INHALATIVE AND INSTILLATIVE USE OF SEMIFLUORINATED ALKANES AS AN ACTIVE SUBSTANCE CARRIER IN THE INTRAPULMONARY AREA

• US 20100008996A1
• Filed: 07/15/2009
• Published: 01/14/2010
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Novaliq GmbH
• Original Assignee: Novaliq GmbH
• Inventors: Meinert, Hasso
• Granted Patent: US 8,986,738 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/07 Retinol compounds, e.g. vitamin A retinoic acids A61K31/203
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A medical aid for the direct transport of at least one drug into lung regions of a patient, wherein provided as the carrier for at least one active substance is at least one semifluorinated alkane in which the at least one active substance is purely physically dissolved in a homogeneous phase.

Claims

1. A medical aid for the direct transport of at least one drug into lung regions of a patient, comprising a carrier for at least one active substance, wherein the carrier is at least one semifluorinated alkane in which the at least one active substance is purely physically dissolved in a homogeneous phase.

2. An aid according to claim 1, wherein at least one active substance is dissolved in colloidally- to molecularly-disperse fashion in the semifluorinated alkane.

3. An aid according to claim 1, wherein the medical aid is utilized in an application of active substances which is difficult or impossible in a conventional fashion, orally or by injection.

4. An aid according to claim 1, wherein the active substance is dissolved in the semifluorinated alkane at a concentration at which the solubility of the active substance is exceeded when the semifluorinated alkane is exhaled.

5. An aid according to claim 4, wherein the active substance is dissolved in the semifluorinated alkane in saturated or approximately saturated form.

6. An aid according to claim 1, wherein the solution comprising active substance and semifluorinated alkane occurs in the form of micelles.

7. An aid according to claim 1, wherein the medical aid is utilized in an application of the at least one active substance by inhalation, in the form of aerosols, or by instillation.

8. An aid according to claim 1, wherein for an aerosol, the solution of the at least one active substance in the semifluorinated alkane is suitable for being vaporized.

9. An aid according to claim 1, wherein for an aerosol, the solution of the at least one active substance in the semifluorinated alkane is suitable for being atomized by air or by means of oxygen-enriched air or by means of a gas mixture which maintains respiration.

10. An aid according to claim 1, wherein for an aerosol, the proportion of semifluorinated alkane, active substance and oxygen in the respiration gas is about 20% to 100%.

11. An aid according to claim 1, wherein for an aerosol, the semifluorinated alkane has a low boiling point in the region of human body temperature or room temperature or therebelow and forms both the solvent for the at least one active substance and also a system-specific propel lent.

12. An aid according to claim 1, wherein to deposit the at least one active substance on the alveolar membrane the semifluorinated alkane at body temperature is of a vapor pressure which causes a successive exhalation and the at least one active substance remains deposited on the alveolar membrane.

13. An aid according to claim 1, wherein the medical aid is adapted for instillative application for active substance transport into atelectactic lung regions.

14. An aid according to claim 1, wherein the medical aid is adapted for partial or total liquid ventilation.

15. An aid according to claim 1, wherein the particle size of the active substance is 100 nm to 1.0 nm.

16. An aid according to claim 1, wherein the medical aid is utilized to remove harmful substances on the lung surface.

17. An aid according to claim 1, wherein the medical aid is utilized to penetrate into lung emphysema regions.

18. An aid according to claim 1, wherein the medical aid is utilized for mucovicidosis therapy.

19. An aid according to claim 1, wherein the at least one active substance has a molecule structure of low outwardly acting polarity.

20. An aid according to claim 1, wherein at least one active substance is selected from the group of mucus-loosening and anti-spasmodic, bronchial-enlarging, surface-active, inflammation-inhibiting or anti-ischaemic substances.

21. An aid according to claim 1, wherein the at least one active substance for inhalative or instillative application with deposit action on the alveolar membrane is selected from the group consisting of:

cytostatic agents, virostatic agents, bacterostatic agents, anti-asthmatic agents, antihistamine agents, inflammation-inhibiting, bronchial-enlarging and circulation-promoting drugs, proteins, in particular growth factors, peptides and vitamins.

22. An aid according to claim 1, wherein the active substance for a passage of the alveolar membrane and transport into the bloodstream has a particle size of 1.0 nm to 0.1 nm.

23. An aid according to claim 22, wherein the active substance particles are present in finely divided form in the semifluorinated alkane.

24. An aid according to claim 22, wherein the active substance particles are finely distributed in the semifluorinated alkane by physical homogenisation.

25. An aid according to claim 22, wherein the active substance particles are encased with a monolayer solvate case.

26. An aid according to claim 22, wherein to prevent coagulation or Ostwald ripening the RF-groups of the solvate molecules are directed outwardly.

27. An aid according to claim 1, wherein the active substance is pre-produced in the nano range or is produced ab initio in the semifluorinated alkane.

28. An aid according to claim 22, wherein the at least one active substance is adapted for passage through the alveolar membrane and absorption in the bloodstream, for a time-diffusion-controlled process.

29. An aid according to claim 22, wherein the medical aid is utilized for an intrapulmonary transport of the at least one active substance into the bloodstream, the use of which is linked to the risk of subcutaneous or intramuscular or intravenous infection.

30. An aid according to claim 22, wherein the medical aid is utilized for an intrapulmonary transport into the bloodstream of at least one active substance for the treatment of chronic diseases, which for a recidivising medication, is orally not available, or orally poorly effective, or orally leads to severe side-effects.

31. An aid according to claim 22, wherein the medical aid is utilized for an intrapulmonary transport into the bloodstream of at least one active substance which suffers breakdown in the gastrointestinal path.

32. An aid according to claim 1, comprising a w/o- or o/w-emulsion as the active substance carrier.

33. An aid according to claim 32 wherein the at least one active substance is used in water-soluble form.

34. An air according to claim 32, wherein the active substance is used in the form of its hydrochloride, phosphate or alkali salt.

35. An aid according to claim 1, wherein the active substance is dissolved in its base form in the semifluorinated alkane.

36. The process of using at least one semifluorinated alkane in diblock form, for the production of a medical aid according to claim 1.