| Denaturants for sympathomimetic amine salts -> Monitor Keywords |
|
|
  Denaturants for sympathomimetic amine saltsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Solid Synthetic Organic Polymer As Designated Organic Active Ingredient (doai), Aftertreated Polymer (e.g., Grafting, Blocking, Etc.), Polymer Derived From Ethylenic Monomers Only, Chemical Treating Agent Contains Element Other Than C, H, O, Alkali, Or Alkaline Earth Metal, Nitrogen Or SulfurDenaturants for sympathomimetic amine salts description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060216268, Denaturants for sympathomimetic amine salts. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application claims priority to U.S. provisional application No. 60/099,712, filed Sep. 10, 1998. BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention relates to pharmaceutical compositions comprising a sympathomimetic amine salt and at least one combination inhibitor, the combination inhibitor which acts both to interfere with the isolation of the sympathomimetic amine from the composition and to interfere with the conversion of the sympathomimetic amine to another pharmacologically active compound. [0004] 2. Sympathomimetic Amines and the Problem of Unconventional Use [0005] The acid salts of sympathomimetic amines are widely used active agents in over-the-counter (OTC) pharmaceuticals. As their name suggests, this class of compounds produces pharmacological effects which mimic the activation of the sympathetic nervous system. For example, the hydrochloride salt of the sympathomimetic amine pseudoephedrine is a commonly used active ingredient in OTC decongestant products. It acts by causing adrenergic nerve endings to release norepinephrine, thereby stimulating alpha and beta norepinephrine receptors, particularly of the upper respiratory tract. This, in turn, results in vasoconstriction and shrinkage of swollen tissues in the sinuses and nasal passages. Its wide usage in numerous OTC products makes it readily available and easily accessible to the general public. When used in a recommended manner for approved indications, OTC pseudoephedrine hydrochloride pharmaceuticals are safe and effective. However, a problem arises ashen pseudoephedrine hydrochloride-containing OTC pharmaceuticals are used in an unconventional manner. Specifically, this active ingredient from OTC products is also a convenient starting material in the production of the pharmacologically active agent methamphetamine. [0006] Methamphetamine is a powerful stimulant of the central nervous system (CNS). One of its principle pharmacological effects is the release of high levels of the neurotransmitter dopamine which stimulates brain cells. The approved therapeutic uses for methamphetamine are very limited, and such approved uses are commonly associated with the treatment of obesity. However, methamphetamine's pharmacological effects make it a popular candidate for illegal use as a recreational drug rather than as a legitimate therapeutic agent. Methamphetamine has various street names which include "speed", "meth" and "crank". In its hydrochloride salt form it appears as crystals and is referred to as "ice", "crystal" and "glass". When taken intravenously or by smoking, methamphetamine causes a burst of intense sensation which has been described as highly pleasurable. Oral or intranasal use causes a less intense euphoric high. Methamphetamine addiction can occur quickly and is characterized by increasing frequency and dosage of the drug. The CNS effects of the drug include irritability, insomnia, confusion, tremors, hyperthermia, convulsions, anxiety, paranoia and aggressiveness. In more extreme cases methamphetamine causes heart rate and blood pressure changes which can ultimately contribute to cardiovascular collapse and death. [0007] As a natural progression, the illegal use of methamphetamine results in a demand for access to the drug through illicit routes. These illicit routes, in turn, are-often supplied by the illegal production of the compound. One of the main methods used in the illegal synthesis of methamphetamine is known as the ephedrine reduction method. This procedure is relatively simple, requiring only a few steps and a small number of reagents to carry out the chemical process. The starting material used in this method is either ephedrine or pseudoephedrine. Previously, ephedrine, an enantiomer of pseudoephedrine, was the starting material of choice in the production of illegal methamphetamine. However, since regulatory efforts in the United States have significantly reduced the ease by which ephedrine can be obtained, pseudoephedrine or its corresponding salts from OTC products have become the preferred starting point for the production of illicit methamphetamine. The wide public availability of pseudoephedrine hydrochloride in OTC pharmaceuticals allows illicit drug manufacturers easy and abundant access to a suitable starting material for clandestine methamphetamine chemistry. [0008] Methamphetamine abuse in the United States is expanding geographically as well as in numbers among the younger population. Traditionally the illegal use of this compound was predominantly localized in the west and southwest United States. However, trafficking patterns now have been detected in areas of the country previously not known to have problems with the illicit use of this drug, namely the Midwest. Furthermore, among young adults the illegal use of methamphetamine is increasing. For example, in 1997 4.4% of high school seniors had used crystal methamphetamine at least once in their lifetime--up from 2.7% in 1990. [0009] The increasing and broadening scope of illegal use of methamphetamine, combined with the decreased availability of ephedrine as a synthetic starting material for methamphetamine production, indicates the demand for OTC preparations of pseudoephedrine hydrochloride by illicit drug manufacturers will continue to escalate. The unconventional use of OTC pseudoephedrine can be combated by limiting the accessibility of such preparations to the general public. However, this restriction adversely impacts the consumer who seeks to use properly these safe and effective drugs and who has come to rely on ready access to them without the continuous authorization of a health care professional (e.g., physicians or pharmacists). The goal of the instant invention is to significantly deter the use of OTC products in illicit drug preparations without compromising the accessibility of these products to the general public. [0010] Prior Attempts to Minimize Illicit Use of OTC Pharmaceuticals [0011] Attempts to use the active ingredients in OTC pharmaceutical products to prepare illegal drugs is not uncommon. In response, various efforts have been made to modify pharmaceutical preparations in order to prevent this type of illicit use of these products. For example, codeine can be extracted from analgesic tablets and converted to morphine and heroin. Application WO 96/08252 disclosed codeine-containing solid dosage forms comprising components that interfere with the isolation of the active ingredient. [0012] In the case of compositions containing sympathomimetic amines, WO 97/37689 which corresponds to U.S. Ser. No. 08/937,408 filed on Apr. 1, 1997, discloses modified pharmaceutical preparations which comprise denaturing components that complicate the use of these formulations in the illegal synthesis of drugs. The main mechanism by which such a denaturant system is effective involves creating an infeasible physical separation of the sympathomimetic amine from the formulation; this denaturant system is designed to combat widely known and used methods of preparing illegal drugs from OTC products. Comparatively, the sympathomimetic amine pharmaceutical composition of the instant invention offers the unique-advantage in that it comprises a combination inhibitor which is a single component that remains with the amine when the composition is subjected to attempted separation. Such a component is not only effective against well known extraction methods commonly employed by illegal drug manufacturers, but it also deters alternate, and possibly more sophisticated means of sympathomimetic amine isolations. [0013] The combination inhibitors in the instant invention offer a second, critical advantage over previously described denaturant systems used to inhibit methamphetamine synthesis from OTC pseudoephedrine preparations; in addition to hindering the isolation of the sympathomimetic amine, these combination inhibitors also chemically interfere with the conversion of the amine to other pharmacologically active compounds. This reaction interference occurs either when the chemical conversion is carried out on the original formulation or on a composition that has undergone an extraction; interference is effective on an extracted composition since at least a portion of the combination inhibitor remains with the sympathomimetic amine under a broad range of extraction conditions. Theoretically, a combination inhibitor chemically reacts in multiple ways to prevent the conversion of the sympathomimetic amine to another compound. A combination inhibitor may react not only with itself and other reagents directed to the sympathomimetic amine, but it also may react with the amine. Since the combination inhibitor reacts with the principle starting material such as pseudoephedrine, addition of increased amounts of reactants will not likely overcome-to any significant extent the reaction of the inhibitor with the sympathomimetic amine. Furthermore, the generation of multiple side products requires sophisticated separation techniques to isolate any minimal amount of methamphetamine that may be generated. [0014] The present invention addresses the problem of the use of widely available OTC sympathomimetic amine formulations in the preparation of illegal drugs by disclosing novel pharmaceutical compositions that are impractical as starting material in illegal drug synthesis. These compositions are effective in deterring both well known extraction methods as well as different and possibly more sophisticated illegal drug production methods. Furthermore, the compositions of the present invention are not compromised in their release, bioavailability or dosing frequency relative to corresponding, undenatured sympathomimetic amine preparations presently available to the consumer. SUMMARY OF THE INVENTION [0015] The incorporation of at least one combination inhibitor in pharmaceutical compositions of sympathomimetic amines, the subject of this invention, represents a unique discovery in the area of drug formulations involving this class of active agents. The purpose of the combination inhibitor is to prevent the use of OTC sympathomimetic amine pharmaceuticals in the production of illegal drugs, particularly the synthesis of methamphetamine from pseudoephedrine. It achieves this purpose by interfering with both the isolation of the sympathomimetic amine from the composition and the conversion of the sympathomimetic amine to other pharmacologically active compounds. The combination inhibitor is present in an amount sufficient to accomplish the goal without significantly altering the release, bioavailability or dosage of the active ingredient. The advantage of the present invention is that a single component deters both traditional extraction conditions used in illegal drug synthesis as well as alternate, more sophisticated separation techniques. DETAILED DESCRIPTION OF THE INVENTION General Terms and Definitions [0016] The term "inhibitor" as used in the instant invention is any component, added to a composition containing a sympathomimetic amine, that interferes with the isolation of that sympathomimetic amine and/or interferes with the conversion of that sympathomimetic amine to another pharmacologically active compound. A single inhibitor of any class (i.e., combination, reaction or separation) or any mixture of more than one inhibitor of the same or of multiple classes of inhibitors will not significantly effect the release of the sympathomimetic amine from the formulation as compared to the undenatured composition. The term inhibitor is interchangeable with the term "denaturant". A "pharmacologically active compound" is any chemical substance that affects living tissue, producing a biological effect in a living organism. The terms "immediate release" and "modified release" are used in the instant invention as they are commonly understood in the pharmaceutical industry. For immediate release products in solid dosage form (such solid dosage forms including but not limited to tablets, capsules, powders and films), release is defined as the amount of sympathomimetic amine measured using an appropriate USP dissolution test procedure with distilled water as the medium. If no official USP dissolution test procedure has been established, (e.g., as in the case of chewable tablets), then the most appropriate USP dissolution test will apply, utilizing distilled water as the medium and taking measurements at appropriate time points up to and including the final dosing interval. For immediate release products in non-solid dosage form (such non-solid dosage forms including but not limited to liquids, syrups, elixers, liquid center oral products, creams, pastes and gels), release is defined as the amount of sympathomimetic amine measured after mixing a 1% solution of the product in distilled water at 37.degree. C. for 30 minutes. For modified release products in solid dosage form (such solid dosage forms including but not limited to tablets, capsules, powders and films), release is defined as the amount of sympathomimetic amine measured using an appropriate USP dissolution test procedure with distilled water as the medium. If no official USP dissolution test procedure has been established, (e.g., as in the case of chewable tablets), then the most appropriate USP dissolution test will apply, utilizing distilled water as the medium and taking measurements at appropriate time points up to and including the final dosing interval. For modified release products in non-solid dosage form (such non-solid dosage forms including but not limited to liquids, syrups, elixers, liquid center oral products, creams, pastes and gels), release is defined as the amount of sympathomimetic amine measured after mixing a 1% solution of the product in distilled water at 37.degree. C. for 1 hour and taking at least one additional measurement up to and including the final dosing interval. [0017] For the purposes of this invention, the term "combination inhibitor" refers to a component of a composition which both interferes with the isolation of a sympathomimetic amine from the composition and interferes with the conversion of the sympathomimetic amine to another pharmacologically active compound. The combination inhibitor interferes with such a conversion either directly from the original formulation or after attempts have been made to isolate the sympathomimetic amine. It is both the physical and chemical properties of the combination inhibitors which allow them to act as multifaceted deterrents to the use of these compositions in the preparation of other pharmacologically active compounds. Combination inhibitors of the instant invention demonstrate all of the following characteristics: (1) they significantly interfere with chemical reactions which convert the sympathomimetic amine to another pharmacologically active compound; (2) they are not readily separable from the sympathomimetic amine to an extent that they would no longer be able to significantly interfere with chemical reactions which convert the sympathomimetic amine to another pharmacologically active compound; and, (3) they may also interfere with the separation of the sympathomimetic amine from the other components of the composition. A single combination inhibitor may be used or multiple combination inhibitors may be included in the composition of the instant invention. [0018] In the present invention "reaction inhibitors" are components of a composition that mainly interfere with the conversion of sympathomimetic amines to other pharmacologically active compounds. Unlike combination inhibitors, under certain conditions a reaction inhibitor may be readily separable from the sympathomimetic amine to the extent that it no longer can significantly effect the chemical reactions which convert the sympathomimetic amine to another. pharmacologically active compound. A single reaction inhibitor may be used or multiple reaction inhibitors may be included in the composition of the instant invention. [0019] A "separation inhibitor" in the instant invention is a component of a composition that primarily interferes with the separation of the sympathomimetic amine from the composition. The interference with the separation is predominately due to the inability of the is sympathomimetic amine to be physically isolated from the composition. Separation inhibitors are of two main types: water soluble and solvent soluble. An example of a typical separation technique which may be affected by the properties of a separation inhibitor involves the use of filtration as a means of separating the sympathomimetic amine from the composition. In the case of filtration, the separation inhibitor interferes with the filtration and results in a reduced yield of separated sympathomimetic amine. Water soluble inhibitors interfere with water based separations and solvent soluble inhibitors interfere with solvent based separations. A third class of separation inhibitors can also be used in the present invention. This class includes compounds that are soluble in both aqueous and organic solvents. A single separation inhibitor may be used or multiple separation inhibitors may be included in the composition of the instant invention. [0020] Sympathomimetic Amines in OTC Pharmaceuticals and the Corresponding Pharmacologically Active Compounds Produced from the Sympathomimetic Amines Continue reading about Denaturants for sympathomimetic amine salts... Full patent description for Denaturants for sympathomimetic amine salts Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Denaturants for sympathomimetic amine salts patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Denaturants for sympathomimetic amine salts or other areas of interest. ### Previous Patent Application: Absorbable alpha-cyanoacrylate compositions Next Patent Application: Dendrimers as molecular translocators Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Denaturants for sympathomimetic amine salts patent info. IP-related news and info Results in 0.83455 seconds Other interesting Feshpatents.com categories: Electronics: Semiconductor , Audio , Illumination , Connectors , Crypto , |
||
