Transdermal administration method of protein or peptide drug and its administration device thereof

• US 5,250,023 A
• Filed: 10/29/1990
• Issued: 10/05/1993
• Est. Priority Date: 10/27/1989
• Status: Expired due to Term

• Current Assignee: Korea Research Institute of Chemical Technology
• Original Assignee: Korean Research Institute On Chemical Technology
• Inventors: Lee, Hai Bang, Shin, Bung Chul
• Primary Examiner(s): Pellegrino, Stephen C.
• Assistant Examiner(s): RAFA, MICHAEL
• Application Number:
  US07/604,498
• Time in Patent Office: 1,072 Days
• Field of Search: 604/20, 604/46, 604/49, 128/743, 128/798, 128/898, 128/802, 128/803, 606/131
• US Class Current: 604/20
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61N 1/0432 Anode and cathode
• CPC Class Codes: A61N 1/0448 Drug reservoir
• CPC Class Codes: A61N 1/306 Arrangements where at least part of the apparatus is introduced into the body

Abstract

A transdermal administration method for protein or peptide drug that contacting and ionizing a protein or peptide drug immersed in hydrophilic polymer with ionizing solvent composition, and forming the drug pathway on epidermis by plural skin needles or treating the skin by a razor, and transferring the above ionized drug into the skin by electric force.

Claims

1. An integration-type transdermal administration device of a patch-type which may be attached to the skin comprising the following:

A) solvent reservoir (2) for ionizing solvent and polyelectrolyte, injected from the outside through a solvent inlet (7),

B) drug reservoir (3) comprising drug immersed water-swellable polymer located opposite from the solvent inlet such that the solvent reservoir (2) is interposed between the drug reservoir and the inlet, with a lower portion support (5) made of non-woven fabric, including plural skin needles (4) vertically dispersed in a fixed state on said support and said support (5) is interposed between the drug reservoir and the skin needles,

C) stacking-structural adhesive layer(6) formed around the supporter of the drug reservoir.

2. The integration-type transdermal administration device according to claim 1, wherein the solvent reservoir (2) and drug reservoir(3) are, constructed from one or more of the polymers from the group consisting of polyacrylamide, carboxymethylcellulose, polyvinylimine, polyacrylate, alginate, karaya gum, and gelatin.

3. The device according to claim 1 wherein the drug reservoir contains a drug selected from the group consisting of captopril, bradykinin, atriopeptin, calcitoningene factor, cholecystokinin (CCK-8, 32), β

-endorphin, nerve growth factor, melanocyte inhibitor -I, gastrin antagonist, neuro-tension, somatotatin, interferon, cyclosporin, encephalins, albumin, insulin, vasopressins, oxytocin, growth hormone, LH (Leutinizing Hormone) and TRH (Thyrotropin Releasing Hormone).

4. The device according to claim 1 wherein the ionizing solvent in the solvent reservoir contains 1 to 50% by volume of solvents selected from the group consisting of salt buffer solutions of phenol derivatives, acetic acid, hydrochloric acid, ammonia water, and caustic soda.

5. The device according to claim 1 wherein the polyelectrolyte contained in the solvent reservoir contains 1 to 30% by volume of one or more polyelectrolytes selected from the group consisting of soluble or insoluble polyacrylamide, polyvinylimine, quadravalent ammonium, polyacrylate, carboxymethyl cellulose and alginate, based on 100% by volume of water.

6. The administration device according to claim 1, wherein said support (5) is mechanically attached or thermally bonded to the reservoir (2) and the needles (4) are thermally bonded to the support (5).

7. A separation-type transdermal administration kit of the patch-type which may be attached to the skin comprising the following:

a) electrode (11) located uppermost and furthest from the place of skin attachment;

b) solvent reservoir (12) for ionizing solvent and polyelectrolyte located below the electrode (11);

c) semipermeable membrane (18) which may have a molecular weight cut off range in the range of from 200 to 20,000 which forms the lower portion of the solvent reservoir (12);

d) drug reservoir (13) comprising a drug-immersed water swellable polymer located below the semipermeable membrane (18);

e) patch body (30) comprising an adhesive layer (16) formed around the drug reservoir (13); and

f) skin needles (14) fixed vertically in a skin needle plate (15) separated from the patch body.

8. A transdermal administration kit as claimed in claim 7, in which the semipermeable membrane (18) is selected from the group consisting of polypropylene, cellulose, and ethylene vinylacetate.

9. The kit according to claim 7 wherein the drug reservoir contains a drug selected from the group consisting of captopril, bradykinin, atriopeptin, calcitoningene factor, cholecystokinin (CCK-8, 32), β

-endorphin, nerve growth factor, melanocyte inhibitor -I, gastrin antagonist, neuro-tension, somatotatin, interferon, cyclosporin, encephalins, albumin, insulin, vasopressins, oxytocin, growth hormone, LH (Leutinizing Hormone) and TRH (Thyrotropin Releasing Hormone).

10. The kit according to claim 7 wherein the ionizing solvent in the solvent reservoir contains 1 to 50% by volume of solvents selected from the group consisting of salt buffer solutions of phenol derivatives, acetic acid, hydrochloric acid, ammonia water, and caustic soda.

11. The kit according to claim 7 wherein the polyelectrolyte contained in the solvent reservoir contains 1 to 30% by volume of one or more polyelectrolytes selected from the group consisting of soluble or insoluble polyacrylamide, polyvinylimine, quadravalent ammonium, polyacrylate, carboxymethyl cellulose and alginate, based on 100% by volume of water.

12. The administration kit according to claim 7, wherein said needle plate and skin needles are attached to the drug reservoir and positioned opposite from the electrode.

13. The administration kit according to claim 7, wherein said needle plate comprises steeo or non-woven fabric and the needles (14) are thermally bonded to the support (5).

14. A transdermal administration method for a peptide drug comprising the steps of:

i) contacting the drug immersed in polyelectrolyte with ionizing solvent composition wherein the drug is ionized,

ii) forming the drug pathway on the skin epidermis by penetrating a plurality of skin needles into the skin epidermis at a treatment site

iii) transferring the ionized drug into the skin at the treatment site by iontophoretic force.

15. The transdermal administration method according to claim 14, wherein the drug is selected from the group consisting of Captopril, bradykinin, atriopeptin, calcitonin gene factor, cholecystokinin (CCK-8, 32), β

-endorphin, nerve growth factor, melanocyte inhibitor-I, gastrin antagonist, neuro-tension, somatotatin, interferon, cyclosporin, encephalins, albumin, insulin, vasopressins, oxytocin, growth hormone, LH(Leutinizing Hormone), TRH(Thyrotropin Releasing Hormone).

16. The transdermal administration method according to claim 14,

wherein the ionizing solvent contains 1 to 50% by volume of solvents selected from the group consisting of salt buffer solutions of phenol derivatives, acetic acid, hydrochloric acid, ammonia water, and caustic soda;

based on 100% by volume of water.

17. The transdermal administration method according to claim 14 wherein the polyelectrolyte is used for adjusting pH in drug solution and electrolytic medium, and contains 1 to 30% by volume of one or more polyelectrolytes selected from the group consisting of soluble or insoluble polyacrylamide, polyvinylimine, quadravalent ammonium, polyacrylate, carboxymethyl cellulose and alginate, based on 100% by volume of water.

18. A transdermal administration method for a drug selected from the group consisting of captopril, bradykinin, atriopeptin, calcitonin gene factor, cholecystokinin (CCK-8, 32), β

-endorphin, nerve growth factor, melanocyte inhibitor -I, gastrin antagonist, neuro-tension, somatotatin, interferon, cyclosporin, encephalins, albumin, insulin, vasopressins, oxytocin, growth hormone, LH (Luetinizing Hormone) and TRH (Thyrotropin Releasing Hormone), comprising the steps of;

i) contacting the drug immersed in a polyelectrolyte with an ionizing solvent composition wherein,

the ionizing solvent contains 1 to 50% by volume of solvents selected from the group consisting of salt buffer solutions of phenol derivatives, acetic acid, hydrochloric acid, ammonia water, and caustic soda; and

the polyelectrolyte contains 1 to 30% by volume of one or more polyelectrolytes selected from the group consisting of soluble or insoluble polyacrylamide, polyvinylimine, quadravalent ammonium, polyacrylate, carboxymethyl cellulose and alginate, based on 100% by volume of water;

ii) forming the drug pathway on the skin by micro-piercing by penetrating a plurality of skin needles into the skin epidermis at a treatment site; and

iii) transferring the ionized drug into the skin at the treatment site by iontophoretic force.

19. The method according to claim 18 further comprising:

abrading the skin in the area of administration prior to forming the drug pathway of step (ii).