WO1997004832B1 - Enhanced transdermal transport using ultrasound - Google Patents
Enhanced transdermal transport using ultrasoundInfo
- Publication number
- WO1997004832B1 WO1997004832B1 PCT/US1996/012244 US9612244W WO9704832B1 WO 1997004832 B1 WO1997004832 B1 WO 1997004832B1 US 9612244 W US9612244 W US 9612244W WO 9704832 B1 WO9704832 B1 WO 9704832B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ultrasound
- molecules
- skin
- administered
- frequency
- Prior art date
Links
- 238000002604 ultrasonography Methods 0.000 title claims abstract 20
- 230000002708 enhancing Effects 0.000 claims abstract 15
- 239000003814 drug Substances 0.000 claims abstract 8
- 229940079593 drugs Drugs 0.000 claims abstract 8
- 239000003623 enhancer Substances 0.000 claims abstract 4
- 239000011859 microparticle Substances 0.000 claims abstract 4
- 210000004369 Blood Anatomy 0.000 claims abstract 3
- 239000008280 blood Substances 0.000 claims abstract 3
- 239000000126 substance Substances 0.000 claims abstract 3
- 210000001124 Body Fluids Anatomy 0.000 claims abstract 2
- 239000010839 body fluid Substances 0.000 claims abstract 2
- 239000000969 carrier Substances 0.000 claims abstract 2
- 230000005684 electric field Effects 0.000 claims abstract 2
- 238000004520 electroporation Methods 0.000 claims abstract 2
- 239000002502 liposome Substances 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims 11
- 210000003491 Skin Anatomy 0.000 claims 9
- OYHQOLUKZRVURQ-IXWMQOLASA-N Linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 claims 2
- 239000012491 analyte Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 239000000463 material Substances 0.000 claims 2
- 230000003204 osmotic Effects 0.000 claims 2
- 210000003722 Extracellular Fluid Anatomy 0.000 claims 1
- 239000000232 Lipid Bilayer Substances 0.000 claims 1
- 229920001963 Synthetic biodegradable polymer Polymers 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- 150000002433 hydrophilic molecules Chemical class 0.000 claims 1
- 235000020778 linoleic acid Nutrition 0.000 claims 1
- 210000004880 lymph fluids Anatomy 0.000 claims 1
- 230000035515 penetration Effects 0.000 claims 1
- 210000002751 Lymph Anatomy 0.000 abstract 1
- 238000005259 measurement Methods 0.000 abstract 1
- 239000003607 modifier Substances 0.000 abstract 1
- 230000035699 permeability Effects 0.000 abstract 1
Abstract
Several means for enhancing transdermal transport of drugs and analytes have been developed, including the use of low frequence ultrasound, chemical modifiers of permeability and/or cavitation, iontophoresis and/or electroporation (electric fields), pressure and/or vacuum (physical enhancers), and magnetic force fields. Applications of low-frequency (approximately 20 KHz to 1 MHz) ultrasound enhances transdermal transport of drugs and measurements of the concentration of analytes in body fluids such as blood or lymph. Delivery can be further enhanced or controlled through the use of carriers for the drugs, such as liposomes or microparticles, using a wide range of ultrasound frequency ranges and intensities. The microparticles are preferably small, and may have surfaces with increased hydrophilicity or lipophilicity to further enhance transport.
Claims
1. A use of an apparatus for enhancing transport of molecules across the skin comprising means for applying ultrasound to the skin, wherein the ultrasound is application at a frequency of between 20 kHz and less than 1 MHz for a period of time effective to transport the molecules through the skin.
2. The use of claim 1 wherein the molecules are drugs to be administered to a person in need thereof.
3. The use of claim 1 wherein the molecules are analytes present in blood, lymph or interstitial fluid.
4. The use of claim 1 wherein the frequency is between 20 and 45 kHz.
5. The use of claim 1 wherein the intensity is between zero and 1 W/cm2.
6. The use of claim 5 wherein the intensity is between 12.5 mW/cm2 and 225 mW/cm2.
7. A method of using the apparatus of any of claims 1-6 to enhance transfer of molecules through the skin by applying ultrasound at a frequency of between 20 kHz and less than 1 MHz for a period of time effective to transport the molecules through the skin.
8. A method for extracting an analyte to be measured in a blood or body fluid sample comprising applying at an appropriate site for extraction of a sample an effective amount of ultrasound and collecting the extracted sample, wherein the ultrasound is applied at a frequency between 20 kHz and less than 10 MHz.
9. The method of claim 8 wherein the ultrasound is applied at a frequency of between 20 kH and less than 1 MHz.
10. An apparatus for enhancing transdermal transport of molecules comprising means for administering to the skin an effective amount of ultrasound for transdermal transport of molecules in combination with an enhancer selected from the group consisting of chemical enhancer combinations of agents enhancing solubility of the molecules to be transported with agents enhancing the fluidity of lipid bilayers, mechanical force fields, osmotic force fields, magnetic force fields and electric force fields.
11. The apparatus of claim 9 wherein the ultrasound is administered at a frequency of less than 2.5 MHz.
12. The apparatus of claim 9 wherein the ultrasound is administered at a frequency of 1 MHz or less.
13. The apparatus of claim 9 wherein the combination is linoleic acid in an ethanol solution.
14. The apparatus of claim 9 wherein the ultrasound is administered in combination with an electric force field selected from the group consisting of electroporation and iontophoresis .
15. The apparatus of claim 13 wherein the electric field is pulsed.
16. The apparatus of claim 9 wherein the ultrasound is administered in combination with a magnetic force field.
17. The apparatus of claim 9 wherein the ultrasound is administered in combination with a mechanical force field created by pressure or vacuum.
18. The apparatus of claim 9 wherein the ultrasound is administered in combination with an osmotic force field.
19. The apparatus of claim 9 wherein the ultrasound is administered in combination with chemical enhancers and mechanical forces.
20. The apparatus of claim 1 wherein the molecules to be transported are drugs the patient is in need of.
21. The apparatus of claim 9 wherein the compound to be transported is an analyte to be measured.
22. The apparatus of claim 9 wherein the ultrasound is pulsed.
23. The method of use of the apparatus of any of claims 9-21 in enhancing transport of molecules through the skin.
22. A composition for enhancing delivery of drugs across the skin comprising drug encapsulated in a liposome or polymeric carrier for application to the skin and applying ultrasound for a period of time effective to deliver to the patient a desired drug dosage.
AMENDED S
23. The composition of claim 22 wherein the microparticle is coated with a lipophilic or hydrophilic material enhancing transdermal penetration.
24. The composition of claim 22 wherein the material is a hydrophilic molecule couple to a synthetic biodegradable polymer forming the microparticle.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE69624668T DE69624668T2 (en) | 1995-07-25 | 1996-07-25 | IMPROVED TRANSDERMAL TRANSPORTATION USING ULTRASOUND |
| AT96925491T ATE227146T1 (en) | 1995-07-25 | 1996-07-25 | IMPROVED TRANSDERMAL TRANSPORT USING ULTRASOUND |
| JP9507744A JPH10509632A (en) | 1995-07-25 | 1996-07-25 | Enhanced transdermal delivery using ultrasound |
| AU65987/96A AU725269B2 (en) | 1995-07-25 | 1996-07-25 | Enhanced transdermal transport using ultrasound |
| EP96925491A EP0781150B1 (en) | 1995-07-25 | 1996-07-25 | Enhanced transdermal transport using ultrasound |
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US626,021 | 1984-06-29 | ||
| US08/507,060 US6002961A (en) | 1995-07-25 | 1995-07-25 | Transdermal protein delivery using low-frequency sonophoresis |
| US08/511,583 US5814599A (en) | 1995-08-04 | 1995-08-04 | Transdermal delivery of encapsulated drugs |
| US08/574,377 US5947921A (en) | 1995-12-18 | 1995-12-18 | Chemical and physical enhancers and ultrasound for transdermal drug delivery |
| US574,377 | 1996-04-01 | ||
| US08/626,021 US6041253A (en) | 1995-12-18 | 1996-04-01 | Effect of electric field and ultrasound for transdermal drug delivery |
| US511,583 | 1996-04-01 | ||
| US507,060 | 1996-04-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1997004832A1 WO1997004832A1 (en) | 1997-02-13 |
| WO1997004832B1 true WO1997004832B1 (en) | 1997-04-03 |
Family
ID=27504462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1996/012244 WO1997004832A1 (en) | 1995-07-25 | 1996-07-25 | Enhanced transdermal transport using ultrasound |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0781150B1 (en) |
| JP (1) | JPH10509632A (en) |
| AT (1) | ATE227146T1 (en) |
| AU (1) | AU725269B2 (en) |
| CA (1) | CA2200984A1 (en) |
| DE (1) | DE69624668T2 (en) |
| WO (1) | WO1997004832A1 (en) |
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| US9033950B2 (en) | 2003-10-24 | 2015-05-19 | Nitto Denko Corporation | Method for transdermal delivery of permeant substances |
| US9572527B2 (en) | 2007-04-27 | 2017-02-21 | Echo Therapeutics, Inc. | Skin permeation device for analyte sensing or transdermal drug delivery |
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1996
- 1996-07-25 EP EP96925491A patent/EP0781150B1/en not_active Expired - Lifetime
- 1996-07-25 DE DE69624668T patent/DE69624668T2/en not_active Expired - Fee Related
- 1996-07-25 JP JP9507744A patent/JPH10509632A/en active Pending
- 1996-07-25 AT AT96925491T patent/ATE227146T1/en not_active IP Right Cessation
- 1996-07-25 CA CA002200984A patent/CA2200984A1/en not_active Abandoned
- 1996-07-25 AU AU65987/96A patent/AU725269B2/en not_active Ceased
- 1996-07-25 WO PCT/US1996/012244 patent/WO1997004832A1/en active IP Right Grant
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8870810B2 (en) | 1998-12-18 | 2014-10-28 | Echo Therapeutics, Inc. | Method and apparatus for enhancement of transdermal transport |
| US9033950B2 (en) | 2003-10-24 | 2015-05-19 | Nitto Denko Corporation | Method for transdermal delivery of permeant substances |
| US9572527B2 (en) | 2007-04-27 | 2017-02-21 | Echo Therapeutics, Inc. | Skin permeation device for analyte sensing or transdermal drug delivery |
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