" refers to the surface that is presented to the skin during the abrasion process, which includes at least one microprotusion, the surface area between said one or more microprotrusions and surrounding surface.

A circular or rotating abrasion of the skin can be achieved with a mechanically or externally actuated rotating device that includes a microabrasive device so that a localized area of skin is treated or scratched. The rotating device would comprise a housing in which the microabrasive matrix is rotated against the skin of a subject and an interlocking mechanism that the user would deactivate to drive the rotation of the rotating device. In one embodiment, the housing of the rotating device would keep the skin in place as pressure is applied to ensure that the microabrasive matrix surface would scrape and / or strain the same area of a patient's skin and a spring or other component. associated with the interlocking mechanism would control the speed at which the abrasive surface rotates against the skin. Therefore, this embodiment would ensure consistent and reproducible results in terms of the amount of substance absorbed within a body, especially in a clinical setting.

According to another embodiment of the invention, circular abrasion according to one method can be combined with monitoring the amount of pressure applied to the microabrasive device (either visually or in a rotating device) to maintain a constant downward force. approximate to achieve a more consistent abrasion, and more effectively administer drug, vaccine or medication to a patient's body. For example, the technician and / or user can monitor the downward force that is applied to the microabrasive device during the rotating movement so as to apply an appropriate downward force. Then, the technician using the microabrasive device can apply the pressure necessary to achieve the same degree of corneal layer alteration and penetration depth in all patients. This may be especially important for the administration of certain classes of compounds, such as vaccines, in which the desired target area is the cells that have antigen within the epidermis and not the deepest dermal tissue and capillary beds.

Pressure monitoring can be achieved by a mechanical or electrical pressure gauge, a prestressed spring or an electronic pressure transducer. This monitoring device can be simple as indications or sophisticated as an electronic piezoelectric film that detects the amount of pressure and indicates the amount of pressure. fifty

A method for administering a substance to the skin is also described, which comprises the use of a device that imparts a rotating movement to the microabrasive device or microabrasive surface in an area of the skin to produce grooves of sufficient depth to allow the substance, which it is administered before, simultaneously with, or after the abrasion of the skin, be absorbed by the predetermined skin layer. By means of the present microabrasive device the rotating movement combined with multiple passes of the device through the skin 55 can result in progressively deeper grooves in the skin, thus allowing the administration of a substance at a desired depth in the skin.

Brief description of the drawings

The invention is more clearly understood after reading the following detailed description with reference to the attached figures, where reference numbers refer to similar elements throughout the present and where:

Figure 1 is a side view of a microabrasive that can be applied manually; 5

Figure 2 is an enlarged side view of an abrasive surface for an abrasive matrix according to an embodiment of the invention on the skin of a patient;

Figure 3 is a cross-sectional side view of an abrasive surface;

Figure 4 is a photomicrograph of an abrasive surface;

Figure 5 is a bottom view of the abrasive surface of the embodiment of Figure 3; 10

Figure 6 is a partially cross-sectional perspective view of skin scraped grooves;

Figure 7 illustrates a rotary delivery device containing abrasive surfaces;

Figure 7E is an enlarged cross-sectional view of a movable rod and hollow sleeve of a rotating device according to an embodiment of the invention.

Figure 8 illustrates a cross-sectional view of the rotating device of Figure 7; fifteen

Figure 9 is a schematic view of a portion of another embodiment of a rotary delivery device containing a safety retraction feature;

Figure 10 is a schematic close-up view showing a stop in the device of Figure 9;

Figure 11 is a schematic cross-sectional view of another embodiment of a rotating microabrasive;

Figure 12 is a cross-sectional perspective view of the internal and abrasive end of the device of Figure 11; twenty

Figure 13 illustrates the abrasive surface assembly of the device of Figures 11 and 12;

Figure 14 illustrates the inside of the rear stock of the device of Figures 11 and 12; Y

Figure 15 is a second perspective view of the abrasive surface assembly of Figure 13.

Detailed description of the invention

The primary skin barrier properties that include resistance to drug or vaccine administration reside in the outermost layer of the epidermis, called the cornea layer. The inner layers of the epidermis generally include three layers, commonly identified as granular layer, Malpighi layer and basal layer. Once the drug or vaccine or other substance appears below the corneal layer, there is essentially no resistance to diffusion in subsequent layers of the skin and final absorption by the body.

The administration of a substance in or through the viable epidermis can be an effective method to facilitate the absorption of some substances, and particularly some vaccines, by the body. The present invention relates mainly to a device and method for facilitating the administration of a substance, and particularly a pharmaceutical agent, into or through the viable epidermis so that it results in faster absorption of larger amounts of the bioactive substance or pharmaceutical agent.

As used herein, the term "scraping" refers to removing at least a portion of the corneal layer to increase skin permeability without causing excessive skin irritation or compromising the skin barrier to infectious agents. This is contrary to "piercing" that produces specific holes through the corneal layer with areas of corneal layer unaltered between the holes.

As used herein, "penetrate" refers to entering the cornea layer without completely passing through the cornea layer and entering adjacent layers. This does not mean that the corneal layer cannot be fully penetrated to reveal the interface of the underlying skin layer. On the other hand, perforation refers to passing through the corneal layer completely and entering adjacent layers below the corneal layer.

The present invention relates to a device and a method for scraping the cornea layer in a rotating or circular manner to scrape the cornea layer to enhance the administration of a substance through the cornea layer of a patient's skin. Four. Five

The rotating method and the device for rotating a microabrasive matrix surface according to the invention is

capable of scraping the skin to increase the surface area within the epidermis layer and improve the effectiveness of the administration of substance or drug or vaccine in the body of the subject by direct absorption by cells presenting antigen (APC), drainage capillary, or the phenomenon of lymphatic drainage. In preferred embodiments, the device is capable of scraping the skin thus penetrating the cornea layer without piercing the cornea layer.

Preferably, an abrasive surface comprising a desired matrix of microprotrusions is rotated against a desired skin area. The resulting circular abrasion of the skin according to the invention alters the corneal layer that increases the surface area of the viable epidermal layer so that a greatly increased dose concentration of the administered substance is achieved. Controlled circular motion and abrasion tend to keep the dose within the rotating or circular scraped area. Therefore, the dose can be limited to a smaller area using the circular or rotary administration according to the invention resulting in the increased substance administered to a limited portion of the body, since the substance is not pushed out of the site of application. For example, the substance may be contained in a 1cm2 circle according to an embodiment of the invention. That is, the scraped area using a substantially straight technique, forward and backward, can be about 4 times larger than a scraped area using a circular technique. Depending on the subject or the substance administered, a larger or smaller abrasive area can be used and can be circularly administered and a smaller area will be scraped than with the same abrasive surface as when using a straight technique.

The substance to be administered using the methods of the invention can be applied to the skin before abrasion, simultaneously with abrasion or after abrasion. According to an embodiment of the methods of the invention, however, certain or specific bioactive substances, including nucleic acid-based vaccines and peptides or polypeptides, are applied to the skin before or simultaneously with abrasion rather than applied to skin. 20 previously scraped. That is, certain substances when scraped on the skin instead of passively applied to previously scraped skin result in an improved response.

The substance can be administered to the skin in any pharmaceutically acceptable way. In one embodiment, the substance is applied to the skin and an abrasive device is then forced against the skin while rotating or circularly moving on the skin and the substance. It is preferred to use the minimum amount of downward force to produce the abrasion 25 that achieves the desired result. The amount of force and rotation to achieve the abrasion necessary to achieve effective administration depends on the drug or vaccine to be administered. One skilled in the art will be able to determine the appropriate amount of force and rotation (and then, the resulting abrasion) to achieve the appropriate amount of drug or vaccine administration through routine experimentation.

In one embodiment, the substance can be applied dry to the abrasive surface or a surface adjacent to it or even contained within a storage tank of, or within the delivery device before application. In this embodiment, a reconstitution liquid may be applied to the skin at the site of administration before or simultaneously with the application of the abrasive device coated with substances. The abrasive surface is then rotated against or rubbed circularly on the skin so that the subsequent substance or simultaneously dissolves in the reconstitution liquid on the skin surface and is administered simultaneously with abrasion. Alternatively, a reconstitution liquid may be contained in the abrasive device and released to dissolve the substance as the device is applied to the abrasion skin. Due to the containment of the abrasive in a smaller area when a circular abrasive movement is used, the volume of reconstitution liquid can also be reduced, depending on the needs of the substance to be applied.

According to the invention, the skin alteration, for example, grooves or other openings, will be circularly formed in the skin of a subject. If the abrasive surface area of the microabrasive is composed of a rectangular, square or other matrix of microprotrusions that results in crossed grooves when the microabrasive device is rotated or rotated, this intersection of grooves suggests that the reconstitution fluid will have more grooved areas inside of the scraped area and then can minimize the amount of liquid that is lost due to the centrifugal force of the rotating microabrasive abrasive surface. In addition to the greater number of grooves in the abrasive skin, a more tortuous path is created that also suggests that the liquid tends to remain in the scraped area. Then, the circular abrasion method can use a smaller volume of reconstitution liquid and suggests a reduction of substance loss since the scraper will form grooves that capture the substance and possibly present an increased surface area to absorb the substance, thus preventing leakage. of the substance as is known in the prior art of abrasive methods. fifty

As shown in Figure 1, a manual microabrasive device 2 includes the base 4 on which an abrasive surface 5 can be mounted. Preferably, the base 4 is a solid molded part. In one embodiment, the base 4 is configured with a mushroom crown 4b that curves upward and is truncated at the top. The upper part of the base 4 is generally flat with an abrasive surface 5 mounted there. Alternatively, the truncated upper part may have a groove to receive the abrasive surface 5. In all embodiments, the abrasive surface 5 includes a platform 12 with a microprotrusions matrix 14 (Figure 3) that are held or otherwise they extend above platform 12.

With reference to Figure 2, in one embodiment of the microabrasive device 10, it is not shown, of the invention, includes an abrasive surface support adapted 12 with a plurality of microprotrusions 14 extending from the bottom surface of the support. The support is generally thick enough to allow the union of the 60

surface to the base of the microabrasive device Alternatively, a different microabrasive device 10 may be joined with or be an integral part of the upper surface of the abrasive surface support 12. The dimensions of the abrasive surface support 12 may vary depending on the length of the microprotrusions, the amount of microprotrusions in a given area, the three-dimensional contour (flat, stepped, lenticular, arched, etc.) of the microprotrusions, the amount of the substance to be administered to the patient's skin 28, and the device 5 microabrasive with which it is attached or forms an integral part. Typically, the abrasive surface support 12 has a surface area of about 1 to 4 cm2. In a preferred embodiment, the abrasive surface support 12 has a surface area of about 1 cm 2.

As shown in Figures 2, 3, 4 and 5, the microprotrusions 14 project from the surface of the abrasive surface support 12 and are substantially perpendicular to the plane of the abrasive surface support 12. The 10 microprotrusions in the illustrated embodiment are arranged in a plurality of rows and columns and separate at a uniform distance. Alternatively, the microprotrusions can be separated non-uniformly in a pattern, or they can be separated randomly. The microprotrusions 14 of one embodiment, have a generally pyramid shape with sides 16 that extend to a tip 18. The sides 16 as shown have a generally concave profile when viewed in cross-section and form a curved surface that extends 15 from the abrasive surface support 12 to the tip 18 '. In the illustrated embodiment, the microprotrusions are formed with four sides 16 of substantially the same shape and dimension. As shown in Figures 4 and 5, each of the sides 16 of the microprotrusions 14 has adjacent opposite side edges with an adjacent side and form a scraping edge 22 extending outwardly from the abrasive surface support 12. The edges scrapers 22 define a generally triangular or trapezoid scraper surface 20 corresponding to the shape of side 16. In other embodiments, microprotrusions 14 can be formed with fewer or more sides.

The microprotrusions 14 preferably end in blunt tips, or plateau 18. Generally, the plateau 18 is substantially flat and parallel to the support 14. When the microprotusion base is wider than the tip 18, the total length of the microprotrusions does not penetrate the skin; then, the length of the microprotrusions is greater than the total depth to which said microprotrusions penetrate said skin. The plateau 18 preferably forms a well-defined sharp edge 20 where it reaches the sides 16. The edge 20 extends substantially parallel to the abrasive surface support 12 and defines an additional scraping edge. In other embodiments, the edge 20 may be somewhat rounded to form a smooth transition from the sides 16 to the plateau 18. Preferably, the microprotrusions have a frustoconic or frustopyramidal shape. 30

The microabrasive device 10 and the microprotrusions can be formed with a plastic material that does not react with the substance administered. A non-taxable list of suitable plastic materials includes, for example, polyethylene, polypropylene, Polymethyl methacrylate (PMMA), polyamides, polystyrenes, polyesters, and polycarbonates as is known in the art. Alternatively, the microprotrusions can be formed with a metal such as stainless steel, tungsten steel, nickel alloys, molybdenum, chromium, cobalt, titanium, and alloys thereof, or other materials such as silicon polymers, ceramics and glass. Metal microprotrusions can be manufactured using several techniques similar to photolithographic etching of a silicon wafer or micromachining using a diamond-tipped mill as is known in the art. Microprotrusions can also be made by photolithographic etching of a silicon wafer using standard techniques as is known in the art. They can also be manufactured in plastic by an injection molding process, as described, for example, in US Patent Application 40 Serial No. 10 / 193,317, filed July 12, 2002.

The length and thickness of the microprotrusions are selected based on the particular substance that is administered and the thickness of the corneal layer at the location where the device will be applied. Preferably, the microprotrusions penetrate the cornea layer substantially unperforated or pass through the cornea layer. The microprotrusions can have a length of up to about 500 microns. Suitable microprotrusions 45 have a length of about 50 to 500 microns. Preferably, the microprotrusions have a length of about 50 to about 300 microns, and more preferably in the range of about 150 to 250 microns, more preferred is 180 to 220 microns. The microprotrusions in the illustrated embodiment have a generally pyramidal shape and are perpendicular to the plane of the device. These shapes have particular advantages to ensure that abrasion occurs at the desired depth. In preferred embodiments, the microprotrusions are 50 solid members. In alternative embodiments, the microprotrusions may be hollow.

As shown in the embodiment of Figures 3 and 5, the microprotrusions 14 are uniformly separated into rows and columns to form a matrix to contact the skin and penetrate the corneal layer during abrasion. The spacing between the microprotrusions may vary depending on the substance that is administered either on the surface of the skin or within the skin tissue. Typically, the rows of microprotrusions are separated to provide a density of about 2 to about 10 per millimeter (mm). Generally, the rows or columns are separated at a distance substantially equal to the spacing of the microprotrusions in the matrix to provide a microprotusion density of about 4 to about 100 microprotrusions per mm2. In another embodiment, the microprotrusions can be arranged in a circular pattern. In yet another embodiment, the microprotrusions can be arranged in a random pattern. When arranged in columns and rows, the distance 60 between the centers of the microprotrusions is preferably at least twice the length of the microprotrusions. In a preferred embodiment, the distance between the centers of the microprotrusions is twice that of

the length of the microprotrusions ± 10 microns. A wider spacing is also included, up to 3, 4, 5 and larger multiples of the length of the microprotrusions. In addition, as noted above, the configuration of the microprotrusions may be such that the height for the microprotrusions may be greater than the depth in the skin that these protrusions will penetrate.

While Figure 4 shows a partial microprotrusion matrix of abrasive surface 5, it is contemplated that an abrasive surface may be composed of a plurality of microprotrusion matrices. For example, four matrices of rectangular or square microprotrusions can be used to make an abrasive surface. In one embodiment, the microprotrustion matrix can be constructed with several smaller microprotrusion matrices so that the scraper edges 20 and 22 of each smaller microprotrusion matrix face a different direction in the larger composite microprotrusion matrix. Asymmetrically opposite scraping edges 10 (or scraping edges at different angles) can maximize abrasion by always presenting a scraping edge during rotation of the abrasive surface. A larger microprotrusions matrix composed with this feature can be achieved by making a frustoconic microprotrusions matrix where the scraping edges are formed along the crystalline axis with the same orientation and then cutting the resulting frustoconic microprotrusions matrix into a smaller number of matrices. and rotating the smaller matrices so that the scraping edges have a different orientation from the adjacent smaller matrix. To provide an abrasive surface that matches the skin contour, each matrix of the abrasive surface can have varying microprotrusions heights to give a flexible platform effect while the abrasive surface is rotated.

The abrasive surface 5 can be rectangular, circular or can have any other shape. Depending on the drug or vaccine to be administered and the amount of abrasion desired, the microprotrusion matrix 14 on the abrasive surface 20 may have varied designs that may be beneficial for rotating delivery devices. The tips of the microprotrusions may be in the same plane or their heights may vary due to the amount of abrasion desired. Each microprotrusion has at least one scraping edge and has a length to penetrate the corneal layer with perforation of the corneal layer, and depending on the desired amount of abrasion, the scraping edges of a matrix or portion of a matrix may point to them or different directions. 25

The flat top surface or plateau of the frustoconic or frustopyramidal microprotrusions is generally 10 to 100, preferably 30-70 and more preferably 35-50 microns wide.

The manual microabrasive device 2 of Figure 1 is applied to a subject by gripping the handle 6 and moving the abrasive device 2 through the skin of a subject 28 with sufficient pressure to allow the abrasive surface 5 to penetrate the outer protective skin or the cornea layer of the subject. The pressure applied to the base causes the surface 5 30 and the base 4 to be pressed into the subject's skin. Therefore, it is preferred that the height of the inclined mushroom crown 4b be sufficient to prevent an applied substance from flowing over and to the lower side 4c of the base 4 when the microabrasive device 2 is used.

A handle 6 is attached to the arched base 4. The handle 6 can be glued (for example with epoxy) to the lower side 4c of the base 4, it can be adjusted quickly or by friction, or it can be molded integrally. The lower side 4c of the base 35 4 may be flush with the fungus crown 4b or it may extend beyond the fungus crown, or it may be formed integrally as an extension of the base 4. The lower side 6b of the handle 6 is wider than the axis of the handle 6. The lower side 6b includes an impression 6d that serves as a support for a person who administers the substance to firmly grasp the microabrasive device 2. In addition, the protrusions 8 are formed in the part outside of the handle 6 to help the user to firmly grip the handle 6 when the device 2 is used against the patient's epidermis.

The handle 6, as well as the base 4, of the microabrasive device 2 is preferably molded with plastic or similar material. The microabrasive device 2 is preferably manufactured economically so that the total microabrasive device and the abrasive surface can be placed after use in a patient.

One method of forming an abrasive surface with microprotrusions is to engrave a rectangular piece of silicon. The etching process provides a master abrasive surface with a surface contour. As described below, the master abrasive surface can be converted into a mold for an abrasive surface with a microprotrusion matrix. The surface contour of the master is coated with a layer of material, the layer preferably has a thickness of at least about 0.254 - 5.08 mm (0.01 - 2 inches) and preferably 1,778 mm (0.07 inches) or more. The teacher is removed from the material layer to form a negative image of the teacher in the material layer. The negative image can then be used in a molding process to form a positive image with features that are substantially equal to the teacher's features.

The teacher is sacrificed when removed from the material layer. For example, the teacher can be removed by engraving. In another embodiment, the master is coated with a release layer, before being coated with the material layer. The release layer facilitates the removal of the teacher from the negative image, keeping the teacher 55 unharmed.

Another method of forming an abrasive surface with a plurality of microprotrusions involves using a master abrasive surface with a surface contour that defines a plurality of features. The surface contour is the

Master is coated with at least one layer of material to form a cover. The teacher is removed from the deck to form a negative image of the surface contour on the deck. The negative image on the cover is substantially filled with material, for example, polycarbonates (LEXAN® polycarbonate), acrylics (ACRYLITE® acrylic), COC (Topas® cyclic olefin copolymers), polystyrenes, or other suitable structural plastic, to form a device with features substantially equal to those of the teacher. Of course, other types of materials 5 can be used to fill the cover. The negative image can be filled using injection molding, compression molding, etching or any other compatible technique.

In a further embodiment, the cover defines gaps with a depth of about 5 microns to about 250 microns. The gaps can be arranged in an array of rows and columns or other uniformly spaced or non-uniformly spaced patterns, including random patterns, to provide a density of about 10 to about 100 of the gap per mm2. The cover is a negative or inverse image for the molding of the teacher's features, where the teacher can have gaps or peaks in its surface contour ranging from about 0.5 microns to several hundred microns in length.

As described above, a method of administering a substance to a patient's skin may include the steps of coating a patient's outer skin layer with a medication or other substance and turning the microabrasive device 15 against the patient's skin to provide abrasions leaving enough grooves to allow the substance to enter the patient's epidermis. Alternatively, the medicament or other substances can be applied to the abrasive surface 5 of the microabrasive device 2. Rotation is achieved mechanically or electronically with a device (Figures 7-15) that rotates the microabrasive surface as described in continuation. The rotation can be done in the clockwise or counterclockwise direction or in both directions. twenty

In preferred embodiments of the microprotrusions, the upper surfaces or edges 20 (Figures 2, 3, 4 and 5) of the microprotrusions 14 scrape the outer protective skin layer by penetrating the corneal layer that forms grooves 26 (Figure 6) thus allowing the medication or other substances enter the patient. In addition to the edges 20, the edges 22 of the microprotrusions 14 also form scraping edges to help form the grooves 26 or grooves in the skin 28. As shown in Figure 6, depending on the amount of microprotrusions 14 and their arrangement on the abrasive surface 5, the scraping edges 20 and 22 form open valleys 25 and scarified side walls 27 in the grooves 26. After the initial abrasion of the outer protective skin layer in a first circular direction, the exit and entry edges of the microabrasive device 2 can also rub the surface of the scraped area leading to the drug or substance within the area of scraped skin thus improving its interaction with the underlying epidermis. 30

As for Figures 7 and 8, a rotary delivery device 30 according to an embodiment of the invention is shown. Figure 7 is a perspective view of a device shown with a transparent housing so that the mechanical components can be seen, while Figure 8 is a sectional view of the rotating device 30. The rotating administration device 30 includes a housing 32, which is cylindrical in this preferred embodiment. The housing should not be circular, since rectangular, 35 square, oval or other shapes can be used. The housing 32 has a longitudinal axis, is generally hollow and preferably has a shape around which the fingers of a user can be grasped for greater control. The upper part 34 of the housing 32 has an opening 36 through which an interlocking mechanism, such as the button 38 which is integrally attached to a longitudinally movable bar 38 ’moves after activation. In a preferred embodiment, the upper part of the button 38 extends through the opening 36 while a base 37 of the adjacent bar 40 '38 of the button 38 is located within the housing 32. The base 37 has a width / diameter greater than the top of the base. The width / diameter of the base is approximately equal to the inside of the housing 32. The thickness of the base 37, as well as its width, is designed to provide a strong and stable support for the activation means or push button 38. The bar 38 'preferably it is integrally connected with the base 37 of the button 38 inside the housing 32. 45

The other end 39 of the rotary delivery device 30 is designed to be placed against the skin of a subject and to remain fixed while the button 38 is activated. Then, the end 39 of the housing 32 serves to tighten the skin of a subject before the abrasion by an abrasive surface 5. That is, the perpendicular force applied to the rotary delivery device provides an area of tight skin to aid the abrasive surface when scraping the skin area. fifty

Concentrically located within the housing 32 and preferably grooved from the end 39 of the rotary delivery device is a hollow handle 40. The hollow handle 40 can be freely rotated within the housing 32 and is formed with groove-type threads. The end of the longitudinally movable bar 38 'opposite to the end attached to the button 38 is inserted into the upper end of the hollow handle 40. The projections (not shown) extend from the end of the longitudinally movable bar 38' extend within the grooved threaded areas 55 of the hollow handle 40. The threads are designed to transfer the longitudinal movement of the button 38 and the bar 38 'within a rotating movement. Alternatively, the opposite end of the bar 38 ’could be provided with a recess and the hollow handle 40 could have raised threads to transfer the longitudinal movement of the bar 38’ to the desired rotating movement. As a result of this structure, when the button 38 is activated, the bar 38 'collapses inside the hollow handle 40 along the grooves of the thread thus causing the hollow handle 40 to rotate approximately 360 degrees through the total displacement of the button 38.

An end face 42 is formed integrally at the end of the hollow handle 40 near the end 39 of the rotary delivery device 30. In an alternative embodiment, an end face can be joined by adhesive or the like with the hollow handle 40. A abrasive surface 5, as previously described, joins with a front end 44 of the face 42 of the hollow handle 40. The abrasive surface 5 can be retracted into the housing 32 before pressing or activating the button 38. The curved portion of The groove type threads can be designed so that the abrasive surface 5 rotates approximately 360 degrees against the subject's skin when the button 38 is pressed. Depending on the drug or vaccine to be administered, it may be convenient to have less rotation or multiple rotations of the abrasive surface Since the housing 32 remains fixed while the button 38 is activated, the housing 32 keeps the skin in place as the abrasive surface 5 scratches the skin area inside the fixed housing 32. Therefore, consistent results should be achieved. and reproducible in terms of the amount of drug or vaccine absorbed by a patient.

Figure 7E illustrates an embodiment according to the invention wherein the end of the bar 38 'and the top of the hollow handle 40 are designed to provide a safety retraction feature. The upper part of the hollow handle 40 is provided with a projected flange 48 and the end of the bar 38 'is provided with two projected flanges 49 that are spaced apart. After the rotating administration device has sufficiently scraped the desired skin area, an operator pulls the button 38 of the housing 32 causing one of the projected flanges 49 of the bar 38 'to move past the projected flange 48 of the hollow handle 40 so that the projected flange 48 rests between the two spaced projected flanges 49 of the bar 38 '. In this way, the hollow handle is pulled back into the housing 32 and locked in its retracted safety position, since great force would be necessary to move the hollow handle from the retracted safety position. This feature can also be used to push the device into the skin, as well as to remove it.

While the interlocking mechanism illustrated is a button positioned perpendicular to the abrasive surface, other interlocking mechanisms can be used. For example, a lever placed around the housing of the rotating device can be pushed approximately parallel to the skin that is held in place by the fixed housing. When the lever is pushed sideways, a spring is deactivated causing the abrasive surface 25 that is held inside the fixed housing to rotate. Similarly, a handle that projects from the side of the fixed housing may have a lever, button or rotating movement that deactivates the spring causing the abrasive surface 5 to rotate.

The abrasive surface 5 can be attached to the front end 44 of the hollow handle 40 by means of an intermediate ring 45, as shown in Figure 8 or can be attached directly to the front end 44 of the hollow handle 40 by adhesive (Figure 7). Depending on the positioning of the threads in the hollow handle 40, the abrasive surface 5 may move somewhat forward towards the front of the housing 32. That is, the abrasive surface 5 would retract into the housing until the button 38 is activated. Then, a As the bar 38 'collapses inside the hollow handle 40, the hollow handle 40 and the abrasive surface 5 are pushed forward and rotated due to the threaded hollow handle. Then, as the button 38 is pressed, the abrasive surface 5 rotates against the subject's skin. The abrasive surface 5 can be permanently attached with a disposable piece or, the abrasive surface can be placed in a part that can be split on the ring 45 or other disposable piece. This will allow the part to be replaced without having to reproduce the total rotary delivery device. In another embodiment, the abrasive surface 5 can also be an integral part with the end face 42 attached to the hollow handle 40. In said embodiment, the total rotary delivery device can be discarded after the abrasion of a single patient. It is believed that the rotary delivery device 30 scratches more than one location in a single patient to administer a vaccine or other substance and then can be discarded. It is also believed that the rotating device is modified to accommodate or otherwise coincide with or accept a separate microabrasive device instead of having the abrasive surface 5 as an integral part there.

A light spring 46, for example an OD cable of 0.024 "and 5 windings per inch, concentrically surrounds the bar 45 38 'and the hollow handle 40. As shown in Figure 8, the end face 42 of the hollow handle 40 has a projected edge 43 and light spring 46, in its extended state, extends from the projected edge 43 to the base 37. Pressing the button 38 compresses the spring 46 so that the device 30 automatically restarts when the pressure is removed of the button 38. That is, when the button 38 is no longer pressed thus releasing the spring 46 from its compressed state, the spring 46 applies an opposite load that causes the abrasive surface 5 to rotate 360 degrees in the opposite direction. Button 38 can be pressed a number of times depending on the amount of abrasion desired. This retracted abrasive surface provides a safe disposal feature for the rotary delivery device.

For easy assembly of a rotary delivery device according to the invention, a retaining ring or washer 47 covers the opening 36. In one embodiment, the retaining ring 47 has two pins 47e on opposite sides 55 of the ring, one of which is shown in Figure 7. The pins 47e are received in the grooves 32g in the upper part of the housing 32 and locked in place by rotating them. In another embodiment, the upper part of the housing 32 would be provided with a cover with an opening that receives the button 38. The cover would be threaded onto the housing 32. Then, the spring 46, hollow handle 40, bar 38 'could easily be mounted. and button 38 inside the housing 32 and then lock the assembly together. The retaining ring 47 or a screw cap would hold the previous 60 components inside the housing 32, even when the spring 46 is released. The housing 32, hollow handle 40, bar 38 'and button 38 are made of a plastic material, which can be easily molded into the shapes

private individuals

The shrinkage of the abrasive surface 5 within the housing 32 can be achieved by a cushion layer 50 concentrically formed around the lower end of the bar 38 and the upper end of the hollow handle 40 as shown in Figures 9 and 10. The cushion 50 has a height so that a total displacement of the button 38 can be achieved before the base 37 reaches the top of the cushion 50. A technician who uses the rotary delivery device will feel the resistance of the cushion and this tactile sensation would indicate that the technician should release the button 38 causing the abrasive surface 5 to rotate in the opposite direction. After the appropriate amount of revolutions results in the desired amount of abrasions, the technician would press the button 38 beyond the initial resistance of the cushion 50 so that the projections of the bar 38 'are locked into the recesses 51 in the grooved threads of the hollow handle 40. The cushion 50 then pulls the abrasive surface 5 10 into the housing 32 as a safety feature.

As shown in the enlarged portion of the embodiment in Figure 9, the recess 51 can be located adjacent to the end face 42 at the end of a groove type thread. The light spring 46 surrounds the cushion 50, which is grooved in the housing 32, and extends from a ring flange 45 to the base 37 of the button 38. After the projections of the bar tip 38 'are locked in the holes 51 of the hollow handle 40, the technician could pull the button 15 away from the end 39 thus retracting the hollow handle 40, ring 45 and abrasive surface 5 inside the housing 32. Specifically, the ring flange 45 would be pulled towards the cushion 50 deforming the cushion around the flange resulting in the cushion 50 holding the ring 45 and the abrasive surface 5 inside the housing 32. The cushion material 50 may be foam or the like to provide the feature gear that maintains the abrasive surface withdrawn after the rotational administration of a substance by abrasion in a patient.

Alternatively, it is believed that a second spring (not shown) with a compression force greater than the light spring 46 could be used to allow the button 38 and the bar 38 'locked in the hollow handle 40 to retract into the housing 32. Such an embodiment would allow the rotary delivery device to provide multiple rotations of the abrasive surface and retract into the housing 32. 25

In a preferred embodiment the housing 32 would have a dome flange 32d that can be an integral part with the housing 32. This dome flange would provide stability to the ring 45 so that it does not tilt or tilt during the rotating movement. The second spring can be located outside the light spring 46 with one end at the top of the dome flange 32d and the other end of the second spring extends towards the base 37 in its relaxed state. 30

In another embodiment, the light spring 46 may have a diameter such that one end of the spring reaches the top of the dome flange 32d and the other end extends towards the base 37 in the relaxed state. This embodiment, when used with the cushion retraction feature described above, would result in a rotary delivery device with a retractable feature. Specifically, a technician would press the button 38 leading to the bar 38 'along the groove-type threads of the hollow handle 40 causing the hollow handle 40 and the abrasive surface 35 to rotate. The projections of the bar 38 'would be pushed into the recesses 51 by locking the hollow handle 40 with the bar 38'. When the technician stops applying pressure to the button 38, the spring 46 would expand into its relaxed state causing the abrasive surface 5 and the hollow handle 40 to retract into the housing 32.

In another embodiment, a retainer 51 formed at the bottom of the button 38 "can be used to secure the abrasive surface inside the housing after having achieved the desired amount of abrasion. This embodiment is illustrated schematically with Figures 9 and 10. A coupler is used to adapt a microabrasive device with a handle to the 38 "button. Any type of coupler that can connect the handle of a microabrasive device with a button that can be rotated inside a housing is provided. The coupler could adapt a microabrasive device, for example, as shown in Figures 1-2 with the button 38 ". The size of the retainer 51 compared to the opening 36 'is designed to ensure that a technician or user applying the device Microabrasive apply sufficient force to the button 38 ", while the retainer 51 is forced through the opening 36 '. That is, a predetermined amount of force will be necessary to force the button towards the subject's skin. In one embodiment, button 38 "can be activated by this predetermined force and then rotated mechanically (using a torsion spring, for example) by causing the abrasive surface 5 'of a microabrasive device to be turned while applied against the subject. The force of the torsion spring that causes rotation would result in the appropriate amount of abrasion to the subject's skin. fifty

In another embodiment, after pressing the push button 38 "through the hole 36 ', the manual rotation of the button 38" would cause the abrasive surface 5' to rotate. A light spring 46 'around the bar attached to the button 38' and placed inside the housing 32 'would be compressed when the button 38 "is pressed so that after the release of the button 38", the abrasive surface would rotate in the opposite direction, as described above. However, the retainer 51 stops at the top 34 'and the technician or user will have to pull the retainer 51 through the opening 55 36'. This is a safety feature according to the invention, since the abrasive surface of the rotary delivery device retracts into the housing 32 ’and remains intact for safe disposal.

The applicants determined through experiments that in order for the microabrasive device to produce repeatable results and administer the appropriate dose of substance or medication within the epidermal layer of a patient,

it is necessary to sufficiently control the amount of pressure applied to the microabrasive device. According to the invention, the microabrasive matrix surface 5 should only optimally alter the cornea layer. If a lot of pressure is applied, the microabrasive device can remove too much of the epidermal layers. On the other hand, if not enough pressure is applied, the microabrasive surface may not penetrate the corneal layer. This minor abrasion may result in the substance or medication administered to the body not being sufficient. The control of the applied pressure helps determine the depth of penetration, as well as the amount of force to achieve the desired penetration and the desired abrasion. The methods and devices to control the abrasion process are described in their entirety in the US application in process of the applicant Ref # P-5370.

In yet another embodiment of the present invention a rotating abrasive device is shown in the cross-sectional view of Figure 11. For operation the user removes the cover (not shown), which protects an adhesive surface 66 and joins the port of fluid 67 during storage. The device 60 is pressed against the skin, which compresses the spring 63 and applies a predetermined pressure to the abrasive surface 68. The adhesive 66, preferably medical level, holds the device 60 against the skin more strongly than the pressure exerted by the spring 63. Then the piston 69, which injects a liquid substance, for example, a vaccine, drug, diluent, etc., is pressed into the fluid reservoir 70 formed by the closure of the adhesive 66 around the abrasive surface 68. 15 The abrasive surface 68 has fluid channels 71 between the microabrasive surfaces 68, and is essentially immersed in the medication bath during use. The user then rotates the rear cylinder head 72 in a clockwise direction until it can no longer be rotated. The number of turns is predetermined by the number of threads 65 and 64 between the rear cylinder head 61 and the base 62 respectively. The device 60 is then removed from the skin and removed.

To ensure a more even abrasion of the corneal layer the abrasive surfaces 68 have an inverse taper, 20 which provides an equal scanning area at each radius. Figures 12 and 13. Several designs and configurations of microprotrusions that are fully described in the US application in process of the P-5369B applicant, can be attached to or are an integral part of the abrasive surface 58.

Preferably the abrasive assembly 72, Figure 13, can be adjusted by pressure on the base 62, Figures 12, 14 and 15, and preferably extends from about 0.1 mm to about 4 mm beyond the abrasive surface 66 25 before use. It will preferably rotate freely within the base 62 through the opening 83 in the base 62. The rear grooves 80 in the abrasive assembly 82 are coupled with the elements receiving grooves 81 in the rear cylinder head 61, which is used to rotate the scraper. The rear cylinder head 61 will then move down along the rear grooves 80 as it is rotated on the base threads 65. It is anticipated that a feature that would prevent the rear cylinder head 61 from inadvertently rotating counterclockwise out of the base 62 could be integrated or added to the design of the microabrasive 60.

It is also envisaged, and within the scope of the invention, that several other designs can be adapted to activate or enable the rotating action of the device. Some of these examples could be a through hole to allow the rear cylinder head 61 to rotate as a rotary telephone dial, a drive key or pair of "spikes" or flanges that can be provided to allow the rear cylinder head to rotate. 35

A piston 69 or other fluid dispensing components may be provided with the microabrasive mounted 60. Several fluid-containing elements are provided to retain, store and retain the substance to be administered or a diluent, if the abrasive surfaces 68 are coated with a substance dry For example, a glass or polymer container or a standard insulin cartridge or a vial or a flexible container can be used. Any reservoir containing fluids known in the art can be used. 40

Applicants also provide for an electronic rotating management device. In said device, a piezoelectric chip is used to rotate the surface of microabrasive matrix. Said device could preferably have a spring to determine the amount of downward force applied against the skin of a subject in addition to the electronic components necessary to rotate the surface of microabrasive matrix. In addition, the spring can control the speed of rotation of the abrasive surface and the value of the spring is configured to optimally effect abrasion of the skin.

The preferred method and the rotating device can be placed against the skin of a subject and then a button can be pressed to force the microabrasive matrix device against the skin in a circular fashion, while a housing of the device remains fixed on the subject's skin. As described above, rotation can be achieved manually, mechanically or electronically and the downward force applied can be controlled by prestressed spring, by technician 50 or electronically via a pressure transducer.

In a preferred method for abrasion of the skin using circular motion, the microabrasive device 2 can be rotated through the skin of a patient at least two approximately complete rotations. That is, the first approximately complete rotation could be clockwise, while the second approximately complete rotation is counterclockwise or vice versa. The patient's skin can be scraped in opposite rotating directions. In other embodiments, the microabrasive device can be rotated approximately 180 ° against the skin in any direction. The structural design of the microarray of the microabrasive device according to the invention allows the medicament or substance to be absorbed more efficiently thus allowing less medication or substance to be applied to a patient's skin or abrasive coating surface 5.

Depending on the substance or medication applied using the microabrasive device, different arrays of microprotrusions that form the abrasive surface may perform better. It will be understood that the foregoing description of the present invention is susceptible to various modifications, changes and adaptations, and these are also intended to be within the meaning and range of equivalents of the appended claims.

5

Claims (8)

1. A rotating abrasive device (10) comprising: a housing (32) comprising at least one housing element, wherein said at least one housing element is selected from the group consisting of an upper housing, a lower housing, an internal housing, an external housing, and combinations thereof . 5 at least one housing element adapted to rotate; at least one matrix of microprotrusions (14) adapted to alter the skin of a subject when it is rotated; a mechanical rotating means for mechanically rotating said at least one microprotrusion matrix (14) against the skin of a subject with sufficient force to substantially alter and penetrate the cornea layer of the subject without perforating said cornea layer. 10 2. The rotating abrasive device (10) of claim 1, further comprising a substance delivery port adapted to apply a substance to the skin of said subject at an administration site before or simultaneously with the mechanical rotation of said matrix on said administration site. 3. The rotating abrasive device (10) of claim 2, wherein the housing (32) further comprises at least one fixed element. fifteen 4. The rotating abrasive device of claim 3, wherein the at least one element adapted to rotate is further adapted for manual rotation. 5. The rotating abrasive device (10) of claim 1, further comprising: an interlocking mechanism placed inside said abrasive housing (32) to hold said fixed microabrasive matrix until it is deactivated. twenty 6. The rotating device according to claim 5, wherein said interlocking mechanism comprises: a button (38) protruding through the abrasive housing (32), said button (38) is coupled with a longitudinally movable bar; Y a spring (46) within said abrasive housing (32) and around said longitudinally movable bar, wherein said microabrasive matrix is coupled with one end of said longitudinally movable bar so that said spring (46) holds said fixed microabrasive matrix until said button (38) is pressed thereby deactivating said interlocking mechanism. 7. The rotating device according to claim 6, further comprising a freely rotating sleeve mounted within said abrasive housing (32), said sleeve has an end face with which the microabrasive matrix joins and has threads with which the end of said longitudinally movable bar is connected so that a force applied to said button (38) causes said longitudinally movable bar to move along the threads of said sleeve thus rotating said microabrasive matrix. 8. The rotating device according to claim 5, further comprising means for retracting said microabrasive matrix within said abrasive housing (32). 35