LAG TIME REDUCTION/ICE SPRAY

Abstract

The present invention relates to a kit, comprising at least one cold spray and at least one dosage form for transdermally administering at least one pharmaceutically active ingredient, to said kit for use in the treatment of a patient, to the use of a cold spray in order to shorten the resorption delay time in the application of a dosage form for transdermally administering at least one pharmaceutically active ingredient, and to a method for treating a patient.

Claims

1. A kit, comprising at least one cold spray and at least one dosage form for transdermally administering at least one pharmaceutically active ingredient.

2. The kit according to claim 1, characterised in that the at least one dosage form comprises a transdermal therapeutic system, a gel, a lotion, an ointment, a cream and/or a microneedle system.

3. The kit according to claim 1, characterised in that the at least one pharmaceutically active ingredient is selected from the group consisting of hypnotics, sedatives, antiepileptics, analeptics, psychoneurotropic drugs, neuromuscular blockers, antispasmodics, antihistamines, antiallergics, cardiotonics, antiarrhythmics, diuretics, hypotensives, vasopressors, antitussives, expectorants, analgesics, thyroid hormones, sexual hormones, glucocorticoid hormones, antidiabetics, antitumour drugs, antibiotics, chemotherapeutics, narcotics, anti-Parkinson drugs, anti-Alzheimer drugs and/or triptans.

4. The kit according to claim 1, characterised in that the cold spray comprises a liquid gas filled in a spray can.

5. The kit according to claim 4, characterised in that the liquid gas comprises propane, butane, pentane, tetrafluoroethane, dimethyl ether and/or chloroethane.

6. The kit according to claim 1 for use in the treatment of a patient.

7. A method for reducing the resorption delay time in the application of a dosage form comprising transdermally administering at least one pharmaceutically active ingredient in a cold spray.

8. The method according to claim 7, characterised in that the dosage form comprises a transdermal therapeutic system, a gel, a lotion, a suspension ointment and/or a microneedle system.

9. The method according to claim 7, characterised in that the at least one pharmaceutically active ingredient is selected from the group consisting of hypnotics, sedatives, antiepileptics, analeptics, psychoneurotropic drugs, neuromuscular blockers, antispasmodics, antihistamines, antiallergics, cardiotonics, antiarrhythmics, diuretics, hypotensives, vasopressors, antitussives, expectorants, analgesics, thyroid hormones, sexual hormones, glucocorticoid hormones, antidiabetics, antitumour drugs, antibiotics, chemotherapeutics, narcotics, anti-Parkinson drugs, anti-Alzheimer drugs and/or triptans.

10. The method according to claim 7, characterised in that the cold spray comprises a liquid gas filled in a spray can.

11. The method according to claim 10, characterised in that the liquid gas comprises propane, butane, pentane, tetrafluoroethane, dimethyl ether and/or chloroethane.

12. A method for treating a patient, comprising the steps of cooling at least one area of the patient's skin and applying a dosage form for transdermally administering at least one pharmaceutically active ingredient to the cooled area of the skin.

13. The method according to claim 12, characterised in that the skin is cooled by being treated with a cold spray.

14. The method according to claim 13, characterised in that the treatment with a cold spray lasts for between 3 sec and 20 sec.

15. The method according to claim 12, characterised in that the dosage form comprises a transdermal therapeutic system, a gel, a lotion, a suspension ointment and/or a microneedle system.

Description

FIGURES

[0075] FIG. 1 shows the results of the measurement of the in vitro human skin permeation during the application of test samples of the transdermal therapeutic system Neupro® (10 cm.sup.2 TTS from UCB Pharma GmbH, Germany, with a delivery rate of 2 mg/24 h and a content of 4.5 mg active ingredient, pharmaceutical registration number 10393704) for the administration of rotigotine with and without a prior skin treatment with a cold spray. The resorption delay time was reduced by a factor of 1.4.

[0076] FIG. 2 shows the results of the measurement of the in vitro human skin permeation during the application of test samples of the transdermal therapeutic system Scopoderm® (2.5 cm.sup.2 TTS from Novartis Consumer Health GmbH, Germany, with a delivery rate of 1.0 mg/72 h and a content of 1.54 mg active ingredient, pharmaceutical registration number 00107146) for the administration of scopolamine with and without a prior skin treatment with a cold spray. The resorption delay time was reduced by a factor of 2.0.

[0077] FIG. 3 shows the results of the measurement of in vitro human skin permeation during the application of the transdermal therapeutic system Voltaren Tape 30 Dojin® (140 cm.sup.2 patch from Iyaku-Kako Co Ltd, Japan, with a content of 30 mg active ingredient; a delivery rate cannot be given for this system as it is a topical system. As the product is only approved and distributed in the Asian region, no pharmaceutical registration number can be given). for the administration of Diclofenac sodium with and without a prior skin treatment with a cold spray. The resorption delay time was reduced by a factor of 2.0.

[0078] The invention will be described in greater detail hereinafter on the basis of non-limiting examples.

EXAMPLE 1

[0079] The reduction of the skin barrier was determined by measuring the TEWL (transepidermal water loss). The higher the TEWL value, the more the skin barrier is reduced.

[0080] For this purpose, TEWL values were determined using an AquaFlux200 measuring probe from Biox, London, UK. The sample in each case was 800 μm dermatomised human abdominal skin from a 71-year-old female donor who was treated for a certain time with the cold spray Servisol® Freeze IT 20 (Servisol Bridgewater, Somerset, UK) from a distance of about 15 cm. The measurement results before and after cold spray treatment are summarised in Table 1.

TABLE-US-00001 TABLE 1 TEWL TEWL before cold after cold TEWL TEWL after Test Treatment treatment treatment increase 30 min no. type [g/m.sup.2 × h] [g/m.sup.2 × h] [g/m.sup.2 × h] [g/m.sup.2 × h] 1 5 sec cold 15.63 46.90 31.28 14.71 spray 2 5 sec cold 14.91 52.29 37.38 18.74 spray 3 10 sec cold 13.54 56.84 43.30 16.42 spray 4 10 sec cold 14.44 47.73 32.99 13.15 spray

[0081] According to the German Society for Dermatopharmacy, an intact skin barrier is characterised by a TEWL range of 10 to 24 g/m.sup.2×h. The values in the sixth column show that the process is reversible and does not lead to skin damage.

EXAMPLE 2

[0082] The in vitro human skin permeation of three commercially available transdermal therapeutic systems without and with prior cold treatment was determined. For this purpose, the skin samples were treated completely over their surface for 10 sec from a distance of about 15 cm with a cold spray (Servisol® Freeze IT 20). After about 10 sec (an ice film is formed, which should preferably have disappeared again first), the corresponding transdermal therapeutic system was applied to the treated area of the skin and the permeation profile (cumulatively permeated amount as a function of time) was measured using a Franz cell.

[0083] The donor compartment of the Franz cell contained the transdermal therapeutic system. The acceptor compartment of the Franz cell was filled with buffer or other solutions. By regularly taking samples from the acceptor compartment, the permeation of a substance through the skin could be followed over the selected time period. The use of the Franz cell as a diffusion model is especially suitable for predicting the transport of drugs through human skin (=permeation), which corresponds to systemic availability.

[0084] Here, circular die-cuts, measuring 1.17 cm.sup.2, of the transdermal therapeutic systems were glued onto the epidermal side (skin surface) of 800 μm dermatomised circular skin pieces with a diameter of 25 mm, once after and once without (reference) skin pre-treatment. An aqueous isotonic phosphate buffer pH=5.5 plus 0.1% sodium azide as preservative with a filling volume of 10 ml was used as acceptor medium. The permeation was measured at a temperature of 32° C. and the values were determined after 1, 2, 3 and 4 hours for Neupro®, after 1.5, 2, 3, 4, 6 and 8 hours for Scopoderm® and after 1, 2, 3, 6 and 8 hours for Dojin®. The respective measurement results with the transdermal therapeutic systems Neupro®, Scopoderm® and Dojin® can be seen in FIGS. 1, 2 and 3.