Pharmaceutical compositions comprising flavonoids and menthol

• US 20060148726A1
• Filed: 09/19/2003
• Published: 07/06/2006
• Est. Priority Date: 10/24/2002
• Status: Active Grant

• Current Assignee: Immunpharm A/S
• Original Assignee: ImmuPharm A/S
• Inventors: Berg, Kurt Frimann
• Granted Patent: US 7,585,890 B2
• Time in Patent Office: Days
• US Class Current: 514/27
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/315 Zinc compounds
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses

Abstract

The present invention relates to use of certain antiviral fragrances for reduction of viruses, in particular vira causing common cold. In one embodiment, the invention relates to pharmaceutical compositions comprising an antiviral fragrance, preferably menthol. Said compositions preferably also comprise one or more flavonoids. The invention also relates to treatment of common cold using said compositions.

Claims

1. A pharmaceutical composition comprising

i) one or more purified flavonoids;

and

ii) purified menthol; and

iii) pharmaceutically acceptable exipients.

2. The pharmaceutical composition according to claim 1, wherein said composition essentially consists of

i) one or more purified flavonoids;

and

ii) purified menthol; and

iii) pharmaceutically acceptable exipients, wherein said exipients are not therapeutically active.

3. The pharmaceutical composition according to claim 1, wherein said composition also comprises a pharmaceutically acceptable metal complex and/or metal salt.

4. The pharmaceutical composition according to claim 3, wherein said composition essentially consists of

i) one or more purified flavonoids;

and

ii) purified menthol; and

iii) one or more metal complexes and/or metal salts; and

iv) pharmaceutically acceptable expients, wherein said expients are not therapeutically active.

5. The pharmaceutical composition according to claims 3, wherein said metal is zinc.

6. The pharmaceutical composition according to claims 3, wherein the metal is zinc selected from the group consisting of Zn²⁺ aminochelates , Zn²⁺ amino acid chelates, Zn(acetate)₂, Zn²⁺ DL-methionine, Zn²⁺ L-methionine, ZnGluconate and PolaPreZinc®

.

7. The pharmaceutical composition according to claim 1, wherein said composition is useful for oral and/or nasal administration.

8. The pharmaceutical composition according to claim 1, wherein said composition is selected from the group consisting of lozenges, troches, capsules, syrups, tablets, lollipops, solutions, dispersions, suspensions, powders, micropheres, chewing tablets, chewing gums, sprays, droppers, pipettes and pills.

9. The pharmaceutical composition according to claim 1, wherein said composition is a slow-release composition.

10. The pharmaceutical composition according to claim 1, wherein said composition is lozenges.

11. The pharmaceutical composition according to claim 1, wherein said composition is essentially free of crude plant extracts.

12. The pharmaceutical composition according to claim 1, wherein said composition is essentially free of other terpenes than menthol.

13. The pharmaceutical composition according to claim 1, wherein said composition is essentially free of one or more selected from the group consisting of menthone, menthyl acetate, limonene and neomenthol.

14. The pharmaceutical composition according to claim 1, wherein one or more flavonoids are chelating a metal.

15. The pharmaceutical composition according to claim 1, wherein the metal is Zn²⁺.

16. The pharmaceutical composition according to claim 1, wherein the flavonoid is selected from the group consisting of flavonoids of the general formula:

17. The pharmaceutical composition according to claim 1, wherein the flavonoid is selected from the group consisting of troxerutin, venoruton, hesperitin, naringenin, nobiletin, tangeritin, baicalein, galangin, genistein, quercetin, apigenin, kaempferol, fisetin, rutin, luteolin, chrysin, taxifolin, eriodyctol, catecithin, epicatechin gallate, epigallocatechin gallate, flavone, sideritoflavone, hypolaetin-8-O-Gl, oroxindin, 3-hydroxyflavone, morin, quercetagetin-7-O-Gl, tambuletin, gossypin, hipifolin, naringin, leucocyanidol, amentoflavone and derivatives thereof and mixtures thereof.

18. The pharmaceutical composition according to claim 1, wherein said flavonoid is not a naturally occurring flavonoid.

19. The pharmaceutical composition according to claim 1, wherein said flavonoid is a rutoside.

20. The pharmaceutical composition according to claim 1, wherein at least one flavonoid is a rutoside aglycone.

21. The pharmaceutical composition according to claim 1, wherein said flavonoid is a hydroxyethylrutoside.

22. The pharmaceutical composition according to claim 1, wherein at least one flavonoid is a hydroxyethythyrutoside aglycone.

23. The pharmaceutical composition according to claim 1, wherein said composition comprises a mixture of hydroxyethylrutosides.

24. The pharmaceutical composition according to claim 1, wherein said composition comprises a mixture of mono-, di-, tri- and tetrahydroxyethylrutosides.

25. The pharmaceutical composition according to claim 1, wherein at least one flavonoid is troxerutin.

26. The pharmaceutical composition according to claim 1, where at least one flavonoid is troxerutin aglycone.

27. The pharmaceutical composition according to claim 1, wherein the flavonoid is veneruton.

58. A method of treatment of a clinical condition or symptoms of a clinical condition in an individual in need thereof, comprising administering to said individual the pharmaceutical composition according to claims 1.

59. The method according to claim 58, wherein said clinical condition is a condition relating to common cold.

60. The method according to claim 58, wherein the clinical condition is common cold of the upper and/or lower respiratory tract and/or eyes.

61. The method according to claim 59, wherein the conditions relating to common cold are viral infections of the upper and/or lower respiratory tract and/or eyes.

62. The method according to claim 59, wherein the conditions relating to common cold are bacterial infections of the upper and/or lower respiratory tract and/or eyes.

63. The method according to claim 59, wherein the conditions relating to common cold are allergic conditions of the upper and/or lower respiratory tract and/or eyes.

64. The method according to claim 59, wherein the conditions relating to common cold are characterized by one or more symptoms of the group comprising coughing, sneezing, muscle pain, sore throat, irritated throat, hoarseness, headache, malaise, chilliness, fever, nasal discharge, nasal obstruction, pain relating to the sinuses, rhinitis, swelling of mucosal membranes, pharyngitis, asthma, and bronchitis.

65. The method according to claim 59, wherein the condition relating to common cold is a viral infection caused by or associated with one or more viruses selected from the group consisting of adenoviruses, parvoviruses, picornaviruses, reoviruses, orthomyxoviruses, paramyxoviruses, arenaviruses, caliciviruses, coronaviruses, orthomyxoviruses, rhinovirus, influenza virus, including influenza virus type A and B, echovirus and coxsackie virus.

66. The method according to claim 59, wherein the condition relating to common cold is a viral infection caused by or associated with one or more viruses selected from the group consisting of coronaviruses and rhinoviruses.

67. The method according to claim 59, wherein the condition relating to common cold is a bacterial infection caused by or associated with one or more bacteria selected from the group consisting of Streptococcus pheumoniae, Streptococcus Haemolyticae, Haemophilus influenxae, and Moraxella catarrhalis.

68. The method according to claim 59, wherein the condition relating to common cold is an allergic condition selected from the group consisting of rhinitis, acute and chronic bronchitis and hay fewer.

69. The method according to claim 59, wherein the condition related to common cold is an allergic condition characterised by one or more symptoms selected from the group consisting of nasal discharge, nasal congestion, sneezing, cough, swelling of mucosal membranes and rhinitis.

70. The method according to claim 58, wherein the administration is to the mucosal membrane of the upper and/or lower respiratory tract and/or of the eyes.

71. The method according to claim 58, wherein the administration is topical to the mucosal membrane of the oral cavity.

81. The method according to claim 58, wherein said flavonoid is a hydroxyethylrutoside.

82. The method according to claim 58, wherein at least one flavonoid is troxerutin.

83. The method according to claim 58, wherein said composition also comprises a pharmaceutically acceptable metal complex and/or metal salt.

28-57. -57. (canceled)

72-73. -73. (canceled)

74. A method of reducing the amount of virus in a composition, comprising incubating said composition comprising virus with menthol.

75. The method according to claim 74, wherein said virus is rhinovirus.

76. A method of reducing the amount of virus in an individual infection with said virus, comprising administering to said individual a pharmaceutical composition comprising menthol, thereby reducing the amount of said virus in said individual.

77. The method according to claim 76, wherein said virus is rhinovirus.

78. The method according to claim 76, wherein the method further comprises administering at least one flavonoid to said individual.

79-80. -80. (canceled)