Pharmaceutical composition for application to mucosa

• US 6,939,559 B1
• Filed: 04/21/1999
• Issued: 09/06/2005
• Est. Priority Date: 04/21/1998
• Status: Expired due to Term

• Current Assignee: Teijin Limited
• Original Assignee: Teijin Limited
• Inventors: Nishibe, Yoshihisa, Kawabe, Hiroyuki, Kinoshita, Wataru
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/446,276
• Time in Patent Office: 2,330 Days
• Field of Search: 424/434
• US Class Current: 424/434
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/186 Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 5/22 for decreasing, blocking or antagonising the activity of calcitonin
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

The present invention provides a pharmaceutical composition for application to the mucosa to be used in drug therapy comprising a water-insoluble and/or water-low soluble substance, a medicament, and an aqueous medium, and having an osmotic pressure of less than 290 mOsm. This composition is superior over conventional pharmaceutical compositions for application to the mucosa, due to efficient and high permeability to the blood at the mucosa. The present invention further provides a pharmaceutical composition for application to the mucosa comprising a hemostatic agent and a medicament. This composition is superior over conventional pharmaceutical compositions for application to the mucosa, due to permeability and retentivity at the mucosa.

Claims

1. An aqueous pharmaceutical composition for application to the mucosa, comprising one or more water-insoluble and/or low water soluble substance, and one or more medicament, and having an osmotic pressure of 72 mOsm or less.

4. The pharmaceutic composition for application to the mucosa according to claim 1 or 3, wherein said osmotic pressure is 60 mOsm or less.

5. The pharmaceutical composition for application to the mucosa according to claim 1 or 3, wherein said osmotic pressure is 30 mOsm or less.

6. The pharmaceutical composition for application to the mucosa according to claim 1 or 3, wherein said osmotic pressure is 10 mOsm or less.

7. The pharmaceutical composition for application to the mucosa according to claim 1 or 3, further comprising an osmotic pressure-controlling agent.

8. The pharmaceutical composition for application to the mucosa according to claim 7, wherein said osmotic pressure-controlling agent is a salt.

9. The pharmaceutical composition for application to the mucosa according to claim 7, wherein said osmotic pressure-controlling agent is sodium chloride.

10. The pharmaceutical composition for application to the mucosa according to claim 7, wherein said osmotic pressure-controlling agent is a water-soluble sugar.

11. The pharmaceutical composition for application to the mucosa according to claim 7, wherein said osmotic pressure-controlling agent is glucose.

12. The pharmaceutical composition for application to the mucosa according o claim 1 or 3, wherein said water-insoluble and/or low water soluble substance is a cellulose.

13. The pharmaceutical composition for application to the mucosa according to claim 12, wherein said cellulose is crystalline cellulose.

14. The pharmaceutical composition for application to the mucosa according to claim 1 or 3, wherein said one or more water-insoluble and/or low water soluble substance is present as solid particles in an aqueous medium.

15. The pharmaceutical composition for application to the mucosa according to claim 1 or 3, wherein said one or more water-insoluble and/or low water soluble substance is dispersed as solid particles in an aqueous medium.

16. The pharmaceutical composition for application to the mucosa according to claim 1 or 3, further comprising a water-soluble polymer substance.

17. The pharmaceutical composition for application to the mucosa according to claim 16, wherein said water-soluble polymer is one or more selected from the group consisting of alginic acid, polyethylene glycol, glycerin, polyoxyethylene polyoxypropylene glycol, propylene glycol, pectin, low methoxyl pectin, guar gum, gum arabic, carrageenan, methyl cellulose, carboxymethyl cellulose sodium, xanthan gum, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose.

18. The pharmaceutical composition for application to the mucosa according to claim 16, wherein said water-soluble polymer is carboxymethyl cellulose sodium.

19. The pharmaceutical composition for application to the mucosa according to claim 16, wherein said water-soluble polymer is xanthan gum.

20. The pharmaceutical composition for application to the mucosa according to claim 16, wherein said water-soluble polymer is hydroxypropyl methyl cellulose.

21. The pharmaceutical composition for application to the mucosa according to claim 16, wherein the combination of said water-insoluble substance and water-soluble polymer is crystalline cellulose carmellose sodium.

22. The pharmaceutical composition for application to the mucosa according to claim 1 or 3, further comprising a surfactant.

23. The pharmaceutical composition for application to the mucosa according to claim 22, wherein said surfactant is polysorbate 80.

24. The pharmaceutical composition for application to the mucosa according to any of claim 1 or 3, wherein said medicament is a water-soluble medicament.

25. The pharmaceutical composition for application to the mucosa according to any of claim 1 or 3, wherein said medicament is a liposoluble medicament.

26. The pharmaceutical composition for application to the mucosa according to claim 1 or 3, wherein said mucosa is nasal mucosa.

2. A pharmaceutical composition for application to the mucosa, comprising one or more hemostatic agent and one or more medicament.

3. An aqueous pharmaceutical composition for application to the mucosa, comprising one or more hemostatic agent, one or more water-insoluble and/or low water soluble substance, and one or more medicament, and having an osmotic pressure of 72 mOsm or less.

27. The pharmaceutical composition for application to the mucosa according to claim 3, wherein said hemostatic agent is one or more selected from the group consisting of tranexamic acid, epsilon aminocaproic acid, carbazochrome, carbazochrome sulfonate, carbazochrome sodium sulfonate, phytonadione, etamsylate, monoethanol amine oleate, thrombin, hemocoaglase, and adrenochrome monoaminoguanidine mesilate.

28. The pharmaceutical composition for application to the mucosa according to claim 3, wherein the agent other than said hemostatic agent is one or more selected from the group consisting of an antiallergic agent, an antihistamic agent, an anticholinergic agent, a steroid, a vaccine, and a substance for gene therapy, and the mucosa is nasal mucosa.

29. The pharmaceutical composition for application to nasal mucosa according to claim 28, wherein the agent other than said hemostatic agent is a steroid.