WO2005011629A1 - Bioactive compositions comprising triazines - Google Patents

Bioactive compositions comprising triazines Download PDF

Info

Publication number
WO2005011629A1
WO2005011629A1 PCT/US2004/024515 US2004024515W WO2005011629A1 WO 2005011629 A1 WO2005011629 A1 WO 2005011629A1 US 2004024515 W US2004024515 W US 2004024515W WO 2005011629 A1 WO2005011629 A1 WO 2005011629A1
Authority
WO
WIPO (PCT)
Prior art keywords
bioactive
compound
group
triazine
composition according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2004/024515
Other languages
English (en)
French (fr)
Inventor
Hassan Sahouani
Robert A. Scherrer
Mouhannad Jumaa
Isidro Angelo Eleazar Zarraga
Kim M. Vogel
Dennis E. Vogel
Wei Zou
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
3M Innovative Properties Co
Original Assignee
3M Innovative Properties Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 3M Innovative Properties Co filed Critical 3M Innovative Properties Co
Priority to AU2004261243A priority Critical patent/AU2004261243A1/en
Priority to BRPI0413164-9A priority patent/BRPI0413164A/pt
Priority to JP2006522067A priority patent/JP2007500713A/ja
Priority to US10/595,050 priority patent/US20080039533A1/en
Priority to MXPA06001054A priority patent/MXPA06001054A/es
Priority to EP04779530A priority patent/EP1651185A1/en
Priority to CA002533128A priority patent/CA2533128A1/en
Publication of WO2005011629A1 publication Critical patent/WO2005011629A1/en
Priority to IL173301A priority patent/IL173301A0/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
    • C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
    • C07D251/18—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • BIOACTIVE COMPOSITIONS COMPRISING TRIAZINES Field The present invention relates to bioactive compositions comprising a bioactive compound and a triazine compound.
  • the present invention relates to pharmaceutical compositions comprising a drug.
  • Background The delivery of a bioactive compound to a living organism is generally affected by a number of parameters beyond the actual chemical identity and pharmacological activity of the bioactive compound.
  • Formulation additives other than the bioactive compound are commonly used to alter the physicochemical properties of a product having bioactive function.
  • pharmaceutical dosage forms i.e., dosages containing a drug or active pharmaceutical ingredient
  • Each R 2 is independently selected from any electron donating group, electron withdrawing group and electron neutral group.
  • R 3 is selected from the group consisting of: substituted heteroaromatic rings, unsubstituted heteroaromatic rings, substituted heterocyclic rings, and unsubstituted heterocyclic rings, that are linked to the triazine group through a nitrogen atom within a ring of R 3 .
  • -Another aspectof the invention includes a method for increasing the solubility of a bioactive compound in a bioactive composition comprising providing a bioactive compound, providing a triazine compound comprising:
  • the bioactive compound, the triazine compound, and a solvent are combined to form a composition characterized in that the amount of dissolved bioactive compound in the composition is greater than the amount of bioactive compound dissolvable in the same composition not containing the triazine compound.
  • the triazine can be used to increase the amount of bioactive compound that can be dissolved in a composition
  • the triazine compound is characterized in that each R 2 is independently selected from any electron donating group, electron withdrawing group and electron neutral group.
  • R 3 is selected from the group consisting of: substituted heteroaromatic rings, unsubstituted heteroaromatic rings, substituted heterocyclic rings, and unsubstituted heterocyclic rings, that are linked to the triazme group through a nitrogen atom within a ring of R .
  • the present invention includes a method for increasing the stability of a bioactive compound in a bioactive composition comprising providing a bioactive compound, and providing a triazine compound comprising:
  • the bioactive compound, the triazme compound, and a solvent are combined to form a bioactive composition characterized in that the stability of the bioactive compound in the composition is greater than the stability of the bioactive compound in the same composition not containing the triazine compound.
  • the triazine compound can be used to stabilize the bioactive compound.
  • the triazme compound is characterized in that each R 2 is independently selected from any electron donating group, electron withdrawing group and electron neutral group.
  • R 3 is selected from the group consisting of: substituted heteroaromatic rings, unsubstituted heteroaromatic rings, substituted heterocyclic rings, and unsubstituted heterocyclic rings, that are linked to the triazine group through a nitrogen atom within a ring of R 3 .
  • Each R 2 is independently selected from any electron donating group, electron withdrawing group and electron neutral group.
  • R 3 is selected from the group consisting of substituted and unsubstituted heteroaromatic rings linked to the triazine group through a nitrogen atom within a ring of R 3 .
  • Formula I above shows an orientation of the carboxy (-COOH) group which is para with respect to the amino linkage to the triazme backbone of the compound.
  • the carboxy group may also be meta with respect to the amino linkage, as shown in formula II.
  • R 2 is independently selected from any electron donating group, electron withdrawing group and electron neutral group.
  • R 2 is hydrogen or a substituted or unsubstituted alkyl group. More preferably, R 2 is hydrogen, an unsubstituted alkyl group, or an alkyl group substituted with a hydroxy, ether, ester, sulfonate, or halide functional group. Most preferably R 2 is hydrogen.
  • R 3 comprises a heteroaromatic ring derived from pyridine or imidazole.
  • a substituent for the heteroaromatic ring R 3 may be selected from, but is not limited to, any of the following substituted and unsubstituted groups: alkyl, carboxy, amino, alkoxy, thio, cyano, amide, sulfonate, hydroxy, halide, perfluoroalkyl, aryl, ether, and ester.
  • R 3 examples include, but are not limited to: 4-(dimethylamino)pyridium-l-yl, 3- methylimidazolium- 1 -yl, 4-(pyrrolidin- 1 -yl)pyridium- 1 -yl, 4-isopropylpyridinium- 1 -yl, 4-[(2-hydroxyethyl)methylamino]pyridinium- 1 -yl, 4-(3 -hydroxypropyl)pyridinium- 1 -yl, 4-methylpyridinium-l-yl, quinolinium-1-yl, 4-tert-butylpyridinium-l-yl, and 4-(2-sulfoethyl)pyridinium-l-yl, shown in formulae IN to XIII below.
  • heterocyclic rings that R 3 may be selected from include, for example, morpholine, pyrrolidine, piperidine, and piperazine.
  • R 3 group shown in formula N above may also have a substituent group other than methyl attached to the imidazole ring, as shown below,
  • R- 4 is hydrogen or a substituted or unsubstituted alkyl group.
  • 1 ⁇ is hydrogen, an unsubstituted alkyl group, or an alkyl group substituted with a hydroxy, ether, ester, sulfonate, or halide functional group.
  • 4 may be propyl sulfonic acid, methyl, or oleyl.
  • triazme of formula I is neutral, however triazine molecules of the present invention may exist in an ionic form wherein they contain at least one formal positive charge. In a preferred embodiment, the triazine molecule may be zwitterionic.
  • R 3 is a pyridine ring linked to the triazine group through the nitrogen atom of the pyridine ring.
  • the pyridine nitrogen carries a positive charge and one of the carboxy functional groups carries a negative charge (and has a dissociated cation, such as a hydrogen atom), -COO " .
  • triazine derivatives with formula I may be prepared as aqueous solutions, or may be prepared as salts which can later be re-dissolved to form an aqueous solution.
  • a typical synthetic route for the triazine molecules shown in I above involves a two step process.
  • the triazine contains at least one formal positive charge.
  • the triazine may also be zwitterionic, that is, carrying at least one formal positive and one formal negative charge.
  • Zwitterionic triazines of the present invention will carry at least one negative charge through a carboxy group having a dissociated hydrogen atom, -COO " .
  • the negative charge may be shared among the multiple carboxy functional groups present, such that a proper representation of the triazine consists of two or more resonance structures.
  • the negative or partial negative charges may be carried by other acid sensitive groups in the triazine.
  • the triazine can be used to form a chromonic phase or assembly when in an aqueous solution.
  • Chromonic phases or assemblies are well known (see, for example, Handbook of Liquid Crystals, Volume 2B, Chapter XNIII, Chromonics, John
  • Lydon pp. 981-1007, 1998) and consist of stacks of flat, multi-ring aromatic molecules.
  • the molecules typically consist of a hydrophobic core surrounded by hydrophilic groups.
  • the stacking takes on a number of morphologies, but is typically characterized by a tendency to form columns created by a stack of layers. Ordered stacks of molecules can be formed that grow with increasing concentration, but they are distinct from micellar phases in that they generally do not have surfactant-like properties and do not exhibit a critical micellar concentration.
  • the chromonic ⁇ phase typically exhibits a schlieren texture, which is characterized by regions of varying index of refraction in a transparent medium.
  • the ordered chromonic phase can contribute to increased solubility of a bioactive compound by providing sites within the ordered stacks where the bioactive compounds may reside and where they will have little interaction with the bulk solvent, such as the aqueous phase, where the bioactive compounds may have lower solubility.
  • the chromonic ordered phase may be able to isolate the bioactive compounds from the solvent and potentially from each other, since the bioactive compounds may be interleaved or intercalated on a molecular scale between the triazme molecules.
  • compositions of the present invention may comprise a surfactant.
  • Suitable surfactants include, for example, long chain saturated fatty acids or alcohols and mono or poly-unsaturated fatty acids or alcohols. Oleyl phosphonic acid is a preferred surfactant.
  • compositions of the present invention may comprise an alkaline compound.
  • suitable alkaline compounds include ethanolamine, sodium or lithium hydroxide, or amines such as mono, di, triamines or polyamines.
  • alkaline compounds aid in dissolving the triazine compound.
  • a bioactive compound as used herein is defined as a compound intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure or function of a living organism. Examples of bioactive compounds include drugs, herbicides, pesticides, pheromones, and antifungal agents.
  • Drugs are bioactive compounds of particular interest.
  • herbicides and pesticides are examples of bioactive compounds intended to have a negative effect on a living organism, such as a plant or pest.
  • any type of drug may be employed with compositions of the present invention, of particular interest are drugs that are relatively unstable when formulated as solution, suspension, or semi-solid dosage forms, and those that have poor solubility in conventional carriers.
  • the weight ratio of drug to the triazine compound will typically be less than about 10:1, usually less than about 1.5:1, often less than about 1:1, and sometimes less than about 1:2.
  • the triazine compound is generally itself non-therapeutic.
  • the triazine compound may alter the dosage form and may influence, for example, the amount of drug delivered to a site in a living organism in a bioavailable form, which can clearly affect the therapeutic activity of the drug. Although this affect on therapeutic activity is a direct result of the function of the triazine compound in the present invention, it is normally preferred that the triazine compound itself is non-therapeutic once it is dissociated from the drug.
  • the triazine compound has no appreciable therapeutic activity when delivered to an organism, e.g., such as an animal, in the form of isolated molecules.
  • the triazine compound is generally largely inert with relation to biological interactions with an organism and will thus serve only as a carrier for the drug.
  • the triazine compound is preferably non-toxic, non-mutagenic, and non- irritating.
  • compositions of the present invention may find use in a variety of routes of drug delivery, including oral, such as tablets, capsules, liquid solutions, and syrups; by intravenous, intramuscular, or intraperitoneal injection, such as aqueous or oil solutions or suspensions; by subcutaneous injection; or by incorporation into transdermal, topical, or mucosal dosage forms, such as creams, gels, adhesive patches, suppositories, and nasal sprays.
  • routes of drug delivery including oral, such as tablets, capsules, liquid solutions, and syrups; by intravenous, intramuscular, or intraperitoneal injection, such as aqueous or oil solutions or suspensions; by subcutaneous injection; or by incorporation into transdermal, topical, or mucosal dosage forms, such as creams, gels, adhesive patches, suppositories, and nasal sprays.
  • Compositions of the present invention may also be implanted or injected into various internal organs and tissues, for example, cancerous tumors, or may be directly applied to internal
  • compositions of the present invention may also be suitable for use in inhalation dosage forms, such as pressurized meter dose inhalers, for example, those described in U. S. Patent No. 5, 836, 299 (Kwon, et al.), the disclosure of which is incorporated by reference; and nebulizers, for example, those described in U. S. Patent No. 6, 338, 443 (Piper, et al.), the disclosure of which is incorporated by reference, hi one type of embodiment a liquid or semi-solid composition of the present invention may be contained within a capsule for oral delivery that is designed to release the composition at a specific location within the gastrointestinal tract.
  • pressurized meter dose inhalers for example, those described in U. S. Patent No. 5, 836, 299 (Kwon, et al.), the disclosure of which is incorporated by reference
  • nebulizers for example, those described in U. S. Patent No. 6, 338, 443 (Piper, et al.), the disclosure
  • composition of the present invention may be the discontinuous phase of a water-in-oil emulsion.
  • Compositions of the present invention can optionally include one or more other ingredients in addition to the bioactive compound and the triazine compound, such as, for example, initiators, fillers, plasticizers, cross-linkers, tackifiers, binders, antioxidants, stabilizers, surfactants, solubilizers, buffers, permeation enhancers, adhesives, viscosity enhancing agents, coloring agents, flavoring agents, and mixtures thereof.
  • a combination of bioactive compounds may also be used.
  • the present invention comprises a method for preparing a bioactive composition
  • a method for preparing a bioactive composition comprising provision of a bioactive compound and provision of a triazine compound comprising a molecule of formula I or II, wherein each R 2 is independently selected from any electron donating group, electron withdrawing group and electron neutral group and R 3 is selected from the group consisting of substituted and unsubstituted heteroaromatic rings linked to the triazine group through a nitrogen atom within a ring of R 3 , and proton tautomers and salts thereof.
  • the bioactive compound, the triazine compound, and a solvent are combined to form a bioactive composition.
  • the solvent is a liquid or semi-solid capable of dissolving or dispersing the bioactive compound and the triazine compound.
  • the solvent may remain in the final dosage form.
  • a pharmaceutically acceptable excipient such as water, ethanol, propylene glycol, or 1,1,1,2-tetrafluoroethane
  • the solvent may be used for processing purposes and be removed prior to preparation of a final dosage form.
  • Process solvents may be removed by any process known to one of skill in the art, including for example, distillation or solvent stripping, air impingement drying, air drying or evaporation, and/or vacuum drying.
  • Typical process solvents include, for example, methanol, ethyl acetate, heptane, hexane, and acetone. Solvents that are acceptable for use in the final dosage form, such as water, may also be used as process solvents.
  • Compositions of the present invention may be prepared by mixing triazines with a bioactive compound. For example, the triazine may be dissolved in an aqueous solution and the bioactive compound is added to the triazine solution. It may be desirable to prepare a concentrated stock solution of triazine and bioactive compound that is subsequently diluted to prepare a final dosage form. Likewise, additional ingredients may be added to the initial triazine solution or be added to the resulting mixtures of triazine and bioactive.
  • the triazine solution exhibits a chromonic M or N phase.
  • This chromonic solution may be moderately or highly viscous.
  • Typical solution viscosities for a chromonic solution containing 15% by weight triazine will be between about 100 and about 700 centipoise at room temperature, and more preferably between about 200 and 400 centipoise at room temperature. It may be desirable to heat one or more of the intermediate solutions to assist in dissolution or mixing of one or more of the ingredients of the final dosage form.
  • the bioactive compound may be dissolved in an aqueous solution and the triazine is added to the bioactive compound solution.
  • the bioactive compound, the triazine compound, and a solvent are combined to form a bioactive composition characterized in that the amount of dissolved bioactive compound in the composition is greater than the amount of dissolved bioactive compound in the same composition not containing the triazine compound.
  • the ratio of the amount of bioactive compound dissolvable in a composition using triazine compound to the amount of bioactive compound dissolvable in the same composition not containing the triazine compound can be greater than about 1.5:1 and in some instances greater than 2:1. In some embodiments the ratio of the amount of bioactive compound dissolvable in the composition using triazine compound to the amount of bioactive compound dissolvable in the same composition not containing the triazine compound may be greater than about 100:1.
  • the present invention comprises a method for increasing the stability of a bioactive compound in a bioactive composition by proving a bioactive compound and a triazine compound comprising a molecule of formula I or II, wherein each R 2 is independently selected from any electron donating group, electron withdrawing group and electron neutral group and R 3 is selected from the group consisting of substituted and unsubstituted heteroaromatic rings linked to the triazine group through a nitrogen atom within a ring of R 3 , and proton tautomers and salts thereof.
  • measurement of 95% of the initial amount of bioactive compound is equivalent to a reduction of 5% of the initial amount of bioactive compound.
  • Dosage forms using or including the methods and compositions of the present invention may be characterized in that the reduction in amount of bioactive compound over time is less than the reduction in amount of bioactive compound over time in the same dosage form not containing the triazine compound.
  • the lessened reduction in amount of bioactive compound is typically observed over lengths of time ranging from 4 weeks to 3 years, including for example, 1 month, 3 months, 6 months, 1 year, and 2 years.
  • the ratio of the reduction in amount of bioactive compound over time compared to the reduction in amount of bioactive compound over time for a like dosage form not containing the triazine compound is preferably less than about 3:4, more preferably less than about 1 :2, and most preferably less than about 1 :4.
  • the dosage form may comprise more than one bioactive compound, for instance, a combination of two bioactives, such as enalapril and felodipine, and an improvement in stability of such a dosage form may be seen in one or both of the bioactive compounds.
  • the present invention comprises a method for drug delivery comprising provision of a bioactive composition comprising a drug and a triazine compound comprising a molecule of formula I or II, wherein each R 2 is independently selected from any electron donating group, electron withdrawing group and electron neutral group and R 3 is selected from the group consisting of substituted and unsubstituted heteroaromatic rings linked to the triazine group through a nitrogen atom within a ring of R 3 , and proton tautomers and salts thereof.
  • the bioactive composition is delivered to an organism, and allowed to remain in contact with a portion of the organism for a period of time sufficient to provide a therapeutic effect resulting from delivery of the drug.
  • the bioactive composition may be delivered to an animal, e.g., orally, by intravenous, subcutaneous, intratumoral, or intramuscular injection, oral or nasal inhalation, or any other suitable method for drug delivery known in the art.
  • Examples Examples 1-4 Imiquimod solubility in basic solutions containing a triazine compound was determined as follows. A solution was prepared by adding approximately 1 g of l-[4,6- bis(4-carboxyamlino)-l,3,5-triazin-2-yl]-4-(dimethylamino)pyridinium chloride to 9 g of distilled water containing a molar equivalent amount of a counterion base. The solution was heated to 70°C, an excess of imiquimod (approximately 0.1 g) was added to the solution, and stirred for approximately 14 hours. The solution was then allowed to cool to room temperature for at least 5 hours prior to filtering through a 5.0 ⁇ m filter to remove the undissolved solids.
  • Imiquimod concentration was then determined by HPLC, at which time the solution was further filtered through a 0.45 ⁇ m filter.
  • concentration of triazine compound in the prepared solution, the type of counterion base, and the measured imiquimod solubility are shown in Table 1 below.
  • Imiquimod solubility in a buffer solution having a pH of 6.05 and not containing a triazine compound is 0.02 mg/mL.
  • Imiquimod solubility in a buffer solution having a pH of 7.82 and not containing a triazine compound is 0.0012 mg/mL.
  • Lidocaine solubility in solutions containing a triazine compound was determined as follows.
  • a stock solution was prepared by combining l-[4,6-bis(4-carboxyanilino)- l,3,5-triazin-2-yl]-4-(dimethylamino)pyridinium chloride (6.0027 g), ethanolamine (1.35 g), and distilled water (18.00 g). This solution was stirred until the solids were dissolved to give a solution having 20% w/w triazine compound.
  • Solutions having varying concentration of triazine (shown in Table 2) were prepared by removing an aliquot from the stock solution and diluting the aliquot with distilled water to reach each triazine concentration.
  • lidocaine An excess (at least 3-fold) of lidocaine was added to each of the solutions and shaken at ambient temperature for at least 24 hours.
  • the solutions were filtered through a 0.45 ⁇ m filter to remove the undissolved solids and then analyzed by HPLC for lidocaine concentration.
  • the concentration of triazine compound in the prepared solution and the measured lidocaine solubility are shown in Table 2 below.
  • Examples 10-14 Alendronate solubility in solutions containing a triazine compound was determined as follows. A stock solution was prepared by combining l-[4,6-bis(4-carboxyanilino)- l,3,5-triazin-2-yl]-4-(dimethylamino)pyridinium chloride (4.02169 g), ethanolamine (0.8898 g), and distilled water (12.0019 g). This solution was stirred until the solids were dissolved to give a solution having 20% w/w triazine compound. Solutions having varying concentration of triazine (shown in Table 3) were prepared by removing an aliquot from the stock solution and diluting the aliquot with distilled water to reach the desired triazine concentration.
  • the concentration of triazine compound and the measured alendronate solubility are shown in Table 3 below.
  • the solubility of alendronate in distilled water was determined by adding an excess of alendronate to distilled water, shaking for 24 hours, filtering, and analyzing by capillary electrophoresis, as above.
  • the solubility of alendronate in distilled water was 3.1% [w/w].

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US2004/024515 2003-07-31 2004-07-29 Bioactive compositions comprising triazines Ceased WO2005011629A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
AU2004261243A AU2004261243A1 (en) 2003-07-31 2004-07-29 Bioactive compositions comprising triazines
BRPI0413164-9A BRPI0413164A (pt) 2003-07-31 2004-07-29 composições bioativas compreendendo as triazinas
JP2006522067A JP2007500713A (ja) 2003-07-31 2004-07-29 トリアジンを含む生理活性組成物
US10/595,050 US20080039533A1 (en) 2003-07-31 2004-07-29 Bioactive Compositions Comprising Triazines
MXPA06001054A MXPA06001054A (es) 2003-07-31 2004-07-29 Composiciones bioactivas que comprenden triazinas.
EP04779530A EP1651185A1 (en) 2003-07-31 2004-07-29 Bioactive compositions comprising triazines
CA002533128A CA2533128A1 (en) 2003-07-31 2004-07-29 Bioactive compositions comprising triazines
IL173301A IL173301A0 (en) 2003-07-31 2006-01-23 Bioactive compositions comprising triazines

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US49163103P 2003-07-31 2003-07-31
US49163803P 2003-07-31 2003-07-31
US60/491,631 2003-07-31
US60/491,638 2003-07-31

Publications (1)

Publication Number Publication Date
WO2005011629A1 true WO2005011629A1 (en) 2005-02-10

Family

ID=34118876

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2004/024515 Ceased WO2005011629A1 (en) 2003-07-31 2004-07-29 Bioactive compositions comprising triazines
PCT/US2004/024429 Ceased WO2005012488A2 (en) 2003-07-31 2004-07-29 Compositions for encapsulation and controlled release

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US2004/024429 Ceased WO2005012488A2 (en) 2003-07-31 2004-07-29 Compositions for encapsulation and controlled release

Country Status (11)

Country Link
US (2) US20080039533A1 (enExample)
EP (2) EP1651035A2 (enExample)
JP (2) JP2007500713A (enExample)
KR (2) KR20060056354A (enExample)
AU (2) AU2004261987A1 (enExample)
BR (2) BRPI0413164A (enExample)
CA (2) CA2534042A1 (enExample)
IL (2) IL173300A0 (enExample)
MX (2) MXPA06001054A (enExample)
RU (2) RU2006102188A (enExample)
WO (2) WO2005011629A1 (enExample)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007072083A1 (en) 2005-12-23 2007-06-28 Prosidion Limited Treatment of type 2 diabetes with a combination of dpiv inhibitor and metformin or thiazolidinedione
WO2007075282A1 (en) * 2005-12-19 2007-07-05 3M Innovative Properties Company Hierachical chromonic structures
WO2007079083A1 (en) * 2005-12-28 2007-07-12 3M Innovative Properties Company Encapsulated chromonic particles
WO2008054866A3 (en) * 2006-05-23 2008-06-19 3M Innovative Properties Co Method of making ordered nanostructured layers
WO2008060660A3 (en) * 2006-04-13 2008-07-03 3M Innovative Properties Co Method and apparatus for forming crosslinked chromonic nanoparticles
US7582330B2 (en) 2004-11-24 2009-09-01 3M Innovative Properties Counsel Method for making metallic nanostructures
US7601769B2 (en) 2005-12-19 2009-10-13 3M Innovative Peroperties Company Multilayered chromonic structures
US7629027B2 (en) 2005-10-14 2009-12-08 3M Innovative Properties Company Method for making chromonic nanoparticles
US7687115B2 (en) 2004-11-24 2010-03-30 3M Innovative Properties Company Method for making nanostructured surfaces
US7718716B2 (en) 2005-10-14 2010-05-18 3M Innovative Properties Company Chromonic nanoparticles containing bioactive compounds
US7807661B2 (en) 2005-12-08 2010-10-05 3M Innovative Properties Company Silver ion releasing articles and methods of manufacture

Families Citing this family (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040265351A1 (en) 2003-04-10 2004-12-30 Miller Richard L. Methods and compositions for enhancing immune response
PH12006500401A1 (en) * 2003-08-27 2005-03-10 3M Innovative Properties Company Aryloxy and arylalkyleneoxy substituted imidazoquinolines
CA2540598C (en) 2003-10-03 2013-09-24 3M Innovative Properties Company Pyrazolopyridines and analogs thereof
EP1673087B1 (en) 2003-10-03 2015-05-13 3M Innovative Properties Company Alkoxy substituted imidazoquinolines
CA2547020C (en) 2003-11-25 2014-03-25 3M Innovative Properties Company 1h-imidazo[4,5-c]pyridine-4-amine derivatives as immune response modifier
US8541438B2 (en) 2004-06-18 2013-09-24 3M Innovative Properties Company Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines
US7247723B2 (en) 2004-11-24 2007-07-24 3M Innovative Properties Company Metallic chromonic compounds
AU2005322898B2 (en) 2004-12-30 2011-11-24 3M Innovative Properties Company Chiral fused (1,2)imidazo(4,5-c) ring compounds
JP5313502B2 (ja) 2004-12-30 2013-10-09 スリーエム イノベイティブ プロパティズ カンパニー 置換キラル縮合［１，２］イミダゾ［４，５−ｃ］環状化合物
WO2006086449A2 (en) 2005-02-09 2006-08-17 Coley Pharmaceutical Group, Inc. Alkyloxy substituted thiazoloquinolines and thiazolonaphthyridines
JP2008530252A (ja) 2005-02-09 2008-08-07 コーリー ファーマシューティカル グループ，インコーポレイテッド オキシムおよびヒドロキシルアミンで置換されたチアゾロ［４，５−ｃ］環化合物ならびに方法
AU2006216997A1 (en) * 2005-02-11 2006-08-31 Coley Pharmaceutical Group, Inc. Substituted imidazoquinolines and imidazonaphthyridines
WO2006091568A2 (en) 2005-02-23 2006-08-31 Coley Pharmaceutical Group, Inc. Hydroxyalkyl substituted imidazonaphthyridines
US8158794B2 (en) * 2005-02-23 2012-04-17 3M Innovative Properties Company Hydroxyalkyl substituted imidazoquinoline compounds and methods
US8178677B2 (en) * 2005-02-23 2012-05-15 3M Innovative Properties Company Hydroxyalkyl substituted imidazoquinolines
WO2006091647A2 (en) * 2005-02-23 2006-08-31 Coley Pharmaceutical Group, Inc. Method of preferentially inducing the biosynthesis of interferon
US9233094B2 (en) 2005-05-04 2016-01-12 Medigene Ag Method of administering a cationic liposomal preparation
ZA200803029B (en) 2005-09-09 2009-02-25 Coley Pharm Group Inc Amide and carbamate derivatives of alkyl substituted /V-[4-(4-amino-1H-imidazo[4,5-c] quinolin-1-yl)butyl] methane-sulfonamides and methods
AU2006287270A1 (en) * 2005-09-09 2007-03-15 Coley Pharmaceutical Group, Inc. Amide and carbamate derivatives of N-{2-[4-amino-2- (ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}methanesulfonamide and methods
ES2429170T3 (es) * 2005-11-04 2013-11-13 3M Innovative Properties Company 1H-Imidazoquinolinas sustituidas con hidroxilo y alcoxilo y métodos
US8951528B2 (en) 2006-02-22 2015-02-10 3M Innovative Properties Company Immune response modifier conjugates
US8329721B2 (en) * 2006-03-15 2012-12-11 3M Innovative Properties Company Hydroxy and alkoxy substituted 1H-imidazonaphthyridines and methods
MX2008011978A (es) 2006-03-22 2009-04-22 Medigene Ag Tratamiento del cancer de seno negativo al triple receptor.
WO2008030511A2 (en) * 2006-09-06 2008-03-13 Coley Pharmaceuticial Group, Inc. Substituted 3,4,6,7-tetrahydro-5h, 1,2a,4a,8-tetraazacyclopenta[cd]phenalenes
JP2010514679A (ja) * 2006-12-22 2010-05-06 スリーエム イノベイティブ プロパティズ カンパニー 制御放出組成物及び方法
US20110135571A1 (en) * 2008-02-22 2011-06-09 Wenbin Lin Hybrid nanoparticles as anti-cancer therapeutic agents and dual therapeutic/imaging contrast agents
AU2010213530B2 (en) 2009-02-13 2015-09-03 Monsanto Technology Llc Encapsulation of herbicides to reduce crop injury
WO2010129728A2 (en) * 2009-05-06 2010-11-11 3M Innovative Properties Company Articles with shell structures including a cell extractant and biodetection methods thereof
EP3222621B1 (en) 2010-08-17 2023-03-08 3M Innovative Properties Company Lipidated immune response modifier compound and its medical use
US9913469B2 (en) * 2010-08-18 2018-03-13 Monsanto Technology Llc Early applications of encapsulated acetamides for reduced injury in crops
WO2012167088A1 (en) 2011-06-03 2012-12-06 3M Innovative Properties Company Heterobifunctional linkers with polyethylene glycol segments and immune response modifier conjugates made therefrom
EP3366311B1 (en) 2011-06-03 2020-02-26 3M Innovative Properties Co. Hydrazino-1h-imidazoquinolin-4-amines and conjugates made therefrom
EP2729180B1 (en) 2011-07-08 2019-01-23 The University of North Carolina At Chapel Hill Metal bisphosphonate nanoparticles for anti-cancer therapy and imaging and for treating bone disorders
US10517822B2 (en) 2013-11-06 2019-12-31 The University Of Chicago Nanoscale carriers for the delivery or co-delivery of chemotherapeutics, nucleic acids and photosensitizers
US11140900B2 (en) 2014-01-27 2021-10-12 Monsanto Technology Llc Aqueous herbicidal concentrates
US10806694B2 (en) 2014-10-14 2020-10-20 The University Of Chicago Nanoparticles for photodynamic therapy, X-ray induced photodynamic therapy, radiotherapy, radiodynamic therapy, chemotherapy, immunotherapy, and any combination thereof
EP3206987B2 (en) 2014-10-14 2024-07-24 The University of Chicago Nanoparticles for photodynamic therapy, x-ray induced photodynamic therapy, radiotherapy, chemotherapy, immunotherapy, and any combination thereof
EP3291838A4 (en) * 2015-05-05 2019-01-02 B.G. Negev Technologies and Applications Ltd. Anionic nanoparticles for use in the delivery of anionic small molecule drugs
JP7090034B2 (ja) 2016-05-20 2022-06-23 ザ ユニバーシティ オブ シカゴ 化学療法、標的療法、光線力学療法、免疫療法及びそれらの任意の組み合わせのためのナノ粒子
EP3638023A4 (en) 2017-06-13 2021-04-14 Monsanto Technology LLC MICRO ENCAPSULATED HERBICIDES
CN111194232B (zh) 2017-08-02 2023-01-31 芝加哥大学 纳米级金属有机层和金属有机纳米片
CA3086439A1 (en) 2017-12-20 2019-06-27 3M Innovative Properties Company Amide substitued imidazo[4,5-c]quinoline compounds with a branched chain linking group for use as an immune response modifier
EP3917319A4 (en) 2019-01-30 2022-11-23 Monsanto Technology LLC MICRO-ENCAPSULATED ACETAMIDE HERBICIDES

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5948487A (en) * 1997-09-05 1999-09-07 3M Innovative Properties Company Anisotropic retardation layers for display devices

Family Cites Families (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2512572A (en) * 1950-06-20 Substituted pteridines and method
US4030812A (en) * 1975-06-16 1977-06-21 Minnesota Mining And Manufacturing Company Lyotropic birefringent films
US4031092A (en) * 1975-06-16 1977-06-21 Minnesota Mining And Manufacturing Company 1,3-Bis-(carboxy-phenylamino)-s-triazines
IL73534A (en) * 1983-11-18 1990-12-23 Riker Laboratories Inc 1h-imidazo(4,5-c)quinoline-4-amines,their preparation and pharmaceutical compositions containing certain such compounds
US5238944A (en) * 1988-12-15 1993-08-24 Riker Laboratories, Inc. Topical formulations and transdermal delivery systems containing 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine
US5756747A (en) * 1989-02-27 1998-05-26 Riker Laboratories, Inc. 1H-imidazo 4,5-c!quinolin-4-amines
US4929624A (en) * 1989-03-23 1990-05-29 Minnesota Mining And Manufacturing Company Olefinic 1H-imidazo(4,5-c)quinolin-4-amines
US5037986A (en) * 1989-03-23 1991-08-06 Minnesota Mining And Manufacturing Company Olefinic 1H-imidazo[4,5-c]quinolin-4-amines
US4988815A (en) * 1989-10-26 1991-01-29 Riker Laboratories, Inc. 3-Amino or 3-nitro quinoline compounds which are intermediates in preparing 1H-imidazo[4,5-c]quinolines
HU217080B (hu) * 1990-10-05 1999-11-29 Minnesota Mining And Manufacturing Co. Új eljárás imidazo[4,5-c]kinolin-4-amin-származékok előállítására
US5175296A (en) * 1991-03-01 1992-12-29 Minnesota Mining And Manufacturing Company Imidazo[4,5-c]quinolin-4-amines and processes for their preparation
US5389640A (en) * 1991-03-01 1995-02-14 Minnesota Mining And Manufacturing Company 1-substituted, 2-substituted 1H-imidazo[4,5-c]quinolin-4-amines
US5268376A (en) * 1991-09-04 1993-12-07 Minnesota Mining And Manufacturing Company 1-substituted 1H-imidazo[4,5-c]quinolin-4-amines
US5266575A (en) * 1991-11-06 1993-11-30 Minnesota Mining And Manufacturing Company 2-ethyl 1H-imidazo[4,5-ciquinolin-4-amines
DE4211475A1 (de) * 1991-12-14 1993-06-17 Asta Medica Ag Pulverinhalator
US5352461A (en) * 1992-03-11 1994-10-04 Pharmaceutical Discovery Corporation Self assembling diketopiperazine drug delivery system
IL105325A (en) * 1992-04-16 1996-11-14 Minnesota Mining & Mfg Immunogen/vaccine adjuvant composition
US5395937A (en) * 1993-01-29 1995-03-07 Minnesota Mining And Manufacturing Company Process for preparing quinoline amines
EP0708772B1 (en) * 1993-07-15 2000-08-23 Minnesota Mining And Manufacturing Company IMIDAZO [4,5-c]PYRIDIN-4-AMINES
US5352784A (en) * 1993-07-15 1994-10-04 Minnesota Mining And Manufacturing Company Fused cycloalkylimidazopyridines
JP3172190B2 (ja) * 1993-07-15 2001-06-04 ミネソタ マイニング アンド マニュファクチャリング カンパニー 医薬エアロゾルを配給するための器具
US6239116B1 (en) * 1994-07-15 2001-05-29 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US6207646B1 (en) * 1994-07-15 2001-03-27 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
US5482936A (en) * 1995-01-12 1996-01-09 Minnesota Mining And Manufacturing Company Imidazo[4,5-C]quinoline amines
US5693811A (en) * 1996-06-21 1997-12-02 Minnesota Mining And Manufacturing Company Process for preparing tetrahdroimidazoquinolinamines
US5741908A (en) * 1996-06-21 1998-04-21 Minnesota Mining And Manufacturing Company Process for reparing imidazoquinolinamines
ATE283855T1 (de) * 1996-07-03 2004-12-15 Sumitomo Pharma Neue purinderivate
US6387938B1 (en) * 1996-07-05 2002-05-14 Mochida Pharmaceutical Co., Ltd. Benzimidazole derivatives
US6039969A (en) * 1996-10-25 2000-03-21 3M Innovative Properties Company Immune response modifier compounds for treatment of TH2 mediated and related diseases
US5939090A (en) * 1996-12-03 1999-08-17 3M Innovative Properties Company Gel formulations for topical drug delivery
EP0894797A4 (en) * 1997-01-09 2001-08-16 Terumo Corp NEW AMID DERIVATIVES AND INTERMEDIATES ON YOUR SYNTHESIS
US6406705B1 (en) * 1997-03-10 2002-06-18 University Of Iowa Research Foundation Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant
US6248364B1 (en) * 1997-04-07 2001-06-19 3M Innovative Properties Company Encapsulation process and encapsulated products
US6426334B1 (en) * 1997-04-30 2002-07-30 Hybridon, Inc. Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal
DE69838294T2 (de) * 1997-05-20 2009-08-13 Ottawa Health Research Institute, Ottawa Verfahren zur Herstellung von Nukleinsäurekonstrukten
US6329381B1 (en) * 1997-11-28 2001-12-11 Sumitomo Pharmaceuticals Company, Limited Heterocyclic compounds
UA67760C2 (uk) * 1997-12-11 2004-07-15 Міннесота Майнінг Енд Мануфакчурінг Компані Імідазонафтиридин та тетрагідроімідазонафтиридин, фармацевтична композиція, спосіб індукування біосинтезу цитокінів та спосіб лікування вірусної інфекції, проміжні сполуки
TW572758B (en) * 1997-12-22 2004-01-21 Sumitomo Pharma Type 2 helper T cell-selective immune response inhibitors comprising purine derivatives
US6110929A (en) * 1998-07-28 2000-08-29 3M Innovative Properties Company Oxazolo, thiazolo and selenazolo [4,5-c]-quinolin-4-amines and analogs thereof
JP2000119271A (ja) * 1998-08-12 2000-04-25 Hokuriku Seiyaku Co Ltd １ｈ―イミダゾピリジン誘導体
US6180295B1 (en) * 1998-09-11 2001-01-30 Eastman Kodak Company Liquid crystalline filter dyes for imaging elements
US6214499B1 (en) * 1998-09-11 2001-04-10 Eastman Kodak Company Liquid crystalline filter dyes for imaging elements
US6245399B1 (en) * 1998-10-14 2001-06-12 3M Innovative Properties Company Guest-host polarizers
EP1140091B1 (en) * 1999-01-08 2005-09-21 3M Innovative Properties Company Formulations comprising imiquimod or other immune response modifiers for treating cervical dysplasia
US6558951B1 (en) * 1999-02-11 2003-05-06 3M Innovative Properties Company Maturation of dendritic cells with immune response modifying compounds
US6573273B1 (en) * 1999-06-10 2003-06-03 3M Innovative Properties Company Urea substituted imidazoquinolines
US6451810B1 (en) * 1999-06-10 2002-09-17 3M Innovative Properties Company Amide substituted imidazoquinolines
US6331539B1 (en) * 1999-06-10 2001-12-18 3M Innovative Properties Company Sulfonamide and sulfamide substituted imidazoquinolines
US6338443B1 (en) * 1999-06-18 2002-01-15 Mercury Enterprises, Inc. High efficiency medical nebulizer
CA2381993A1 (en) * 1999-08-13 2001-02-22 Hybridon, Inc. Modulation of oligonucleotide cpg-mediated immune stimulation by positional modification of nucleosides
US6538714B1 (en) * 1999-10-25 2003-03-25 3M Innovative Properties Company Dual color guest-host polarizers and devices containing guest-host polarizers
US6574044B1 (en) * 1999-10-25 2003-06-03 3M Innovative Properties Company Polarizer constructions and display devices exhibiting unique color effects
US6376669B1 (en) * 1999-11-05 2002-04-23 3M Innovative Properties Company Dye labeled imidazoquinoline compounds
DE60008137T2 (de) * 1999-11-12 2004-09-16 3M Innovative Properties Co., Saint Paul Flüssigkristallorientierunsstrukturen, verfahren zu deren herstellung und anzeigevorrichtungen, die diese strukturen enthalten
DE10036282A1 (de) * 2000-07-26 2002-02-07 Bosch Gmbh Robert Verfahren und Vorrichtung zur Steuerung einer Antriebseinheit
US20020055517A1 (en) * 2000-09-15 2002-05-09 3M Innovative Properties Company Methods for delaying recurrence of herpes virus symptoms
US6488866B1 (en) * 2000-11-08 2002-12-03 3M Innovative Properties Company Liquid crystal materials and alignment structures and optical devices containing same
US6545016B1 (en) * 2000-12-08 2003-04-08 3M Innovative Properties Company Amide substituted imidazopyridines
US6525064B1 (en) * 2000-12-08 2003-02-25 3M Innovative Properties Company Sulfonamido substituted imidazopyridines
US6545017B1 (en) * 2000-12-08 2003-04-08 3M Innovative Properties Company Urea substituted imidazopyridines
US6411354B1 (en) * 2001-05-11 2002-06-25 Kent State University Bulk alignment of lyotropic chromonic liquid crystals
US6673398B2 (en) * 2001-05-14 2004-01-06 Kent State University Alignment of lyotropic chromonic liquid crystals at surfaces as monolayers and multilayered stacks
BR0214407A (pt) * 2001-11-27 2004-10-19 Anadys Pharmaceuticals Inc Compostos, composições farmacêuticas e método de modulação das imunoatividades da citocina

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5948487A (en) * 1997-09-05 1999-09-07 3M Innovative Properties Company Anisotropic retardation layers for display devices

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7687115B2 (en) 2004-11-24 2010-03-30 3M Innovative Properties Company Method for making nanostructured surfaces
US7582330B2 (en) 2004-11-24 2009-09-01 3M Innovative Properties Counsel Method for making metallic nanostructures
US7718716B2 (en) 2005-10-14 2010-05-18 3M Innovative Properties Company Chromonic nanoparticles containing bioactive compounds
US7629027B2 (en) 2005-10-14 2009-12-08 3M Innovative Properties Company Method for making chromonic nanoparticles
US7807661B2 (en) 2005-12-08 2010-10-05 3M Innovative Properties Company Silver ion releasing articles and methods of manufacture
US7601769B2 (en) 2005-12-19 2009-10-13 3M Innovative Peroperties Company Multilayered chromonic structures
WO2007075282A1 (en) * 2005-12-19 2007-07-05 3M Innovative Properties Company Hierachical chromonic structures
JP2009520026A (ja) * 2005-12-19 2009-05-21 スリーエム イノベイティブ プロパティズ カンパニー 階層的クロモニック構造
US8092710B2 (en) 2005-12-19 2012-01-10 3M Innovative Properties Company Hierarchical chromonic structures
WO2007072083A1 (en) 2005-12-23 2007-06-28 Prosidion Limited Treatment of type 2 diabetes with a combination of dpiv inhibitor and metformin or thiazolidinedione
WO2007079083A1 (en) * 2005-12-28 2007-07-12 3M Innovative Properties Company Encapsulated chromonic particles
US7824732B2 (en) 2005-12-28 2010-11-02 3M Innovative Properties Company Encapsulated chromonic particles
US7981469B2 (en) 2005-12-28 2011-07-19 3M Innovative Properites Company Encapsulated chromonic particles
WO2008060660A3 (en) * 2006-04-13 2008-07-03 3M Innovative Properties Co Method and apparatus for forming crosslinked chromonic nanoparticles
WO2008054866A3 (en) * 2006-05-23 2008-06-19 3M Innovative Properties Co Method of making ordered nanostructured layers

Also Published As

Publication number Publication date
WO2005012488A2 (en) 2005-02-10
RU2006102187A (ru) 2006-08-10
JP2007500712A (ja) 2007-01-18
CA2533128A1 (en) 2005-02-10
JP2007500713A (ja) 2007-01-18
EP1651185A1 (en) 2006-05-03
AU2004261243A1 (en) 2005-02-10
RU2006102188A (ru) 2006-07-10
US20080063714A1 (en) 2008-03-13
US20080039533A1 (en) 2008-02-14
CA2534042A1 (en) 2005-02-10
MXPA06001054A (es) 2006-04-24
KR20060056354A (ko) 2006-05-24
WO2005012488A3 (en) 2005-05-26
IL173301A0 (en) 2006-06-11
EP1651035A2 (en) 2006-05-03
IL173300A0 (en) 2006-06-11
AU2004261987A1 (en) 2005-02-10
MXPA06001004A (es) 2006-04-27
BRPI0413143A (pt) 2006-10-03
KR20060054371A (ko) 2006-05-22
BRPI0413164A (pt) 2006-10-03

Similar Documents

Publication Publication Date Title
US20080039533A1 (en) Bioactive Compositions Comprising Triazines
US7273603B2 (en) HFC solution formulations containing an anticholinergic
EP2574168B9 (en) Topical formulation for a jak inhibitor
US5179079A (en) Nasal formulation and intranasal administration therewith
JP5221343B2 (ja) 担体
EP1891956B1 (en) Solubilization preparation
KR20010042626A (ko) 활성 성분의 흡수 강화를 위한 활성을 갖는 화합물을함유하는 약학적 조성물
KR20130112727A (ko) 향진균성 약학적 조성물
WO2009121039A2 (en) Administration of benzodiazepine compositions
CA2701695A1 (en) Pharmaceutical formulation of valsartan
JP3207212B2 (ja) 吸収促進剤およびこれを含有する外用剤
AU2023201091A1 (en) Cyclodextrin-Panobinostat Adduct
KR20070024543A (ko) 항진균제 전달 방법
JP2006008684A (ja) ジクロフェナクナトリウムとβ−シクロデキストリンとを有する注入可能薬学組成物
JPH06510042A (ja) ロイコトリエンレセプター拮抗剤−抗ヒスタミン剤複合体
KR100866979B1 (ko) 이트라코나졸을 함유한 마이크로이멀젼계 하이드로겔 및이의 제조방법
WO2007147373B1 (en) Pharmaceutical composition for injectional, particularly targeted local administration
KR20060012030A (ko) 디아제팜을 함유하는 경비 마이크로에멀젼
CN1832725A (zh) 含有三嗪的生物活性组合物
CN102079729B (zh) 具有抗寄生虫活性的化合物和含有它们的药物
KR101625926B1 (ko) 포스포디에스터라제 타입-5 억제제의 경피 전달을 향상시키는 방법 및 포스포디에스터라제 타입-5 억제제의 경피 전달을 향상시키는 개선된 약학적 조성물
JP3990728B2 (ja) Ｎ−［４−オキソ−２−（１ｈ−テトラゾール−５−イル）−４ｈ−１−ベンゾピラン−８−イル］−４−（４−フェニルブトキシ）ベンズアミドの塩
JP2010514679A (ja) 制御放出組成物及び方法
JP4895458B2 (ja) 経皮吸収促進剤およびその使用
JP2002538118A (ja) 組成物

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200480022462.8

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2533128

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 10595050

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 2004261243

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2004779530

Country of ref document: EP

Ref document number: PA/a/2006/001054

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 1020067001970

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 545034

Country of ref document: NZ

Ref document number: 2006522067

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 394/CHENP/2006

Country of ref document: IN

ENP Entry into the national phase

Ref document number: 2004261243

Country of ref document: AU

Date of ref document: 20040729

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 2004261243

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2006102188

Country of ref document: RU

WWP Wipo information: published in national office

Ref document number: 2004779530

Country of ref document: EP

ENP Entry into the national phase

Ref document number: PI0413164

Country of ref document: BR