High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances

• US 8,048,017 B2
• Filed: 10/31/2007
• Issued: 11/01/2011
• Est. Priority Date: 05/18/2005
• Status: Active Grant

• Current Assignee: Bai Xu
• Original Assignee: Bai Xu
• Inventors: Xu, Bai
• Primary Examiner(s): KOHARSKI, CHRISTOPHER
• Application Number:
  US11/932,593
• Publication Number:
  US 20080051695A1
• Time in Patent Office: 1,462 Days
• Field of Search: 604 20- 22, 606/185
• US Class Current: 604/22
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles

Abstract

High-aspect-ratio microdevices comprising microneedles, microknives and microblades and their manufacturing methods are disclosed. These devices can be used for the delivery of therapeutic agents across the skin or other tissue barriers to allow chemical and biological molecules getting into the circulation systems. The microneedles can also be used to withdraw body fluids for analysis of clinically relevant species when the device has an integrated body fluid sensor or sensor array in the vicinity of microneedles.

Claims

1. A method of delivering an active agent to a human being, comprising

selecting a site of skin for delivery of the active agent,

pushing a plurality of microneedles attached to a substrate to the selected site,

allowing the microneedles to pierce through the outer layer of the site of the skin,

immediately removing the plurality of microneedles after piercing the site of skin to generate a plurality of microscale or nanoscale transdermal conduits lined with tissue displaced by the microneedles,

applying a skin patch comprising the active agent to the site of skin, and

causing the active agent dispersed in a medium on the skin patch to be delivered transdermally through the plurality of microscale or nanoscale conduits into the human being,

wherein the microneedles are solid microneedles having an aspect ratio of about 10:

1 or higher.

2. The method of claim 1, wherein the skin patch comprise the active agent dispersed in an active medium containing water content.

3. The method of claim 1, wherein the active agent is a therapeutic agent, a diagnostic agent, or a cosmetic agent, or a combination thereof.

4. The method of claim 3, wherein the therapeutic agent is selected from the group consisting of antibiotics, hormones, steroids, anti-inflammatory drugs, protein drugs, drugs, recombinant Erythropoietin (rhEPO), Taxol®

, Interferon-alpha-1b, Interferon beta, Interferon gamma, Emla®

, Fluorouracil, Lidocaine, Salicylic acid, Pureriran, eflornithine hydrochloride, spironolactone, flutamide, insulin, nanoparticle drugs, Epidural, recombinant human parathyroid hormone, growth hormone, thyroid, cortisol, estrogen, progesterone, and testosterone and combinations thereof.

5. The method of claim 3, wherein the cosmetic agent is selected from the group consisting of hyaluronic acid and its derivatives, acetyl hexapeptide-3, vitamin A, vitamin C, vitamin E, alpha-hydroxyacids, and hormones.

6. The method of claim 3, wherein the active agent is a natural or synthesized vaccine selected from the group consisting of vaccines, protein vaccines, peptide vaccines, gene vaccines and DNA vaccines against influenza (flu), diphtheria, tetanus, pertussis (DTaP), measles, mumps, rubella (MMR), hepatitis B, polio, haemophilus influenzae type b, chickenpox, tuberculosis, anthrax, yellow fever, rabies, AIDS, cancers, meningococcus, SARS and cholera.

7. The method of claim 3, wherein the diagnostic agent is selected from the group consisting of quantum dots, functionalized nanoparticles, magnetic particles or a combination of thereof.

8. The method of claim 1, wherein the combination of microneedles and the skin patch provides for controlled release of the active agent.

9. The method of claim 1, wherein the human being has one or more medical conditions selected from AIDS, breast cancer, melanoma, liver cancer, lung cancer, blood cancer, pituitary tumors, other cancers, flu, infection, blood disease, cardiac disease, back pain, neck pain, body pain, general pain, arthritis, osteoporosis, headache, depression, smoke, alcoholic, overweight and obesity, menopause, facial hair growth, balding, polycystic ovary syndrome, need of inoculation, need of anesthetics and dermal diseases.

10. The method of claim 1, wherein the human being has one or more cosmetic conditions selected from skin aging, skin wrinkle, dark spot, skin discoloration, moisturizing, skin lightening, skin whitening, skin firming, skin lifting, acne, wart, infection, irritation, dry skin and oily skin.

11. The method of claim 1, wherein the microneedles are fabricated using an anisotropic etch to define the size of the microneedles, followed by an orientation dependent etch using a solution of potassium hydroxide or tetramethyl ammonium hydroxide or sodium hydroxide solution or a combination thereof, at a temperature between 20 to 90 degree and a concentration between 10% to 80%.

12. A method of delivering an active agent to a human being, comprising

selecting a site of skin for delivery of the active agent,

slicing a plurality of microdevices on the skin surface of the selected site,

allowing the microdevices to cut through the outer layer of the skin on the selected site,

immediately removing the plurality of microdevices after piercing the selected skin site to generate a plurality of microscale or nanoscale transdermal conduits lined with tissue displaced by the microdevice,

applying a skin patch comprising the active agent to the site of skin, and

causing the active agent dispersed in a medium on the skin patch to be delivered

transdermally through the plurality of microscale or nanoscale conduits into the human being,

wherein the microdevices are solid microblades or solid microknives, or a combination thereof, and

wherein the microdevices have an nanoscale edge.

13. The method of claim 12, wherein the skin patch comprise the active agent dispersed in an active medium containing water content.

14. The method of claim 12, wherein the active agent is a therapeutic agent, a diagnostic agent, or a cosmetic agent.

15. The method of claim 14, wherein the therapeutic agent is selected from the group consisting of antibiotics, hormones, steroids, anti-inflammatory drugs, protein drugs, DNA drugs, recombinant Erythropoietin (rhEPO), Taxol®

, Interferon-alpha-1b, Interferon beta, Interferon gamma, Emla®

, Fluorouracil, Lidocaine, Salicylic acid, Pureriran, eflornithine hydrochloride, spironolactone, flutamide, insulin, nanoparticle drugs, Epidural, recombinant human parathyroid hormone, growth hormone, thyroid, cortisol, estrogen, progesterone, testosterone and combinations thereof.

16. The method of claim 14, wherein the cosmetic agent is selected from the group consisting of hyaluronic acid and its derivatives, acetyl hexapeptide-3, vitamin A, vitamin C, vitamin E, alpha-hydroxyacids, and hormones.

17. The method of claim 14, wherein the bioactive agent is a natural or synthesized vaccine selected from the group consisting of vaccines, protein vaccines, peptide vaccines, gene vaccines and DNA vaccines against influenza (flu), diphtheria, tetanus, pertussis (DTaP), measles, mumps, rubella (MMR), hepatitis B, polio, haemophilus influenzae type b, chickenpox, tuberculosis, anthrax, yellow fever, rabies, AIDS, cancers, meningococcus, SARS and cholera.

18. The method of claim 14, wherein the diagnostic agent is selected from the group consisting of quantum dots, functionalized nanoparticles, magnetic particles or a combination of thereof.

19. The method of claim 12, wherein the microdevice provides for controlled release of the bioactive agent.

20. The method of claim 12, wherein the human being has one or more medical conditions selected from AIDS, breast cancer, melanoma, liver cancer, lung cancer, blood cancer, pituitary tumors, other cancers, flu, infection, blood disease, cardiac disease, back pain, neck pain, body pain, general pain, arthritis, osteoporosis, headache, depression, smoke, alcoholic, overweight and obesity, menopause, facial hair growth, balding, polycystic ovary syndrome, need of inoculation, need of anesthetics and dermal diseases.

21. The method of claim 12, wherein the microdevices are fabricated using an anisotropic etch to define the size of the microneedles, followed by an orientation dependent etch using a solution of potassium hydroxide or tetramethyl ammonium hydroxide or sodium hydroxide solution or a combination thereof, at a temperature between 20 to 90 degree and a concentration between 10% to 80%.

22. The method of claim 12, wherein the human being has one or more cosmetic conditions selected from skin aging, skin wrinkle, dark spot, skin discoloration, moisturizing, skin lightening, skin whitening, skin firming, skin lifting, acne, wart, infection, irritation, dry skin and oily skin.