| Agent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the same -> Monitor Keywords |
|
|
 
Agent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the sameRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Preparations Characterized By Special Physical Form, Tablets, Lozenges, Or PillsAgent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the same description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20060121107, Agent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the same. Brief Patent Description - Full Patent Description - Patent Application Claims
TECHNICAL FIELD [0001] The present invention relates to a gastrointestinal absorption enhancer mediated by a proton-coupled transporter and a method for preparing it. BACKGROUND OF THE INVENTION [0002] For many chronically diseased areas, oral administration is generally considered as a desirable route of pharmaceutical administration in view of convenience and cost. However, many candidate compounds for medicinal products exhibit low absorbability when administered orally since they have a low membrane permeability in the gastrointestinal tract or they are unstable therein, thereby facing a condition of being unable to maintain the blood concentration for sufficient pharmacological effects. [0003] Moreover, it is known that there are some organic compounds that show a tendency of being barely absorbed although they are reported to be recognized by influx transporters expressed in small-intestinal epithelial cells (for example, Sakamato et al., J. Antibiot. 38 (1985): 496-504, and Kelly et al., Clin. Pharmacokinet. 19 (1990): 177-196, etc.). [0004] Given this circumstance, research has been conducted in using various absorption enhancers and enzyme inhibitors to improve the absorption of compounds that are candidates for medical products. For example, Swenson et al., (Adv. Drug Del. Rev. 8 (1992): 39-92) and Kompella et al., (Adv. Drug Del. Rev. 46 (2001): 211-245) disclose methods for using absorption enhancers to improve peptide absorption. However, these methods pose the problem of cell damage by the absorption enhancers, which are primarily added to enhance absorption. [0005] Hayakawa et al., (Pharm. Res. 9 (1992): 535-540) and Zhou et al., (J. Control Rel. 29 (1994): 239-252) teach methods for adding enzyme inhibitors to inhibit decomposition and promote absorption in the gastrointestinal tract. However, these methods cause problems such that no substrate specificity is obtained in absorption. [0006] Furthermore, to improve absorption of furosemide, which is recognized by an efflux transporter in the gastrointestinal tract, addition of a pH-sensitive polymer is known (e.g., Terao et al. J. Pharm. Pharmacol. 53 (2000): 433-440). However, this reference does not suggest the use of transporters to improve gastrointestinal absorption, and has, as with the prior art methods described above, the problem of not imparting substrate specificity to gastrointestinal absorption. [0007] In addition, there have been no prior art methods that enhance the absorption of organic compounds that are, despite being substrates for influx transporters, of poor absorbability. DISCLOSURE OF THE INVENTION [0008] An object of the invention is to provide a pharmaceutical preparation that can improve cellular absorption of a pharmaceutical composition and that can provide, through oral administration or like method, a blood concentration from which sufficient remedial effects can be expected, and to provide a method for producing such a preparation. Specifically, an object of the invention is to provide a pharmaceutical preparation having an excellent gastrointestinal absorbability comprising a compound recognized by a proton-coupled transporter and a pH-sensitive polymer in an amount sufficient to give a desirable pH at which the proton-coupled transporter optimally transports the compound into a cell in the gastrointestinal tract, and a production method thereof. [0009] The inventors conducted extensive research to solve the aforementioned problems and found the facts described in (1) and (2) below: [0010] (1) Compounds recognized by peptide transporters (hereinafter sometimes referred to as "substrates"), which is one type of the proton-coupled transporters, sometimes exhibit a tendency to be gastrointestinally poorly absorbed because the amount of protons (H.sup.+), which are the driving force of peptide transporters for transporting substrates, is reduced as they travel to the lower gastrointestinal tract, and the ability of substrate transportation is thereby reduced; and [0011] (2) By adding a specific amount of pH-sensitive polymers to the substrate, the driving force of peptide transporters is increased and the gastrointestinal absorption of substrates having a tendency to be poorly absorbed is improved. [0012] The inventors carried out further development based on these findings and found that cellular uptake of a substrate is most enhanced at the pH optimum for the proton-coupled transporter. The present invention was accomplished based on these findings. [0013] In particular, the present invention provides the following: [0014] Item 1. A pharmaceutical preparation exhibiting excellent gastrointestinal absorbability comprising a compound recognized by a proton-coupled transporter and a pH-sensitive polymer, [0015] the pH-sensitive polymer being used in an amount sufficient to impart the gastrointestinal tract a pH at which the proton-coupled transporter optimally functions for cellular uptake of the compound. [0016] Item 2. A pharmaceutical preparation according to Item 1, wherein the proton-coupled transporter is an influx transporter expressed in a small-intestinal epithelial cell. [0017] Item 3. A pharmaceutical preparation according to Item 2, wherein the proton-coupled transporter is one member selected from the group consisting of a peptide transporter, monocarboxylic acid transporter, and D-cycloserine-transporting amino acid transporter. [0018] Item 4. A pharmaceutical preparation according to Item 3, wherein the proton-coupled transporter is a peptide transporter. [0019] Item 5. A pharmaceutical preparation according to Item 4, wherein the compound recognized by the peptide transporter is at least one species selected from the group consisting of peptides, .beta.-lactam antibiotics, angiotensin-converting enzyme inhibitors, antiviral agents, antitumor agents, and .omega.-amino carboxylic acids..omega. [0020] Item 6. A pharmaceutical preparation according to Item 3, wherein the proton-coupled transporter is a monocarboxylic acid transporter. [0021] Item 7. A pharmaceutical preparation according to Item 6, wherein the compound recognized by the monocarboxylic acid transporter is at least one species selected from the group consisting of lactic acid, pyruvic acid, acetic acid, propionic acid, butyric acid, glycolic acid, nicotinic acid, salicylic acid, benzoic acid, p-aminobenzoic acid, and foscarnet. Continue reading about Agent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the same... Full patent description for Agent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the same Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Agent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the same 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 Agent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the same or other areas of interest. ### Previous Patent Application: Therapeutic system comprising amoxicillin and clavulanic acid Next Patent Application: Formulations of substituted benzoxazoles Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Agent improving proton-driven transporter-mediated absorption in digestive tract and process for producing the same patent info. IP-related news and info Results in 0.10973 seconds Other interesting Feshpatents.com categories: Canon USA , Celera Genomics , Cephalon, Inc. , Cingular Wireless , Clorox , Colgate-Palmolive , Corning , Cymer , 174 |
 * Protect your Inventions * US Patent Office filing 
PATENT INFO |
|
