Inhalative and instillative use of semifluorinated alkanes as an active substance carrier in the intrapulmonary area

• US 8,986,738 B2
• Filed: 03/31/2009
• Issued: 03/24/2015
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Novaliq GmbH
• Original Assignee: Novaliq GmbH
• Inventors: Meinert, Hasso
• Primary Examiner(s): Haghighatian, Mina
• Application Number:
  US12/415,482
• Publication Number:
  US 20100008996A1
• Time in Patent Office: 2,184 Days
• Field of Search: 424/489, 424/45, 514/1.1, 514/759, 514/772
• 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 composition configured for administering by direct transport of at least one drug directly into lung regions of a patient during inhalation, comprising:

a carrier for at least one active substance, wherein the carrier is at least one semifluorinated alkane of the type RFRH, wherein RF is a straight chain or branched perfluoro alkyl group and RH is a straight chain or branched saturated hydrocarbon group, and wherein the composition comprises a solution at room temperature and wherein at least part of the carrier vaporizes at temperatures in the lung regions of a patient;

wherein the length of each RF and RH segment is 2 to 20 carbon atoms, the at least one active substance being dispersed in the carrier as a colloid or molecular dispersion with a particle size of less than 100 nm at a concentration at which the active substance is configured to remain deposited when the semifluorinated alkane is exhaled; and

wherein the at least one active substance is selected from the group consisting of mucolytic and antispasmodic, bronchial-enlarging, surface-active, antiinflammatory and antiischaemic substances, or wherein the at least one active substance is selected from the group consisting of the cytostatic agents, antiviral agents, bacteriostatic agents, antiasthmatic agents, antihistamines, antiinflammatory, bronchial-enlarging, circulation-enhancing medicaments, proteins, growth factors, peptides, and vitamins.

2. The composition according to claim 1, wherein the composition comprising the at least one active substance and semifluorinated alkane occurs in the form of micelles.

3. The composition according to claim 1, wherein the composition comprises an aerosol, the composition of the at least one active substance in the semifluorinated alkane is atomizable by air or by oxygen-enriched air or by a gas mixture which maintains respiration.

4. The composition according to claim 3, wherein the composition is in the form of an aerosol, and comprises a semifluorinated alkane, active substance and oxygen, wherein the composition forms about 20% to 100% of respiration gas.

5. The composition according to claim 1, wherein at least one active substance is depositable on an alveolar membrane, the composition comprising a semifluorinated alkane and the at least one active substance depositable on the alveolar membrane, wherein the semifluorinated alkane at body temperature is of a vapor pressure which causes the at least one active substance to remain deposited on the alveolar membrane during a successive inhalation.

6. The composition according to claim 1, wherein the composition is adapted for instillative application for active substance transport into a region of the lung that is atelectactic.

7. The composition according to claim 1, wherein the medical composition is penetrable into lung regions affected by emphysema.

8. The composition according to claim 1, wherein the medical composition comprises a mucoviscidosis therapy composition.

9. The composition according to claim 1, wherein at least one active substance is selected from the group consisting of expectorant, anti-spasmodic, bronchial-enlarging, surface-active, inflammation-inhibiting and anti-ischaemic substances.

10. The composition according to claim 1, wherein the active substance is selected from the group consisting of:

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

11. The composition according to claim 1, wherein the medical composition comprises 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.

12. The composition according to claim 1, wherein the medical composition comprises 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.

13. The composition according to claim 1, wherein the medical composition comprises an intrapulmonary transport into the bloodstream of at least one active substance which suffers breakdown in the gastrointestinal path.

14. The composition according to claim 10, wherein the protein comprises a growth factor.

16. The composition according to claim 1, wherein the active substance is dispersed in saturated form in the semifluorinated alkane.

17. The composition according to claim 1, wherein the active substance has a particle size in the range from 100 to 1 nm.

18. The composition according to claim 1, wherein the active substance is an organic substance.

19. The composition according to claim 1, wherein the active substance is dispersed in saturated or partially saturated form in the semifluorinated alkane.

15. A method of depositing an active substance on a lung, comprising:

selecting at least one active substance from the group consisting of mucolytic and antispasmodic, bronchial-enlarging, surface-active, anti-inflammatory and anti-ischaemic substances, or selecting the at least one active substance from the group consisting of the cytostatic agents, antiviral agents, bacteriostatic agents, antiasthmatic agents, antihistamines, anti-inflammatory, bronchial-enlarging, circulation-enhancing medicaments, proteins, growth factors, peptides, and vitamins;

dispersing the at least one active substance in a carrier including a semifluorinated alkane, the composition comprising a colloid or molecular dispersion at room temperature with a particle size of less than 100 nm and at a concentration at which the active substance remains deposited on the surface of the lung and at least part of the carrier vaporizes at temperatures in the lung regions of a patient;

administering the composition comprising the dispersed active substance and the semifluorinated alkane being of the type RFRH, wherein RF is a straight chain or branched perfluoro alkyl group and RH is a straight chain or branched saturated hydrocarbon group with the length of each RF and RH segment being 2 to 20 carbon atoms, by directly transporting the composition to a surface of the lung during inhalation, and

depositing the active substance on the surface of the lung when the semifluorinated alkane is exhaled.