Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
1999-09-21
2001-04-03
Cook, Rebecca (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S547000, C514S556000, C514S557000, C514S560000, C514S566000, C514S568000, C514S912000, C424S659000
Reexamination Certificate
active
06211238
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates generally to the preservation of pharmaceutical compositions. In particular, the present invention relates to the use of certain anionic surfactants in combination with an antifungal acid and a chelating agent as a preservative system for topically administrable pharmaceutical compositions.
Multi-dose pharmaceutical products, particularly those intended for topical administration to the eyes, nose or ears, often contain or are required to contain a preservative. Such products are sterilized when manufactured, but contain preservatives to prevent or inhibit microbial growth in the event they are contaminated during use. The most common preservatives for topical, multi-dose ophthalmic products are quaternary ammonium preservatives, such as benzalkonium chloride and polyquaternium-1. Other known preservatives for topical, multi-dose ophthalmic products are chlorobutanol; chlorhexidine; parabens; and thimerosal (though thimerosal is not as common as it used to be, due to regulatory and environmental concerns related to the fact it contains mercury).
In some instances, preservatives alone are insufficient to meet regulatory standards for preservative efficacy. In such cases, preservative aids or adjuncts are used. Examples of preservative enhancing additives include the chelating agent EDTA (edetate disodium) and the antifungal agent boric acid. Additional examples of preservative enhancing additives include certain sarcosinate and lactylate surfactants.
U.S. Pat. No. 5,520,920 (Castillo, et al.) discloses the use of certain modified sarcosinates and lactylates to enhance antimicrobial effectiveness of ophthalmic compositions, particularly in the case where cationic preservatives otherwise bind to anionic polyelectrolytes. Representative modified sarcosinates include those sold under the Hamposyl® trade name, such as lauroyl sarcosine (Hamposyl® L), oleoyl sarcosine (Hamposyl® O), myristoyl sarcosine (Hamposyl® M), cocoyl sarcosine (Hamposyl® C), stearoyl sarcosine (Hamposyl® S), and pelargodoyl sarcosine (Hamposyl® P). Representative lactylates include sodium capryl lactylate (Pationic® 122A).
Anionic amino acid based surfactants other than the Hamposyl® surfactants are known and include, for example, those surfactants sold under the Amilite™ and Amisoft™ trade names (Ajinomoto Co., Inc., Tokyo, Japan). According to its product brochure, one such surfactant, Amilite™ GCK-12, is used as a detergent, a foaming agent, an emulsifier, a solubilizer and a dispersing agent. Examples of applications of Amilite™ GCK-12 include cosmetics and toiletries (hair shampoo and body wash), face wash (facial washing foam, facial washing creme, facial washing liquid and make-up remover), facial soap, toothpaste, bath soap, contact lens cleaners and household cleaners. Amisoft™ surfactants are described as gentle cleansers for the skin and hair. Major applications of Amisoft™ surfactants include facial and body cleansers, hair shampoos, syndet bars, body care and dermatological products.
Alternative preservative systems for topically administrable pharmaceutical compositions are desired, especially in those instances when conventional preservatives, such as benzalkonium chloride, are incompatible with other ingredients in the composition.
SUMMARY OF THE INVENTION
The present invention provides a preservative system for topically administrable pharmaceutical compositions. The preservative system consists essentially of i) at least one anionic surfactant of formula I or formula II below, ii) one or more pharmaceutically acceptable antifungal acids, and iii) one or more pharmaceutically acceptable chelating agents.
wherein: R=C
8
-C
24
saturated or unsaturated hydrocarbon;
X=H or CH
3
;
Y=H, (CH
2
)
4
NH
2
or (CH
2
)
3
NHC(NH
2
)═N
+
H
2
; and
M
+
=H or a pharmaceutically acceptable salt.
wherein: R
1
=C
8
-C
24
saturated or unsaturated hydrocarbon; and
M
+
is as defined above.
According to the present invention, topically administrable pharmaceutical compositions are preserved without the need for a conventional preservative ingredient. Thus, the compositions of the present invention do not contain any preservatives selected from the group consisting of quaternary ammonium preservatives, such as benzalkonium chloride, benzalkonium bromide, and polyquaternium-1; chlorhexidine; chlorobutanol; cetylpyridinium chloride; parabens; and thimerosal.
The present invention also relates to a method of preserving a topically administrable pharmaceutical composition, wherein the method comprises adding the preservative system described above to such composition.
Among other factors, the present invention is based on the finding that topically administrable pharmaceutical compositions can be preserved using a preservative system consisting of one or more anionic surfactants of formula I or II, one or more pharmaceutically acceptable antifungal acids and one or more pharmaceutically acceptable chelating agents, without the need for a conventional preservative ingredient.
DETAILED DESCRIPTION OF THE INVENTION
Unless indicated otherwise, all amounts of composition ingredients expressed in percentage terms are expressed as weight/weight.
The anionic surfactants of the present invention can be made by known methods and, in some cases, are commercially available. For example, Amilite™ GCK-12 is commercially available from Ajinomoto Co., Inc. (Tokyo, Japan). Amilite™ GCK-12 is described by formula I above when R is selected to be cocoyl (derived from coconut oil); X is H; Y is H; and M
+
is K
+
(i.e., potassium cocoyl glycinate). Lauroyl sarcosine is available from W.R. Grace (Lexington, Mass.) as Hamposyl® L. Lauroyl sarcosine is described by formula I above when R is selected to be lauroyl; X is CH
3
; Y is H; and M
+
is H
+
. Pationic® 122A is available from RITA, Corp. (Woodstock, Ill.). Pationic® 122A is described by formula II above when R
1
is selected to be a C
9
saturated hydrocarbon and M
+
is Na
+
.
Preferred anionic fatty acid/amino acid surfactants of formula I include those where R is a C
12
-C
18
saturated or unsaturated hydrocarbon and M
+
is selected from the group consisting of H
+
; Na
+
; K
+
; and triethanolamine.
Preferred anionic surfactants of formula II include those where R
1
is a C
12
-C
18
saturated or unsaturated hydrocarbon and M
+
is selected from the group consisting of H
+
; Na
+
; K
+
; and triethanolamine.
In general, the amount of anionic amino acid/fatty acid surfactant of formula I in the compositions of the present invention is from about 0.001 to about 1%, preferably from about 0.01 to about 0.2%. The amount of anionic surfactant of formula II in the compositions of the present invention is from about 0.05 to about 1.5%, preferably about 0.1 to about 1%, and most preferably about 0.1 to about 0.5%. For topical ophthalmic preparations, the concentration of anionic surfactant (formula I or II) should not be so high that it causes severe discomfort.
The preservative systems of the present invention also contain one or more pharmaceutically acceptable antifungal acids selected from the group consisting of boric acid; benzoic acid; salicylic acid; sorbic acid; lactic acid; acetic acid; and pharmaceutically acceptable salts thereof. Boric acid is the most preferred antifungal acid. In general, the amount of antifungal acid present in the compositions of the present invention is from about 0.01 to about 1%, preferably about 0.1 to about 0.6%, and most preferably from about 0.3 to about 0.4%. The antifungal acid component can be added to pharmaceutical compositions in the form of a pharmaceutically acceptable salt.
In addition to the anionic surfactant(s) and antifungal acid(s), the preservative system contains one or more pharmaceutically acceptable chelating agents. Such chelating agents are selected from the group consisting of ethylene diamine tetraacetic acid (EDTA); ethylene glycol-b
Castillo Ernesto J.
Gerson Steven Howard
Han Wesley Wehsin
Alcon Laboratories Inc.
Cook Rebecca
Ryan Patrick M.
LandOfFree
Preservative system for topically administrable... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Preservative system for topically administrable..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Preservative system for topically administrable... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2455827