Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-11-05
2001-11-13
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S853000
Reexamination Certificate
active
06316483
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to aqueous nasal compositions comprising a medicament in an aqueous carrier containing a water soluble polymer selected from the group of polyvinylpyrrolidone and mixtures thereof. The combination of water soluble polymers provides unexpected properties which enhance medicinal efficacy and promotes organoleptic acceptance of the compositions
One of the major hindrances to effective systemic absorption of medicaments such as chlorpheniramine maleate in the nose is due to anatomical features of the epithelium within the nasal cavity. The constant beating of the nasal cilia causes the mucus film to continually move toward the nasopharynx. This action, in about 8 to 10 minutes, will remove the medicament from the nasal mucosa reducing the time for effective systemic absorption.
Certain medicaments are active topically and are not systemically absorbed, such as the topically active nasal decongestant oxymetazoline hydrochloride. This medicament is a vasoconstrictor that increases nasal airway volume by reducing blood flow to the nasal capillary bed. Oxymetazoline hydrochloride also reduces blood flow to the muco-secreting cells and as a result reduces nasal secretions. This reduction of natural moisture replacement in conjunction with moisture vaporization due to increased air flow volume promotes drying of the nasal cavity. Loss of this protective mucosal film may result in an increased occurrence in nasal sensitivity and associated burning and stinging.
It is known that when a combination of medicaments, such as chlorpheniramine maleate and oxymetazoline hydrochloride are incorporated into typical nasal spray formulations the occurrence of nasal burning and stinging increases.
Nasal drying and the associated stinging within the nasal cavity is one of the most common complaints of patients and consumers that use nasal spray products. Other common nasal product negative attributes include odor, taste and the tendency of the product to run out of the nose.
We have surprisingly discovered that incorporation of a combination of water soluble polymers selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol and mixtures thereof into nasal spray compositions provide enhanced medicinal efficacy and promotes organoleptic acceptance of the compositions.
It is an object of the present invention to provide nasal spray compositions exhibiting increased nasal retention of medicaments in the nasal cavity for enhanced topical or systemic activity.
Another object of the present invention is to provide nasal spray compositions exhibiting reduced post nasal drip.
It is a further object of the present invention to provide nasal spray compositions exhibiting increased moisturization in the nasal cavity.
A further object of the present invention is to provide nasal spray compositions which reduce the potential of medicament induced stinging, burning, overdrying or irritation.
SUMMARY OF INVENTION
The present invention provides aqueous nasal spray compositions comprising a medicament and an aqueous carrier containing a water soluble polymer selected from the group consisting of polyvinylpyrrolidone and mixtures thereof.
The present invention provides aqueous nasal spray compositions comprising an effective amount of a medicament in an aqueous carrier comprising:
0 0.50 to 15.00% by weight/volume of a water soluble polymer selected from the group consisting of polyvinylpyrrolidone and mixtures thereof;
0.00 to 15.00% by weight/volume of polyethylene glycol;
0.00 to 10.00% by weight/volume of a moisturizing agent or mixtures of moisturizing agents;
0.00 to 10.00% by weight/volume of an antioxidant;
0.001 to 0.10% by weight/volume of an antimicrobial preservative;
0.00 to 5.00% by weight/volume of an aromatic alcohol;
a sufficient amount of a pharmaceutically acceptable buffer to maintain the pH of the composition within the range of about 4.0 to 8.0 and
QS water.
The present invention further provides a method of treating nasal conditions by administering to a nasal passage of a patient an aqueous nasal spray composition of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
The aqueous nasal spray compositions of the present invention comprise a medicament in an aqueous carrier containing a water soluble polymer selected from the group consisting of polyvinylpyrrolidone and mixtures thereof.
Compositions of the present invention contain a therapeutically effective amount of at least one pharmaceutically acceptable medicament. The medicament drug may be selected from a wide range of therapeutic agents and mixtures of therapeutic agents. Illustrative categories and specific examples include. analgesics, such as ibuprofen and ketoprofen; antiasmatics, such as theophylline; antitussives, such as noscapine and chlophedinol hydrochloride; antihistamines, such as chlorpheniramine maleate, loratadine, azatadine; antinauseant, such as dimenhydrinate; decongestants, such as oxymetazoline hydrochloride; various alkaloids, such as codeine sulfate and morphine; stimulants, such as nicotine; mucolytics, such as acetylcysteine and bromhexine.
The preferred medicaments, alone or in combination, include chlorpheniramine maleate and oxymetazoline hydrochloride.
The amount of oxymetazoline hydrochloride found sufficient to effect nasal decongestion is from about 0.001 to about 0.2% by wt/vol of the total composition. Ranges of 0.01 to 0.1% of the total composition are particularly suitable. Typically, 0.05% by wt/vol is preferred for adults and children above five years of age.
The amount of chlorpheniramine maleate found sufficient for intranasal antihistamine action is from about 0.001 to about 2.0% by wt/vol of the total composition. Ranges of 0.1 to 0.5% by wt/vol is most preferable.
Various gums and polymers have been evaluated to determine suitability of such materials as bioadhesives to extend the nasal muco-cilia clearance time of nasal spray formulations. Desired properties of a bioadhesive include solubility clarity and compatibility in a conventional nasal spray formulation. In addition, the nasal spray composition containing the bioadhesive material was evaluated to determine the concentration effect on spray pattern and resultant mist properties.
It has been found that polyvinylpyrrolidone, a linear polymer 1-vinyl-2-pyrrolidone, hereinafter designated PVP, extends muco-cilia clearance times of nasal spray composition Polyvinylpyrrolidone, also known as Povidone, is commercially available as a series of products having mean molecular weights ranging from about 10,000 to about 700,000. The various products are marketed according to average molecular weights designated K-values; e.g. GAF Corporation supplies PVP having the following K-values:
K-value
Average Molecular Weight
15
about 10,000
30
about 40,000
60
about 160,000
90
about 360,000
The nasal spray compositions of this invention contain various grades of polyvinylpyrrolidone, i.e. K-15, K-30, K-60 and K-90. The polyvinylpyrrolidone ingredient may be present as one specific grade or as a combination of two or more grades.
The most preferable polymers of polyvinylpyrrolidone for the compositions of this invention are PVP K-30 and PVP K-90.
The amount of polyvinylpyrrolidone present in the compositions of this invention is from about 0.50 to 15.00% by weight/volume of the total composition. Ranges of 0.50 to 2.5% by weight/volume of the total composition are particularly suitable and a range of 1.00 to 1.50% by weight/volume of the total composition being most preferable.
To evaluate the effect of polyvinylpyrrolidone on nasal muco-cilia clearance time, a modified procedure was employed as disclosed by E. Puchelle, et al., in Acta Otolarynogol, 91, 297-303. (1981). The procedure utilized a concentrated sodium saccharin solution as the indicator. A 100 mcl dose of water-soluble polymer test solution was sprayed into the nose. After spraying, a cotton swab saturated with saccharin solution was inserted into the nostril and wiped around the ostuim depositing the saccharin onto
Haslwanter Joseph A.
Rencher William F.
Lee William
Mann Arthur
McQueeney P. E.
Page Thurman K.
Schering Corporation
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