Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
1999-10-08
2002-08-06
Azpuru, Carlos (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S502000
Reexamination Certificate
active
06428814
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to nanoparticulate compositions comprising particles of an active agent and one or more cationic surface stabilizers adsorbed to the surface of the active agent. The nanoparticulate compositions have superior adhesion properties to biological surfaces, such as mucous, skin, hair, plant tissue, etc.
2. Description of the Related Art
Nanoparticulate compositions, which were first described in U.S. Pat. No. 5,145,684 (“the '684 Patent”), comprise a poorly soluble crystalline drug and a non-crosslinked surface stabilizer adsorbed to the surface of the drug. Nanoparticulate compositions are superior to macro-sized particulate drug formulations as nanoparticulate drug formulations can exhibit reduced toxicity and enhanced efficacy (U.S. Pat. No. 5,399,363), enhanced bioavailability (U.S. Pat. No. 5,662,883), and enhanced stability (U.S. Pat. No. 5,665,331). The '684 patent teaches that ionic and non-ionic surface stabilizers are preferred for nanoparticulate compositions.
The '684 patent describes a method of screening drugs to identify useful surface stabilizers that enable the production of a nanoparticulate composition. Not all surface stabilizers will function to produce a stable, non-agglomerated nanoparticulate composition for all drugs. Moreover, known surface stabilizers may be unable to produce a stable, non-agglomerated nanoparticulate composition for certain drugs. Thus, there is a need in the art to identify new surface stabilizers useful in making nanoparticulate compositions. Additionally, such new surface stabilizers may have superior properties over prior known surface stabilizers.
Exemplary known surface stabilizers useful in stabilizing and preventing the aggregation of nanoparticulate active agents are described in the '684 patent. Known and particularly preferred surface stabilizers for nanoparticulate compositions include tyloxapol (U.S. Pat. No. 5,429,824), polyalkylene block copolymers (U.S. Pat. No. 5,565,188), sulfated non-ionic block copolymers (U.S. Pat. No. 5,569,448), high molecular weight, linear, poly(ethylene oxide) polymers (U.S. Pat. No. 5,580,579), butylene oxide-ethylene oxide block copolymers (U.S. Pat. No. 5,587,143), hydroxypropyl cellulose (U.S. Pat. No. 5,591,456), and sugar based surface stabilizers (U.S. Pat. No. 5,622,938).
Several prior art methods for minimizing nanoparticle aggregation following heat sterilization utilize non-ionic surface stabilizers and cloud point modifiers. Such methods include adding an anionic or cationic cloud point modifier to a nanoparticulate composition (U.S. Pat. No. 5,298,262); adding a non-ionic surface stabilizer and a non-ionic cloud point modifier to a nanoparticulate composition (U.S. Pat. No. 5,346,702); adding a non-ionic surface stabilizer and a charged phospholipid as a cloud point modifier to a nanoparticulate composition (U.S. Pat. No. 5,470,583); and adding a non-ionic surface modifier and a charged phospholipid to a nanoparticulate composition (U.S. Pat. Nos. 5,336,507 and 5,470,583).
Anionic and non-ionic surface stabilizers for nanoparticulate compositions have also been described. For example, U.S. Pat. No. 5,593,657 discloses nanoparticulate x-ray contrast compositions comprising anionic and non-ionic surface stabilizers. The nanoparticulate compositions adhere to the mucosal surface of the gastrointestinal tract (GIT), allowing for diagnostic examination of the GIT. U.S. Pat. No. 5,326,552 describes a nanoparticulate x-ray contrast composition having a high molecular weight non-ionic surface stabilizer and a cloud point modifier. In addition, U.S. Pat. No. 5,447,710 describes nanoparticulate x-ray contrast compositions having high molecular weight non-ionic surface stabilizers and a cloud point modifier.
Cationic surfactants are used in a wide variety of products and applications. For example, they are often used in cleaning, degreasing, and detergent compositions (U.S. Pat. Nos. 5,935,921, 5,935,272, and 5,912,219), liquid cleansers, bar soaps (U.S. Pat. No. 5,935,920), pesticides (U.S. Pat. No. 5,935,908), hair care products, such as shampoos and conditioners (U.S. Pat. Nos. 5,935,561, 5,932,535, and 5,932,202), laundry detergent (U.S. Pat. Nos. 5,935,271 and 5,929,024), photographic materials (U.S. Pat. No. 5,932,404), fabric softening compositions (U.S. Pat. No. 5,932,253), toothpaste compositions (U.S. Pat. No. 5,932,193), bleaching agents (U.S. Pat. No. 5,929,015), textile treatment compositions, automatic dishwashing detergent powders, cosmetics, environmental remediation (contaminated soil/groundwater remediation), enhanced oil recovery, and in medical applications, such as application to the lungs of premature infants.
There is a need in the art for effective, stable compositions having excellent adhesion properties to biological surfaces. The present invention satisfies these needs.
SUMMARY OF THE INVENTION
The present invention is directed to stable bioadhesive nanoparticulate compositions comprising an active agent and at least one cationic surface stabilizer. The active agent can be either crystalline, semi-crystalline, or amorphous, or liquid at or near room temperature. The active agent particles can be dissolved or dispersed in a liquid medium or used in dry form.
In one embodiment, described are stable bioadhesive nanoparticulate compositions comprising particles of a poorly water-soluble active agent and, adsorbed to the surface of the agent, at least one cationic surface stabilizer. The active agent can be either crystalline, semi-crystalline, or amorphous. The active agent particles of the nanoparticulate composition have an effective average particle size of less than about 4000 nm. The active agent particles can be dispersed in a liquid medium or used in dry form.
In yet another embodiment, described are stable bioadhesive nanoparticulate compositions comprising particles of a water-soluble active agent and, adsorbed to the surface of the agent, at least one cationic surface stabilizer. The active agent can be either crystalline, semi-crystalline, or amorphous. The active agent particles of the nanoparticulate composition have an effective average particle size of less than about 4000 nm. The active agent particles can be dispersed in a liquid medium or used in dry form.
In a further embodiment, described are stable bioadhesive nanoparticulate compositions comprising liquid particles of a poorly water-soluble active agent and, adsorbed to the surface of the liquid particles, at least one cationic surface stabilizer. The active agent is in a liquid state at or near room temperature. In this embodiment, the nanoparticulate composition is in the form of an emulsion. The active agent emulsion droplets of the nanoparticulate composition have an effective average particle size of less than about 4000 nm. The active agent emulsion droplets are dispersed in a liquid medium in which they are poorly soluble, such as water.
In a further embodiment, described are stable bioadhesive nanoparticulate compositions comprising liquid particles of a water-soluble active agent and, adsorbed to the surface of the liquid particles, at least one cationic surface stabilizer. The active agent is in a liquid state at or near room temperature. In this embodiment, the nanoparticulate composition is in the form of an emulsion. The active agent emulsion droplets of the nanoparticulate composition have an effective average particle size of less than about 4000 nm. The active agent emulsion droplets are dispersed in a liquid medium in which they are poorly soluble, such as mineral oil, vegetable oils (corn, safflower, olive, etc.), or a hydrocarbon.
Also described are stable bioadhesive nanoparticulate compositions comprising active agent particles dissolved or dispersed in liquid droplets of a poorly water-soluble liquid and, adsorbed to the surface of the liquid droplets, at least one cationic surface stabilizer. For this composition, the liquid droplets comprising active agent are dispersed in a liqu
Bosch H. William
Cooper Eugene R.
McGurk Simon L.
Azpuru Carlos
Elan Pharma International Ltd.
Foley & Lardner
LandOfFree
Bioadhesive nanoparticulate compositions having cationic... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Bioadhesive nanoparticulate compositions having cationic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bioadhesive nanoparticulate compositions having cationic... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2887619