Transdermal therapeutic system for the administration of peptides

Patent metadata

Field	Value
Publication number	US-10471021-B2
Application number	US-201815867050-A
Country	US
Kind code	B2
Filing date	Jan 10, 2018
Priority date	Dec 4, 2009
Publication date	Nov 12, 2019
Grant date	Nov 12, 2019

Abstract

The invention relates to a transdermal therapeutic system (TTS), which is suited for the administration of a peptide to a patient through skin treated with ablation. The transdermal therapeutic system includes a back layer and an active substance-containing layer that contains at least one peptide and a carrier substance, preferably as a textile web material.

First claim

That which is claimed:

1. A method of fertility treatment comprising application of first and second transdermal therapeutic systems, each of the first and second transdermal therapeutic systems comprising (i) a backing layer; (ii) an active ingredient layer; (iii) a pressure-sensitive adhesive and (iv) a removable protective sheet, said method comprising,
in a first step, ablatively treating the skin of a female patient by a laser skin ablation technique,
applying the first transdermal therapeutic system with a GnRH agonist as an active ingredient in the active ingredient layer to the skin location treated in the first step and leaving the first transdermal therapeutic system with the GnRH agonist at the skin location treated in the first step for a prolonged time period, the first transdermal therapeutic system delivering the GnRH agonist transdermally to the female patient;
ablatively treating a second skin location on the female patient by a laser skin ablation technique, and
at said second skin location, applying the second transdermal therapeutic system with a follicle-stimulating hormone as an active ingredient in the active ingredient layer, thereby administering follicle stimulating hormone transdermally to bring about the formation of follicles in the female patient.

2. The method as claimed in claim 1 , wherein said method further comprises measuring the female patient's endogenous follicle-stimulating hormone level during GnRH agonist delivery to determine if the level is below a target value.

3. The method as claimed in claim 2 , wherein the target value is 10 mIU/ml and said method further comprises ablatively treating a third skin location of the female patient by a laser skin ablation technique and applying a third transdermal therapeutic system with a GnRH agonist as active ingredient to the third skin location if the female patient's endogenous follicle-stimulating hormone was above 10 mIU/ml subsequent to administration of the first transdermal therapeutic system.

4. The method as claimed in claim 1 , wherein said method further comprises monitoring the formation of follicles in the female patient.

5. The method as claimed in claim 4 , wherein said monitoring comprises investigating via ultrasound.

6. The method as claimed in claim 1 , wherein said method further comprises removing formed follicles from the female patient, fertilizing the follicles in vitro, and transferring the fertilized follicles into the female patient or a surrogate mother.

7. The method as claimed in claim 1 , wherein said laser skin ablation techniques are performed immediately before applying the first and second transdermal therapeutic systems onto the treated first and second skin locations.

8. The method as claimed in claim 1 , wherein the first and second transdermal therapeutic systems are applied to the respective ablatively treated first and second skin locations such that the respective active ingredient layers lie directly above the respective ablatively treated first and second skin locations.

9. The method as claimed in claim 1 , wherein the active ingredient in said transdermal therapeutic system applied to said second skin location is follicle-stimulating hormone and said method further comprises buffering the active ingredient layer of the second transdermal therapeutic system to a pH of approximately 7.

10. The method as claimed in claim 1 , wherein the follicle-stimulating hormone is follitropin.

11. The method as claimed in claim 1 , wherein the follicle-stimulating hormone is in the form of a pharmaceutically acceptable salt.

12. The method as claimed in claim 1 , wherein the GnRH agonist is selected from leuprolide, buserelin, nafarelin, histrelin, goserelin, deslorelin or triptorelin.

13. The method as claimed in claim 12 , wherein the GnRH agonist is triptorelin.

14. The method as claimed in claim 1 , wherein said prolonged time period is at least 12 hours.

15. The method as claimed in claim 1 , wherein said prolonged time period is 24 to 48 hours.

16. The method as claimed in claim 1 , wherein said steps of ablatively treating comprises forming microchannels that do not extend any deeper than down to the skin's dermis.

17. The method as claimed in claim 1 , wherein said method further comprises marking the ablatively treated skin with color.

18. The method as claimed in claim 1 , wherein the active ingredient layer of either the first or second transdermal therapeutic system comprises at least one substance from the group of nonpolymeric auxiliaries, buffers, stabilizers, and preservatives.

19. The method as claimed in claim 1 , wherein the active ingredient layer of either the first or second transdermal therapeutic system has been dried to a residual moisture content of 0.5 to 20%.

20. The method as claimed in claim 19 , wherein the active ingredient layer of either the first or second transdermal therapeutic system was applied as a solution onto a carrier substance and the solution comprises an aqueous solution and said method further comprises applying said transdermal therapeutic systems whose active ingredient layers comprising either GnRH agonist or follicle-stimulating hormone have been dried to a residual moisture content of below 5% of the total weight of said layer.

Assignees

• Lts Lohmann Therapie Systeme Ag

Inventors

• Horstmann Michael
• Hoffmann Gerd
• Wiedersberg Sandra

Classifications

• A61P5/06

  of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH · CPC title

• A61K9/7084 Primary

  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 title

• A61K38/24

  Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH] · CPC title

• A61K38/27

  Growth hormone [GH], i.e. somatotropin · CPC title