EP1898807A1 - Microprojections dotees d'elements de commande capillaire et procede correspondant - Google Patents

Microprojections dotees d'elements de commande capillaire et procede correspondant

Info

Publication number
EP1898807A1
EP1898807A1 EP06739975A EP06739975A EP1898807A1 EP 1898807 A1 EP1898807 A1 EP 1898807A1 EP 06739975 A EP06739975 A EP 06739975A EP 06739975 A EP06739975 A EP 06739975A EP 1898807 A1 EP1898807 A1 EP 1898807A1
Authority
EP
European Patent Office
Prior art keywords
microprojection
control feature
capillary control
approximately
width
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP06739975A
Other languages
German (de)
English (en)
Inventor
Joseph C. Trautman
Richard Wilhem Jansen Van Rens
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alza Corp
Original Assignee
Alza Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alza Corp filed Critical Alza Corp
Publication of EP1898807A1 publication Critical patent/EP1898807A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/20—Surgical instruments, devices or methods, e.g. tourniquets for vaccinating or cleaning the skin previous to the vaccination
    • A61B17/205—Vaccinating by means of needles or other puncturing devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053—Methods for producing microneedles

Definitions

  • the present invention relates to devices and methods for delivering a biologically active agent transdermally using a coated microprojection array. More particularly, the invention relates to devices and methods for reducing the variability in the amount of active agent coated on the microprojections, thus improving the consistency of delivered amount.
  • Active agents are most conventionally administered either orally or by injection. Unfortunately, many active agents are completely ineffective or have radically reduced efficacy when orally administered, since they either are not absorbed or are adversely affected before entering the bloodstream and thus do not possess the desired activity. On the other hand, the direct injection of the agent into the bloodstream, while assuring no modification of the agent during administration, is a difficult, inconvenient, painful and uncomfortable procedure which sometimes results in poor patient compliance.
  • transdermal delivery provides for a method of administering biologically active agents that would otherwise need to be delivered via hypodermic injection, intravenous infusion or orally.
  • Transdermal delivery when compared to oral delivery avoids the harsh environment of the digestive tract, bypasses gastrointestinal drug metabolism, reduces first-pass effects, and avoids the possible deactivation by digestive and liver enzymes.
  • transdermal is used that is used to refer to delivery of an active agent (e.g., a nucleic acid or other therapeutic agent such as a drug) through the skin to the local tissue or systemic circulatory system without substantial cutting or piercing of the skin, such as cutting with a surgical knife or piercing the skin with a hypodermic needle.
  • an active agent e.g., a nucleic acid or other therapeutic agent such as a drug
  • Transdermal agent delivery includes delivery via passive diffusion as well as by external energy sources, including electricity (e.g., iontophoresis) and ultrasound (e.g., phonophoresis). While most agents will diffuse across both the stratum corneum and the epidermis, the rate of diffusion through the stratum corneum is often the limiting step. Many compounds, in order to achieve a therapeutic dose, require higher delivery rates than can be achieved by simple passive transdermal diffusion.
  • a permeation enhancer when applied to a body surface through which the agent is delivered, enhances the flux of the agent therethrough.
  • the efficacy of these methods in enhancing transdermal agent flux has been limited, particularly for larger molecules.
  • the piercing elements disclosed in the noted references generally extend perpendicularly from a thin, flat member, such as a pad or sheet.
  • the piercing elements are typically extremely small, some having dimensions (i.e., a microblade length and width) of only about 25 - 400 ⁇ m and a microblade thickness of only about 5 - 50 ⁇ m.
  • the disclosed systems generally include a reservoir for holding the active agent and a delivery system to transfer the active agent from the reservoir through the stratum corneum, such as by hollow tines or needles.
  • a formulation containing the active agent can be coated on the microprojections.
  • Illustrative are the systems disclosed in U.S. Patent Pub. Nos. 2002/0132054, 2002/0193729, 2002/0177839, 2002/ 0128599, and Application No. 10/045,842, which are fully incorporated by reference herein.
  • Coated microprojection systems eliminate the necessity of a separate physical reservoir and the development of an agent formulation or composition specifically for the reservoir.
  • dip-coating is a method of applying an active agent to the microprojections of a delivery device that generally involves placing the tips of the microprojections in a reservoir of fluid. Capillary action causes the fluid to wick up the sides of the microprojections to variable heights, creating inconsistency in the amount of agent coated and the location of the agent on the microprojection array.
  • the distance the fluid rises up the microprojection is a function the depth the tip is dipped into the fluid, the viscosity of the fluid, the contact angle of the fluid with the microprojection material and the duration the tip is dipped into the fluid. Furthermore, the proximity of the microprojections in the array to each other creates an environment in which the fluid wicks higher in the center of the array than on the perimeter of the array.
  • Another object of the invention is to provide a device and method for more precisely controlling the coating depth on a microprojection.
  • one aspect of the invention comprises a transdermal delivery device comprising a microprojection member having at least one stratum corneum- piercing microprojection with a capillary control feature, wherein the microprojection has a length running from a distal tip to a proximal end and a thickness, wherein the capillary control feature is located between the distal tip and the proximal end, and wherein the microprojection has a first width at the capillary control feature location.
  • the capillary control feature is located in the range of approximately 25 ⁇ m to 200 ⁇ m from the distal tip of the microprojection.
  • the capillary control feature comprises a scribe line running perpendicular to the microprojection length.
  • the scribe line extends at least 50% of the first width on each side of the microprojection.
  • the scribe line can be configured as a ridge or a trough.
  • the scribe line has a thickness in the range of approximately 5 ⁇ m and 25% of the thickness of the microprojection.
  • the capillary control feature comprises a void.
  • the void has a horizontal dimension up to approximately half the width of the microprojection at the location of the capillary control feature.
  • the capillary control feature comprises a transition from a maximum width to a minimum width at the capillary control feature location.
  • the microprojection has a minimum width in the range of approximately 25% to 100% of the maximum width, and more preferably, in the range of approximately 35% to 70% of the maximum width. Even more preferably, the minimum width is approximately 50% of the maximum width.
  • the microprojection has a minimum width that is in the range of approximately 10 ⁇ m to 120 ⁇ m less than said maximum width.
  • the capillary control feature comprises a hydrophobic coating.
  • Hydrophobic coatings are selected from the group consisting of polytetrafmoroethylene, parylene and silicon.
  • the delivery devices of the invention further comprise a coating of a biologically active agent applied to the microprojection from the distal tip to the capillary control feature.
  • the coating is applied to the microprojection with a static contact angle greater than 20 degrees, and more preferably, between 30 and 60 degrees.
  • the coating comprises a formulation having a biologically active agent selected from the group consisting of growth hormone release hormone (GHRH), growth hormone release factor (GHRP), insulin, insultropin, calcitonin, octreotide, endorphin, TRN, NT-36 (chemical name: N-[[(s)-4-oxo-2- azetidinyl] carbonyl]-L-histidyl-L-prolinamide), liprecin, pituitary hormones (e.g., HGH, HMG, desmopressin acetate, etc), follicle luteoids, aANF, growth factors such as growth factor releasing factor (GFRF), bMSH, GH, somatostatin, bradykinin, somatotropin, platelet-derived growth factor releasing factor, asparaginase, bleomycin sulfate, chymopapain, cholecystokinin
  • GHRH growth hormone release hormone
  • the biologically active agent comprises an immunologically active agent selected from the group consisting of proteins, polysaccharide conjugates, oligosaccharides, lipoproteins, subunit vaccines, Bordetella pertussis (recombinant PT accince - acellular), Clostridium tetani (purified, recombinant), Corynebacterium diphtheriae (purified, recombinant), Cytomegalovirus (glycoprotein subunit), Group A streptococcus (glycoprotein subunit, glycoconjugate Group A polysaccharide with tetanus toxoid, M protein/peptides linked to toxing subunit carriers, M protein, multivalent type-specific epitopes, cysteine protease, C5a peptidase), Hepatitis B virus (recombinant Pre Sl, Pre-S2, S, recombinant core protein), Hepatitis B virus (recombinant Pre Sl
  • the invention also comprises methods of applying a coating of a biologically active agent to a transdermal delivery device, generally including the steps of providing a microprojection member having at least one stratum corneum-piercing microprojection with a capillary control feature, wherein the microprojection has a length running from a distal tip to a proximal end, a thickness, wherein the capillary control feature is located between the distal tip and the proximal end, and wherein the microprojection has a first width at the capillary control feature location; applying a formulation of the biologically active agent to a location proximal the distal tip of the microprojection so that the formulation migrates to the capillary control feature; and drying the formulation to form a coating.
  • the step of applying the formulation comprises dip coating.
  • FIGURE 1 is a perspective view of a microprojection member having a coating deposited on the microprojections, according to the invention
  • FIGURE 2 is a detail view of an embodiment of a microprojection having a scribed capillary control feature, according to the invention
  • FIGURE 3 is a detail view of an alternate embodiment of a microprojection having a capillary control feature comprising a void, according to the invention
  • FIGURE 4 is a detail view of another embodiment of a microprojection having a capillary control feature comprising a reduced width configuration, according to the invention.
  • FIGURE 5 is a detail view of yet another embodiment of a microprojection having a capillary control feature comprising a hydrophobic coating, according to the invention.
  • FIGURES 6 and 7 are graphical illustrations comparing capillary rise heights for microprojections having features of the invention to prior art microprojections.
  • FIGURES 8 and 9 are graphical illustrations comparing meniscus volumes for microprojections having features of the invention to prior art microprojections.
  • transdermal means the delivery of an agent into and/or through the skin for local or systemic therapy.
  • biologically active agent refers to a composition of matter or mixture containing an active agent or drug, which is pharmacologically effective when administered in a therapeutically effective amount.
  • microprojection array As used herein, the term "microprojection array,” “microprojection member,” and the like, all refer to a device for delivering an active agent into or through the skin that comprises a plurality of microprojections on which the active agent can be coated.
  • microprojections refers to piercing elements that are adapted to pierce or cut through the stratum corneum into the underlying epidermis layer, or epidermis and dermis layers, of the skin of a living animal, particularly a human.
  • the microprojections have a blade length of less than 1000 ⁇ m, and preferably less than 500 ⁇ m. In one embodiment, the microprojections have a length in the range of 50 - 145 ⁇ m. The microprojections typically have a width in the range of about 75 - 500 ⁇ m and a thickness in the range of about 5 — 50 ⁇ m.
  • the microprojections can be formed in different shapes, for example by etching or punching a plurality of microprojections from a thin sheet and folding or bending the microprojections out of the plane of the sheet to form a configuration, such as that shown in Fig. 1.
  • the microprojection member can also be formed in other known manners, such as by forming one or more strips having microprojections along an edge of each of the strip(s).
  • Exemplary methods of forming metal microprojection are disclosed in Trautman et al., U.S. Patent No. 6,083,196; Zuck, U.S. Patent No. 6,050,988; and Daddona et al, U.S. Patent No. 6,091,975; the disclosures of which are incorporated by reference herein in their entirety.
  • microprojection members that can be used with the present invention are formed by etching silicon using silicon chip etching techniques or by molding plastic using etched micro-molds. Silicon and plastic microprojection members are disclosed in Godshall et al., U.S. Patent No. 5,879,326; the disclosure of which is incorporated by reference herein.
  • the terms “deliver,” “delivering,” and all variations thereof, refer to and include any means by which an active agent can be administered into or through the skin.
  • the term "thickness,” as it relates to coatings, refers to the average thickness of a coating as measured over substantially all of the portion of a substrate that is covered with the coating.
  • a stratum corneum- piercing microprojection member 10 for use with the present invention.
  • the member 10 includes a plurality of microprojections 12 having a coating 14 disposed thereon.
  • Coating 14 comprises a dried formulation having one or more biologically active agents.
  • the microprojections 12 extend at substantially a 90° angle from a substrate, such as sheet 16, having openings 18.
  • the microprojections 12 are preferably formed by etching or punching a plurality of microprojections 12 from a thin metal sheet 16 and bending the microprojections 12 out of a plane of the sheet.
  • Metals such as stainless steel, titanium and nickel titanium alloys are preferred.
  • the coating 14 preferably covers the microprojection 12 from a capillary control feature 20 to the distal tip 22.
  • the coating 14 can be formed upon the microprojections 12 by a variety of known methods.
  • a liquid formulation is applied to microprojection 12 and then dried to form coating 14.
  • capillary control feature 20 is positioned within the nominal rise height of the coating formulation at a location selected to result in a desired coating depth.
  • the applied fluid formulation wicks along the microprojection 12 until capillary control feature 20 restricts the migration.
  • a presently preferred means of applying a formulation to the microprojections of the invention means is dip-coating. This method generally involves immersing microprojections 12 into a coating formulation. Depending upon the properties of the coating formulation and the desired loading amount, the microprojections can be lowered into the formulation to any depth up to the capillary control feature 20. In some embodiments, it may be desirable to dip only a distal portion of the microprojection tip into the formulation.
  • the capillary control features of the invention are applicable to other means of applying coatings, so long as the applied formulation is fluid or otherwise susceptible to migration. As will be appreciated by one having ordinary skill in the art, the use of the capillary control features of the invention minimizes such migration and restricts the coating depth.
  • roller coating which employs a roller coating mechanism that similarly limits the coating 14 to the tips of the microprojections 12.
  • the roller coating method is disclosed in U.S. Application No. 10/099,604 (Pub. No. 2002/0132054), which is incorporated by reference herein in its entirety.
  • the disclosed roller coating method provides a smooth coating that is not easily dislodged from the microprojections 12 during skin piercing.
  • a further coating method that can be employed within the scope of the present invention comprises spray coating.
  • spray coating can encompass formation of an aerosol suspension of the coating composition.
  • an aerosol suspension having a droplet size of about 10 to 200 picoliters is sprayed onto the microprojections 10 and then dried.
  • Pattern coating can also be employed to coat the microprojections 12.
  • the pattern coating can be applied using a dispensing system for positioning the deposited liquid onto the microprojection surface.
  • the quantity of the deposited liquid is preferably in the range of 0.1 to 20 nl/microprojection. Examples of suitable precision-metered liquid dispensers are disclosed in U.S. Patent Nos. 5,916,524; 5,743,960; 5,741,554; and 5,738,728; which are fully incorporated by reference herein.
  • Microprojection coating formulations or solutions can also be applied using ink jet technology using known solenoid valve dispensers, optional fluid motive means and positioning means which is generally controlled by use of an electric field.
  • Other liquid dispensing technology from the printing industry or similar liquid dispensing technology known in the art can be used for applying the pattern coating of this invention.
  • the invention is directed to microprojection designs and methods having reduced coating variability.
  • the microprojection has a capillary control feature, located so that capillary action is disrupted or minimized at the desired coating depth.
  • the invention includes a microprojection 30 having a capillary control feature comprising a scribe line 32.
  • a scribe line 32 generally is a trough or ridge that runs substantially perpendicular to the length of the microprojection.
  • scribe line 32 runs continuously from edge to edge on both sides of the microprojection.
  • scribe line 32 can run intermittently across at least half the distance.
  • the thickness of scribe line 32 refers to depth of the trough or height of the ridge, and is measured as the differential from the plane of the microprojection.
  • the thickness of scribe line 32 is approximately equal to its width. More preferably, the thickness is in the range of approximately 5 ⁇ m and 25% of the thickness of the microprojection.
  • Scribe line 32 is located the distance from the tip 34 of the microprojection that the fluid is intended to coat.
  • scribe line 32 is located in the range of approximately 25 ⁇ m to 200 ⁇ m from the distal tip 34 of the microprojection 30.
  • microprojection 40 has a capillary control feature comprising at least one void 42.
  • the width of the microprojection on each side of void 42 is preferably in the range of approximately 25 ⁇ m and half the width of the microprojection.
  • void 42 is located so that the distal portion of the void (that closest to the tip of the microprojection) corresponds to the desired coating depth.
  • the distal portion of void 42 is preferably located in the range of approximately 25 ⁇ m to 200 ⁇ m from the tip 44 of microprojection 40.
  • the microprojection is configured to minimize the effect of capillary action to wick fluid beyond a desired region.
  • microprojection 50 has a width that increases from distal tip 52 to location 54 of maximum width. The width of microprojection 50 then decreases to location 56 of minimum width.
  • the capillary control feature is the reduction of width at location 56. Preferably, location 56 corresponds to the desired coating depth. As shown in Fig. 4, coating 58 wicking action causes migration only in the minimum width 56 location. Microprojection 50 still presents adequate surface area below minimum width 56 to allow a desired amount of coating. As one having skill in the art can appreciate, decreasing the width of the microprojection reduces variability in coating height but must be balanced against the need to retain sufficient structural integrity.
  • the maximum width at location 54 is in the range of approximately 10 ⁇ m to 120 ⁇ m wider than the minimum width at location 56.
  • the minimum width at location 56 of the microprojection is preferably in the range of approximately 25% to 100%, and more preferably, in the range of approximately 35% to 70%, of the maximum width at location 54.
  • the minimum width at location 56 is approximately 50% of the maximum width at location 54.
  • the reduction to minimum width is located at the desired coating depth, such as in the range of approximately 25 ⁇ m to 200 ⁇ m from the distal tip of the microprojection.
  • the capillary control feature comprises a hydrophobic coating.
  • microprojection 60 has a hydrophobic coating 62 located at the proximal boundary of the location 64 corresponding to the desired coating depth.
  • the hydrophobic coating is located in the range of approximately 25 ⁇ m to 200 ⁇ m from the distal tip 66 of the microprojection.
  • the hydrophobic coating is selected from the group consisting of polytetrafluoroethylene, parylene and silicon.
  • Presently preferred characteristics of the microprojection members of the invention include a microprojection density in the range of approximately 10 to 2000 per cm 2 , a microprojection length in the range of approximately 50 to 500 ⁇ m, a microprojection maximum width in the range of approximately 20 to 300 ⁇ m, and a microprojection thickness in the range of approximately 10 to 50 ⁇ m.
  • the capillary control features of the invention minimize variations in coating depth as compared to prior art microprojection designs as demonstrated by the graphical illustrations shown in Figs. 6 and 7. These graphs show the capillary rise measured for five tip microprojection members, each having the same boundary conditions and tip configurations, with Fig. 6 showing prior art designs and Fig. 7 showing microprojections having capillary control features.
  • the rise heights show a significant amount of variation, 15 ⁇ m or more.
  • the graph also shows that neighboring microprojections affect capillary rise heights, leading to different loading amounts in different positions of the microprojection array.
  • FIG. 7 shows that microprojections having capillary control features offer consistent capillary rise heights and exhibit minimal variability. Also, the position of the microprojection within the array does not have a significant effect on coating depth for designs incorporating capillary control features.
  • Figs. 8 and 9 are graphical illustrations that compare the meniscus volume for a conventional microprojection tip with a microprojection tip having capillary control features, respectively, when dipped to a depth of 400 ⁇ m.
  • the fluid loading on the tip shown in Fig. 8 is calculated to be 6.3 x 10 "12 m 3 as compared to the 36.2 x 10 "12 m 3 for the capillary controlled microprojection of Fig. 9. Accordingly, the use of capillary control features can result in approximately a six-fold increase in loading.
  • the contact angle of the meniscus limits the volume of coating on the microprojection.
  • Microprojections formed from titanium for example, exhibit a contact angle of approximately 65° as shown in Fig. 8, and microprojections formed from stainless steel have an even lower contact angle.
  • the use of a capillary control feature allows the contact angle to approach 90°, effectively removing contact angle as a limiting factor.
  • the contact angle with a microprojection having a capillary control feature is approximately 88°. Accordingly, the use of capillary control features allows coatings to be applied to the microprojection at contact angles greater than would be possible without such features.
  • the coating formulation can be applied with a contact angle greater than approximately 25 degrees. More preferably, the coating formulation can be applied with a contact angle between approximately 30 and 60 degrees.
  • the biologically active agent comprises a therapeutic agent in all the major therapeutic areas including, but not limited to, anti- infectives, such as antibiotics and antiviral agents; analgesics, including buprenorphine and analgesic combinations; anesthetics; anorexics; antiarthritics; antiasthmatic agents, such as terbutaline; anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals; antihistamines; anti-inflammatory agents; antimigraine preparations; antimotion sickness preparations, such as scopolamine and ondansetron; antinauseants; antineoplastics ; antiparkinsonism drugs; antipruritics; antipsychotics; antipyretics; antispasmodics, including gastrointestinal and urinary; anticholinergics; sympathomimetrics; xanthine derivatives; cardiovascular preparations, including calcium channel blockers such as nifedipine;
  • the biologically active agent is selected from the group consisting of growth hormone release hormone (GHRH), growth hormone release factor (GHRF), insulin, insultropin, calcitonin, octreotide, endorphin, TRN, NT-36 (chemical name: N-[[(s)-4-oxo-2-azetidinyl] carbonyl]-L-histidyl-L-prolinamide), liprecin, pituitary hormones (e.g., HGH, HMG, desmopressin acetate, etc), follicle luteoids, aANF, growth factors such as growth factor releasing factor (GFRF), bMSH, GH, somatostatin, bradykinin, somatotropin, platelet-derived growth factor releasing factor, asparaginase, bleomycin sulfate, chymopapain, cholecystokinin, chorionic gonadotropin
  • GHRH growth hormone release hormone
  • Suitable biologically active agents comprise immunologically active agents, such as vaccines and antigens in the form of proteins, polysaccharide conjugates, oligosaccharides, and lipoproteins.
  • Specific subunit vaccines in include, without limitation, Bordetella pertussis (recombinant PT accince - acellular), Clostridium tetani (purified, recombinant), Corynebacteriurn diphtheriae (purified, recombinant), Cytomegalovirus (glycoprotein subunit), Group A streptococcus (glycoprotein subunit, glycoconjugate Group A polysaccharide with tetanus toxoid, M protein/peptides linked to toxing subunit carriers, M protein, multivalent type-specific epitopes, cysteine protease, C5a peptidase), Hepatitis B virus (recombinant Pre Sl, Pre-S2, S, recombin
  • Suitable immunologically active agents also include nucleic acids, such as single- stranded and double-stranded nucleic acids, supercoiled plasmid DNA, linear plasmid DNA, cosmids, bacterial artificial chromosomes (BACs) 5 yeast artificial chromosomes (YACs), mammalian artificial chromosomes, and RNA molecules.
  • nucleic acids such as single- stranded and double-stranded nucleic acids, supercoiled plasmid DNA, linear plasmid DNA, cosmids, bacterial artificial chromosomes (BACs) 5 yeast artificial chromosomes (YACs), mammalian artificial chromosomes, and RNA molecules.
  • the microprojection member 10 is preferably suspended in a retainer ring by adhesive tabs, as described in detail in Co-Pending U.S. Application No. 09/976,762 (Pub. No. 2002/0091357), which is incorporated by reference herein in its entirety.
  • the microprojection member 10 is applied to the patient's skin.
  • the microprojection member 10 is applied to the skin using an impact applicator, such as disclosed in Co-Pending U.S. Application No. 09/976,798, which is incorporated by reference herein in its entirety.
  • the present invention provides an effective and efficient means for enhancing the transdermal flux of a biologically active agent into and through the stratum corneum of a patient.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Surgery (AREA)
  • Medical Informatics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Anesthesiology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne des procédés et dispositifs permettant de réduire la variabilité de revêtement d'un dispositif de microprojections destiné à la délivrance transdermique. Ce dispositif comprend au moins une strate de microprojections de perçage de la couche cornée. Chaque microprojection a un élément de commande capillaire qui limite la migration de la formulation de revêtement.
EP06739975A 2005-03-28 2006-03-27 Microprojections dotees d'elements de commande capillaire et procede correspondant Withdrawn EP1898807A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US66628905P 2005-03-28 2005-03-28
PCT/US2006/011530 WO2006105233A1 (fr) 2005-03-28 2006-03-27 Microprojections dotees d'elements de commande capillaire et procede correspondant

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EP1898807A1 true EP1898807A1 (fr) 2008-03-19

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EP (1) EP1898807A1 (fr)
JP (1) JP2008534151A (fr)
CN (1) CN100591293C (fr)
AU (1) AU2006230308A1 (fr)
CA (1) CA2602814A1 (fr)
WO (1) WO2006105233A1 (fr)

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JP2008534151A (ja) 2008-08-28
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AU2006230308A1 (en) 2006-10-05
CA2602814A1 (fr) 2006-10-05
WO2006105233A1 (fr) 2006-10-05

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