Transdermal drug delivery devices having coated microprotrusions
First Claim
1. A device for transdermally delivering a pharmacologically active agent, the device comprising:
- a member having a plurality of stratum corneum-piercing microprotrusions and a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 milligrams, said agent having aqueous solubility at about 25°
C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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Accused Products
Abstract
A device (12) and method are provided for percutaneous transdermal delivery of a potent pharmacologically active agent. The agent is dissolved in water to form an aqueous coating solution having an appropriate viscosity for coating extremely tiny skin piercing elements (10). The coating solution is applied to the skin piercing elements (10) using known coating techniques and then dried. The device (12) is applied to the skin of a living animal (e.g., a human), causing the microprotrusions (10) to pierce the stratum corneum and deliver a therapeutically effect dose of the agent to the animal.
93 Citations
46 Claims
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1. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions and a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 milligrams, said agent having aqueous solubility at about 25°
C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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2. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions and a dry coating only on one or more of said microprotrusions;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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3. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusion being adapted to pierce through the stratum corneum to a depth of less than about 500 micrometers; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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4. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
said coating having a thickness equal to or less than the thickness of the microprotrusions;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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5. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having a length of less than 500 micrometers and a thickness of less than 25 micrometers; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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6. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusions having been formed by etching said plurality of microprotrusions from a thin sheet and folding the microprotrusions out of a plane of the sheet; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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7. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions and a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
said pharmacologically active agent being sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises; and
wherein the pharmacologically active agent is selected from the group consisting of adrenocortiocotropic hormone (ACTH (1-24)), calcitonin, desmopressin, leutinizing hormone releasing hormone (LHRH), goserelin, leuprolide, buserelin, triptorelin, other LHRH analogs, parathyroid hormone (PTH), vasopressin, deamino [Val4, D-Arg8] arginine vasopressin, interferon alpha, interferon beta, interferon gamma, follicle stimulating hormone (FSH), erythropoietin (EPO), granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin-10 (IL-10), glucagon, growth regulatory factor (GRF), analogs thereof and pharmaceutically acceptable salts thereof.
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8. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of the pharmacologically active agent desmopressin;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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9. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having been applied by dip coating;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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10. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having been applied by spray coating;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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11. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having been applied by spray coating;
said spray comprising droplets having a volume of about 10 picoliters to about 200 picoliters;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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12. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry non-contiguous coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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13. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 0.25 milligrams, said agent having aqueous solubility at about 25°
C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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14. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25°
C. of less than about 50 centipoises.
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15. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having a thickness over a surface of said member of less than about 50 micrometers;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 mg/ml and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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16. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent, said coating having a thickness over a surface of said member of less than about 25 micrometers;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 milligrams/milliliter and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoises.
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17. A device for transdermally delivering a pharmacologically active agent, the device comprising:
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a member having a plurality of stratum corneum-piercing microprotrusions; and
a dry coating on said member;
said coating, before drying, comprising an aqueous solution of an amount of a pharmacologically active agent and an adjuvant;
wherein said pharmacologically active agent is sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg, said agent having aqueous solubility at about 25°
C. of greater than about 50 mg/mL and said aqueous solution having a viscosity at about 25°
C. of less than about 500 centipoise.
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18-37. -37. (canceled)
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38. A method of transdermally delivering a pharmacologically active agent to a patient, comprising the steps of:
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providing a microprotrusion member having a plurality of stratum corneum-piercing microprotrusions, said microprotrusion member having a coating disposed thereon, said coating including at least one pharmacologically active agent, said pharmacologically active agent being sufficiently potent to be therapeutically effective when administered in an amount less than about 1 mg; and
applying said microprotrusion member to a skin site on the patient, whereby said plurality of stratum corneum-piercing microprotrusions pierce the stratum corneum and deliver said pharmacologically active agent to the patient, wherein said delivered pharmacologically active agent has improved pharmacokinetics compared to pharmacokinetics after subcutaneous injection. - View Dependent Claims (39, 40, 41, 42, 43, 44, 45, 46)
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Specification