US2893392A - Article of manufacture for intracutaneous injections - Google Patents

Article of manufacture for intracutaneous injections Download PDF

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US2893392A
US2893392A US707703A US70770358A US2893392A US 2893392 A US2893392 A US 2893392A US 707703 A US707703 A US 707703A US 70770358 A US70770358 A US 70770358A US 2893392 A US2893392 A US 2893392A
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injection
unit
article
skin
manufacture
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US707703A
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Wagner Alan Richard
Cooper Murray Sam
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Wyeth Holdings LLC
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Wyeth Holdings LLC
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/20Surgical instruments, devices or methods, e.g. tourniquets for vaccinating or cleaning the skin previous to the vaccination
    • A61B17/205Vaccinating by means of needles or other puncturing devices

Description

y 1959 A. R: WAGNER ETAL 2,893,392-

ARTICLE; OF MANUFACTURE FOR INTRACUTANEIOUS INJECTIONS Filed Jan. 8, 1958 FIG.9 FIG. IO

8 INVENTOR. ALAN RICHARD WAGNER BY MURRAY SAM COCPER ATTORNEY United States Patent ARTlCLEDFMANUFACTURE FORINTRA- 'CUTANEOUS INJECTIONS Richard -Wagner, Park *Ridge, and Murray Sam -.-.Cooper, Dumont N.J. assiguors; to American Cyan- .ainid Company, New York, N.Y., a corporation of 7 Metric -Application January 8, :-1958, SeriaI No. 707,703 51Cl2'1inis. (Cl; 128-153) This "invention relates'to an article ofmanufacture "-suit'able 'for useas a means -of:administering' intracutaneousinje'ctions, a more particularly; to 21* unit consisting of a sealed container which encloses both a'biolog'ically "active *fluid' and a device capable of puncturing this container and administering a single-puncture or a multiple- *pim'eture intracutaneous injection. In a preferred em- -lfxidirrient, it consists of'a disposable sealed plastic conner'--which"encloses both a biologically active'fiuid c pable-ofeli'citing an-allergic reaction or producing a vaceinirermuocai infection and a plate or 'disk, which *dislc-"or"plate is perforated in such manner that one or a nmiiber-"of sharp-pointsare formed which-are capable be-puncturin the plastic container and also penetrating iilt: the skin" beneath the plastic container thereby adnist in'g asingle-puncture or multiple-puncture intracutaneous injection.

intracutaneousinjections are employed inmedical prac- -ti ef6ra wide= variety ofpurposes. They are used-to vaci mate againsta number of diseases such' as smallpox and "ti lbetculosis. They are used-diagnostically to'dete'ct allergies of various kinds and sensitivity toa wide-variety of biological products such as penicillin, horse -serum,-and "variousroorganisms {such as those causing tuberculosis'. I racutaneousinjections are also used'asmeans or: desensitizing aninialsagainst-a wide-variety ofallergens. Various techniqueshave been developed for the application or these vaccinating and diagnostic agents and allergens,-but each of *these has certain disadvantages.

-Direct skin su'rface contact tests are 'painless and re- -=quire little skillin applicationfbut are unreliable and "u -some areas of "the world extremely difiicult to use. or e'xample, adhesivepla's'ter frequently does not hold -to:pe1 'spiringskin-areas and -may irritate the skin, thus eliciting false pos'it-ive reactions, as some skin surface areas are more "s'ensitive than others. Thus, test results -may'be erratic.

Abrasion or scratch tests are relatively painless, but =-'they necessitate expert tech'nique andhave proved unreliable in many instanc'es and places. For example, it is difiicult to 'applyan abrasive contained in grease to a per'spirin'g skin, "scratches may vary in depth, glass containers' of test fluid may become contaminated, and the like.

-Intracutaneousinjection methods are used throughout *rthe-worldwhere accurate and reproducible information -is desired. Most of these testsare' performed at present bysinjection directlydnto the skin by means of singleor multiple-dose syringes, carpules, "syrettes-and the like, or alternatively, by some adaptation of a device which admini's'tei's -multiple skin punctures by means of a vertical stabbing through a'drop of test material placed on the surface; of the skin. Difliculties have been encounf'tered'inperfofming ihtr'acutaneous injections by present l techniques. L Singleand inultiple dose syringes-are'relativ'ely' expensive;have a tendency to leak, and are easily broken. Separate syringes and needles are preferred for each test to avoid transmittal of bloodborne diseases and contamination.

-2 (homologous 'serum hepa'titis, etc.) L fronr one person to another. False tests have resulted from contamination by traces of allergen that remain in the syringes-even after thorough washing and boiling-especially in cases where a'weaker allergen has been used subsequent to a strong allergen; Contamination of bottles of testmaterial-may culties are frequently encountered. 'Carpules' are also relatively expensive and'the 'glass cartridgesare-subje'ct to breakage. Separate needles-"should'beusedto -avoid 'transmi'ttal of bloodborne diseases fromone'personto "another.

Syrettes are' dispos able"and dosolve thefproblem er "expense, breakagepa'n'd contamination. Howevenanother problem common -to-syringes, carpules, aud s grade assistantsextremely difiicult.

*Some multiple-puncture devices are relatively expensive, not easily obtainable, and have energized moving parts which are subject to break-down-and which have a noise-plus-shock type of action that 'may render-children and nativepopulations uncooperative.

Other multiple puncture devices, such-as pronged steel disks,--with or without holders, usuallynecessitate the use of glass vials or glass capillary tubes as containers" for test materials and therefore'introduce the dangers of breakage Distancefrom a source "of supply might result in the presence of disks Without test material or testmaterial without disks.

"An object of this invention is -to:provide a single-puncture or multiple-puncture type,--'self-contained skin-test "unit which-is disposable, inexpensive, unbreakable, sterilizable, capable ofbeing'standardized and capableof practically painless, easy, fool-proof operation in the hands of-unskilled personnel. The last mentionedis an especially important featureof the-invention; that is, it is simply and easily put to use by p'ersonswithout specialized training. Another important'feature of the invention lies in thefact that it canbe produced in 'a wide range of sizes.

Another important feature ofthe invention is the fact that, as long as the test material is'fluidand does not deteriorate too quickly, any desired: single dose of any test material may be-inc'orporated'in the unit.

In order that the nature of 'the'invention may be more apparent, reference is made to the single sheet of drawunit of Figure 3 taken along line 5,-5.

Figure 6 is a perspective view of the unit ofFigure 3. Figure 7 is a perspective view of a somewhat modi- "fied injection device.

Figure 8 is also a perspective view of another form of injection device.

Figure '9 is a plan view of"stillanother'modification of the injection device.

Figure 10 is across-sectional view taken'along line It), f Figure 9.

Referring again to Figure 1, the injection device of the present invention comprises a plastic envelope 1 containing an injection unit 2 with sharp prongs 3, 4, 5

3 and 6, enclosed within the plastic envelope together with a quantity of a biological liquid 7. The ends and 9 of the plastic envelope are 'sealed, forming a liquid-tight container holding the biological liquid and the injection device.

The biological liquid may be any suitable biological material which is to be used in the intracutaneous injection. When running tests, for instance, to determine whether or not the subject has tuberculosis, the biological liquid would be old tuberculin often referred to as OT whichmay be prepared by evaporating a twelveweek old culture of tubercle bacilli in percent glycerine bouillon down to one-tenth of its original volume, heating to kill the bacteria and filtering to obtain old tuberculin, an amber syrupy fluid which will keep for a longer period of time. A suitable amount of this particular biological liquid to include in each envelope would be about one-half milliliter although smaller or larger volumes may be used. Obviously, different amounts of other biological liquids would be employed as determined by the manufacturer of the unit.

The plastic envelope should be biologically inert, water insoluble and impermeable and, preferably, should be resistant to other organic liquids such as glycerol wthich isoften used in the preparation of vaccines and diagnostic agents. It should be resistant to alcohols. The assembled units as described herein may be stored in ethyl alcohol as a means of keeping the unit aseptic just as surgical sutures are often stored in tubing fluids.

Preferably the envelopeshould be transparent so that those who are using the device may quickly determine where the injection prongs are located, although obviously location of the prongs can be designated in any suitable manner.

Inasmuch as it may be desired to heat-sterilize the unit after assembling and sealing, the plastic envelope should be of a heat-resistant material that is suflicient to withstand sterilizing temperatures. However, when other means of sterilization are employed, heat resistance is not particularly important.

The plastic envelope should also be fairly flexible for ease in handling and applying. The material should be strong enough to withstand packaging operations and handling, yet should be readily pierceable by the injection prongs on the unit within the plastic envelope. Fortunately there are several suitable plastic films available from which the plastic envelope may be made. These includepolyethylene films, films made of polymers of ethylene glycol and terephthalic acid, films of polyvinylidene chloride, vinyl resins, rubber hydrochloride and others sold under such trade'names as Saran, Mylar, Genitron, Pliofilm, and Cryovac. Suitable films range from about 0.0005 inch and thicker, the practical limit being dependent upon the difficulty with which the film may be punctured by the sharp prongs of the injection unit without undue pressure.

The injection unit itself may take a variety of forms some of which are illustrated in Figures 6, 7, 8, and 9. It should be of a non-corrosive material such as stainless steel. There may be only one injection prong as shown in Figure 8 or there may be a multiplicity of prongs. Preferably, but not necessarily, the device should be substantially flat so that pressure may be readily inserted upon it by the thumb or finger. The prongs are preferably about 2 to 3 millimeters in length although they may range from 1 to 5 millimeters depending upon the use to which the instrument is put. A suitable size of the unit as shown in Figure 3 is approximately Y by 7 inch, although obviously larger or smaller units may be used.

The envelope containing the biological liquid of the injection unit may be sealed by any means suitable to the plastic material of which the envelope is made. Heat-sealing is preferred although other means may be employed.

In employing this self-contained, disposable transparent, multiple-puncture, intracutaneous injection pacquet, the terminal quarters of the unit are grasped between the thumb and index finger of each hand and placed against the skin test area in such a way that the sharp points are vertical to the skin surface. The unit is then held in place with one hand and pressure applied by means of the thumb of the other hand is used to drive the points through the wall of the plastic film container and into the skin carrying the test fluid along. Pressure on the plasticfilm tends, of course, to force the liquid within the envelope out and into contact with the skin through which it is carried by the points of the instrument.

This invention may be usefully employed in individual or mass investigations for tuberculin and tetanus sensitivity, diagnosis of histoplasmosis, blastomycosis, coccidimycosis, cryptococcosis, sporotrichosis, allergen sensitivity, smallpox vaccination, and many other purposes wherein intracutaneous injection of a biological is de sired.

Various ways of assembling the article of the present invention will occur to those skilled in the packaging art. A method of assembly suitable to automation is to cut and simultaneously seal short sections from a preformed tube of plastic material, insert the injection disk in the unsealed end, add a desired quantity of the biological liquid, heat-seal the open end of the tube and sterilize the entire unit by heating in a steam autoclave at 5 to 10 pounds pressure for 30 minutes. If the biological liquid is heat-labile, it may be introduced aseptically into the unit after sterilization. Of course, sterilization with ethylene oxide, radiant energy, antiseptics and other means may be employed instead of heat Where practical. Inasmuch as the treatment of these biological liquids will be understood by those skilled in the art, further elaboration appears to be unnecessary.

We claim:

1. An article of manufacture comprising a sealed envelope containing a quantity of biological liquid and an injection device adapted to penetrate the envelope and the epidermis of an animal.

2. An article of manufacture adapted for use in administering intracutaneous injections of a biologically active material comprising a sealed container of pliable film containing a biologically active liquid and an injection device comprising a substantially fiat body having at least one injection prong adapted to penetrate the pliable film and the epidermis of a subject when the unit is placed on the skin and pressure is applied.

3. An article of manufacture in accordance with claim 2 in which the injection prongs are from 1 to 5 millimeters in length.

4. An article of manufacture in accordance with claim 2 in which the injection unit comprises a substantially flat disk of a non-corrosive metal having a plurality of injection prongs of from 1 to 5 millimeters in length.

5. An article of manufacture for intracutaneous injection of old tuberculin which comprises a sealed transparent plastic envelope containing old tuberculin and a substantially flat body having a plurality of sharp prongs of l to 5 millimeters in length adapted to penetrate the envelope and penetrate the skin of a test subject upon application of pressure.

References Cited in the file of this patent UNITED STATES PATENTS 2,619,962 Rosenthal Dec. 2, 1952 2,817,336 Kravitz Dec. 24, l957 2,841,138 Laub July 1, 1958

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Cited By (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3034507A (en) * 1960-05-10 1962-05-15 American Cyanamid Co Intracutaneous injection device
US3072122A (en) * 1959-01-15 1963-01-08 Rosenthal Sol Roy Package for transcutaneous injection
US3074403A (en) * 1960-05-17 1963-01-22 American Cyanamid Co Intracutaneous injector with capillary gap
US3136314A (en) * 1960-08-01 1964-06-09 Kravitz Harvey Vaccinating devices
US3167073A (en) * 1962-01-16 1965-01-26 Rosenthal Sol Roy Transcutaneous injection device
US3221739A (en) * 1962-03-26 1965-12-07 Rosenthal Sol Roy Injection device
US3221740A (en) * 1962-08-31 1965-12-07 Rosenthal Sol Roy Injection device
US3246647A (en) * 1962-07-23 1966-04-19 American Cyanamid Co Disposable intracutaneous injector
US3291129A (en) * 1962-08-10 1966-12-13 Burelle Pierre Laurent Raymond Scarificator for use in vaccination, skin tests, or the like
US3703890A (en) * 1970-08-10 1972-11-28 Milton A Saunders Jr Skin patch test device
US3882999A (en) * 1972-03-09 1975-05-13 Lester R Wellman Opener/re-closer for sealed containers
EP0081975A2 (en) * 1981-12-14 1983-06-22 Nicholas H. Maganias Device and method for allergy testing
US4802493A (en) * 1981-12-14 1989-02-07 Maganias Nicholas H Device and method for allergy testing
US5099857A (en) * 1987-05-29 1992-03-31 Northern Sydney Area Health Service Medical testing device with calibrated indicia
US5104620A (en) * 1990-07-30 1992-04-14 Wiley Fred R Disposable allergy skin testing kit
US6083196A (en) * 1997-12-11 2000-07-04 Alza Corporation Device for enhancing transdermal agent flux
US6219574B1 (en) 1996-06-18 2001-04-17 Alza Corporation Device and method for enchancing transdermal sampling
US6322808B1 (en) 1997-12-11 2001-11-27 Alza Corporation Device for enhancing transdermal agent flux
US6334856B1 (en) 1998-06-10 2002-01-01 Georgia Tech Research Corporation Microneedle devices and methods of manufacture and use thereof
US20020082543A1 (en) * 2000-12-14 2002-06-27 Jung-Hwan Park Microneedle devices and production thereof
US6443307B1 (en) * 2000-01-25 2002-09-03 Michael D. Burridge Medication dispenser with an internal ejector
US20020128599A1 (en) * 2000-10-26 2002-09-12 Cormier Michel J.N. Transdermal drug delivery devices having coated microprotrusions
US20020138049A1 (en) * 1998-06-10 2002-09-26 Allen Mark G. Microneedle devices and methods of manufacture and use thereof
US20030095582A1 (en) * 2000-12-21 2003-05-22 Ackley Donald E. Microneedle array systems
US20030135158A1 (en) * 2001-09-21 2003-07-17 Gonnelli Robert R. Gas pressure actuated microneedle arrays, and systems and methods relating to same
US20030135166A1 (en) * 2001-09-28 2003-07-17 Gonnelli Robert R. Switchable microneedle arrays and systems and methods relating to same
US20030135167A1 (en) * 2001-09-19 2003-07-17 Gonnelli Robert R. Microneedles, microneedle arrays, and systems and methods relating to same
US20030135201A1 (en) * 2001-09-28 2003-07-17 Gonnelli Robert R. Microneedle with membrane
US6611707B1 (en) 1999-06-04 2003-08-26 Georgia Tech Research Corporation Microneedle drug delivery device
US20030181936A1 (en) * 2001-12-20 2003-09-25 Trautman Joseph C. Skin-piercing microprojections having piercing depth control
US20030199810A1 (en) * 2001-11-30 2003-10-23 Trautman Joseph Creagan Methods and apparatuses for forming microprojection arrays
US20040039342A1 (en) * 2000-06-08 2004-02-26 Jonathan Eppstein Transdermal integrated actuator device, methods of making and using same
US20040062813A1 (en) * 2002-06-28 2004-04-01 Cormier Michel J. N. Transdermal drug delivery devices having coated microprotrusions
US20040096455A1 (en) * 2002-08-08 2004-05-20 Yuh-Fun Maa Transdermal vaccine delivery device having coated microprotrusions
US6743211B1 (en) 1999-11-23 2004-06-01 Georgia Tech Research Corporation Devices and methods for enhanced microneedle penetration of biological barriers
US20040236271A1 (en) * 1997-12-10 2004-11-25 Felix Theeuwes Device and method for enhancing transdermal agent flux
US20050031676A1 (en) * 2003-08-04 2005-02-10 Wong Patrick S.L. Method and device for enhancing transdermal agent flux
US20050049625A1 (en) * 2003-08-26 2005-03-03 Steven Shaya Device and method for intradermal cell implantation
US20050106227A1 (en) * 2003-10-28 2005-05-19 Samuel Zalipsky Delivery of polymer conjugates of therapeutic peptides and proteins via coated microprojections
US20050171567A1 (en) * 2004-01-29 2005-08-04 Dehart Damon H. Lancet and method of manufacturing the same
US20050197308A1 (en) * 2000-07-21 2005-09-08 Smithkline Beecham Biologicals S.A. Vaccines
US20050238708A1 (en) * 2004-04-23 2005-10-27 Andrew Jones Sealed capsule including an integrated puncturing mechanism
US20060030811A1 (en) * 2004-08-03 2006-02-09 Wong Patrick S Method and device for enhancing transdermal agent flux
US20060051403A1 (en) * 2004-09-08 2006-03-09 James Matriano Microprojection array with improved skin adhesion and compliance
US20060074377A1 (en) * 2001-04-20 2006-04-06 Cormier Michel J Microprojection array immunization patch and method
US20060195067A1 (en) * 2003-08-25 2006-08-31 Wolter James T Delivery of immune response modifier compounds
US20070161964A1 (en) * 2006-01-10 2007-07-12 Yuzhakov Vadim V Microneedle array, patch, and applicator for transdermal drug delivery
US20070184096A1 (en) * 2005-12-28 2007-08-09 Alza Corporation Stable Therapeutic Formulations
US7344499B1 (en) 1998-06-10 2008-03-18 Georgia Tech Research Corporation Microneedle device for extraction and sensing of bodily fluids
US20080125743A1 (en) * 2006-11-28 2008-05-29 Yuzhakov Vadim V Tissue Conforming Microneedle Array and Patch For Transdermal Drug Delivery or Biological Fluid Collection
US7556821B2 (en) 2004-05-13 2009-07-07 Alza Corporation Apparatus and method for transdermal delivery of parathyroid hormone agents
US7579013B2 (en) 2003-06-30 2009-08-25 Alza Corporation Formulations for coated microprojections containing non-volatile counterions
US20100180894A1 (en) * 2009-01-15 2010-07-22 Andrew Jones Delivery device and related methods
US8116860B2 (en) 2002-03-11 2012-02-14 Altea Therapeutics Corporation Transdermal porator and patch system and method for using same
US8430805B2 (en) 2006-10-02 2013-04-30 Emkinetics, Inc. Method and apparatus for magnetic induction therapy
US8588884B2 (en) 2010-05-28 2013-11-19 Emkinetics, Inc. Microneedle electrode
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US9339641B2 (en) 2006-01-17 2016-05-17 Emkinetics, Inc. Method and apparatus for transdermal stimulation over the palmar and plantar surfaces
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Cited By (109)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3072122A (en) * 1959-01-15 1963-01-08 Rosenthal Sol Roy Package for transcutaneous injection
US3034507A (en) * 1960-05-10 1962-05-15 American Cyanamid Co Intracutaneous injection device
US3074403A (en) * 1960-05-17 1963-01-22 American Cyanamid Co Intracutaneous injector with capillary gap
US3136314A (en) * 1960-08-01 1964-06-09 Kravitz Harvey Vaccinating devices
US3167073A (en) * 1962-01-16 1965-01-26 Rosenthal Sol Roy Transcutaneous injection device
US3221739A (en) * 1962-03-26 1965-12-07 Rosenthal Sol Roy Injection device
US3246647A (en) * 1962-07-23 1966-04-19 American Cyanamid Co Disposable intracutaneous injector
US3291129A (en) * 1962-08-10 1966-12-13 Burelle Pierre Laurent Raymond Scarificator for use in vaccination, skin tests, or the like
US3221740A (en) * 1962-08-31 1965-12-07 Rosenthal Sol Roy Injection device
US3703890A (en) * 1970-08-10 1972-11-28 Milton A Saunders Jr Skin patch test device
US3882999A (en) * 1972-03-09 1975-05-13 Lester R Wellman Opener/re-closer for sealed containers
EP0081975A2 (en) * 1981-12-14 1983-06-22 Nicholas H. Maganias Device and method for allergy testing
EP0081975A3 (en) * 1981-12-14 1983-12-28 Nicholas H. Maganias Device and method for allergy testing
US4802493A (en) * 1981-12-14 1989-02-07 Maganias Nicholas H Device and method for allergy testing
US5099857A (en) * 1987-05-29 1992-03-31 Northern Sydney Area Health Service Medical testing device with calibrated indicia
US5104620A (en) * 1990-07-30 1992-04-14 Wiley Fred R Disposable allergy skin testing kit
US20070118070A1 (en) * 1996-06-18 2007-05-24 Cormier Michel J Device with anchoring elements for transdermal delivery or sampling of agents
US6219574B1 (en) 1996-06-18 2001-04-17 Alza Corporation Device and method for enchancing transdermal sampling
US20020016562A1 (en) * 1996-06-18 2002-02-07 Michel J. N. Cormier Device and method for enhancing transdermal flux of agents being delivered or sampled
US7184826B2 (en) 1996-06-18 2007-02-27 Alza Corporation Device and method for enhancing transdermal flux of agents being delivered or sampled
US20040236271A1 (en) * 1997-12-10 2004-11-25 Felix Theeuwes Device and method for enhancing transdermal agent flux
US6083196A (en) * 1997-12-11 2000-07-04 Alza Corporation Device for enhancing transdermal agent flux
US6953589B1 (en) 1997-12-11 2005-10-11 Alza Corporation Device for enhancing transdermal agent flux
US6322808B1 (en) 1997-12-11 2001-11-27 Alza Corporation Device for enhancing transdermal agent flux
US7344499B1 (en) 1998-06-10 2008-03-18 Georgia Tech Research Corporation Microneedle device for extraction and sensing of bodily fluids
US6503231B1 (en) 1998-06-10 2003-01-07 Georgia Tech Research Corporation Microneedle device for transport of molecules across tissue
US20100312191A1 (en) * 1998-06-10 2010-12-09 Georgia Tech Research Corporation Microneedle Devices and Methods of Manufacture and Use Thereof
US6334856B1 (en) 1998-06-10 2002-01-01 Georgia Tech Research Corporation Microneedle devices and methods of manufacture and use thereof
US8708966B2 (en) 1998-06-10 2014-04-29 Georgia Tech Research Corporation Microneedle devices and methods of manufacture and use thereof
US20020138049A1 (en) * 1998-06-10 2002-09-26 Allen Mark G. Microneedle devices and methods of manufacture and use thereof
US7226439B2 (en) 1999-06-04 2007-06-05 Georgia Tech Research Corporation Microneedle drug delivery device
US6611707B1 (en) 1999-06-04 2003-08-26 Georgia Tech Research Corporation Microneedle drug delivery device
US8257324B2 (en) 1999-06-04 2012-09-04 Georgia Tech Research Corporation Microneedle drug delivery device
US20070225676A1 (en) * 1999-06-04 2007-09-27 Prausnitz Mark R Microneedle drug delivery device
US20050137531A1 (en) * 1999-11-23 2005-06-23 Prausnitz Mark R. Devices and methods for enhanced microneedle penetration of biological barriers
US6743211B1 (en) 1999-11-23 2004-06-01 Georgia Tech Research Corporation Devices and methods for enhanced microneedle penetration of biological barriers
US6443307B1 (en) * 2000-01-25 2002-09-03 Michael D. Burridge Medication dispenser with an internal ejector
US20040039342A1 (en) * 2000-06-08 2004-02-26 Jonathan Eppstein Transdermal integrated actuator device, methods of making and using same
US20050197308A1 (en) * 2000-07-21 2005-09-08 Smithkline Beecham Biologicals S.A. Vaccines
US7537795B2 (en) 2000-10-26 2009-05-26 Alza Corporation Transdermal drug delivery devices having coated microprotrusions
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