WO2000035298A1 - Chewing-gum contenant des agents medicamenteux actifs - Google Patents

Chewing-gum contenant des agents medicamenteux actifs Download PDF

Info

Publication number
WO2000035298A1
WO2000035298A1 PCT/US1999/029792 US9929792W WO0035298A1 WO 2000035298 A1 WO2000035298 A1 WO 2000035298A1 US 9929792 W US9929792 W US 9929792W WO 0035298 A1 WO0035298 A1 WO 0035298A1
Authority
WO
WIPO (PCT)
Prior art keywords
active agent
coating
gum
chewing gum
active
Prior art date
Application number
PCT/US1999/029792
Other languages
English (en)
Inventor
Gordon N. Mcgrew
David G. Barkalow
Sonya S. Johnson
David W. Record
Mansukh M. Patel
Jack D. Nimz
Steven E. Zibell
Robert J. Yatka
Michael J. Greenberg
Rebecca A. Aumann
Daniel J. Zyck
Daniel J. Sitler
Jeffrey S. Hook
James R. Maxwell
Michael A. Reed
Victor V. Gudas
Philip G. Schnell
Henry T. Tyrpin
Michael P. Russell
David L. Witkewitz
Joo H. Song
Donald J. Townsend
Donald A. Seielstad
Ronald L. Ream
Christine L. Corriveau
William J. Wokas
Thomas M. TONGUE
Original Assignee
Wm. Wrigley Jr. Company
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
Priority claimed from PCT/US1996/018977 external-priority patent/WO1998023165A1/fr
Priority claimed from US09/308,972 external-priority patent/US6165516A/en
Application filed by Wm. Wrigley Jr. Company filed Critical Wm. Wrigley Jr. Company
Priority to BR9916304-7A priority Critical patent/BR9916304A/pt
Priority to EP99966283A priority patent/EP1221863A4/fr
Publication of WO2000035298A1 publication Critical patent/WO2000035298A1/fr
Priority to US09/621,780 priority patent/US6949264B1/en
Priority to US09/714,571 priority patent/US6531114B1/en
Priority to US09/748,699 priority patent/US6541048B2/en
Priority to US10/280,688 priority patent/US20030180414A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/02—Apparatus specially adapted for manufacture or treatment of chewing gum
    • A23G4/025—Apparatus specially adapted for manufacture or treatment of chewing gum for coating or surface-finishing
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A23G4/064—Chewing gum characterised by the composition containing organic or inorganic compounds containing inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A23G4/068—Chewing gum characterised by the composition containing organic or inorganic compounds containing plants or parts thereof, e.g. fruits, seeds, extracts
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A23G4/10—Chewing gum characterised by the composition containing organic or inorganic compounds characterised by the carbohydrates used, e.g. polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/06—Chewing gum characterised by the composition containing organic or inorganic compounds
    • A23G4/12—Chewing gum characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • A23G4/126—Chewing gum characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins containing vitamins, antibiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G4/00—Chewing gum
    • A23G4/18—Chewing gum characterised by shape, structure or physical form, e.g. aerated products
    • A23G4/20—Composite products, e.g. centre-filled, multi-layer, laminated
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/86—Addition of bitterness inhibitors
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • A61K9/0058—Chewing gums
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer

Definitions

  • Patent Application Serial No. 09/389,211 filed September 2, 1999 and a continuation-in-part of U.S. Patent Application Serial No. 09/308,972, filed May 27, 1999, which is a nationalization of PCT/US96/18977, filed November 27, 1996.
  • PCT/US96/18977 filed November 27, 1996.
  • the present invention relates to methods for producing chewing gum. More particularly, the invention relates to producing chewing gum containing an effective amount of an active medicament.
  • the active medicament that is added to the chewing gum has been treated to control its rate of release from chewing gum or the chewing gum formulation has been modified to control the release of medicament for maximum effectiveness.
  • ingredients may require a controlled release from chewing gum.
  • the active medicament that is added to the gum is not generally released very readily.
  • An active medicament may be encapsulated in a water soluble matrix such that, during the chewing period, the medicament may be released quickly, resulting in a fast release. This would allow chewing gum to be a carrier for an active medicament with these fast release characteristics.
  • active medicaments may also have other unpleasant tastes that may be overcome by reducing the release rate of active medicaments from a chewing gum.
  • Another aspect of the present invention contemplates the use of encapsulation techniques.
  • active medicaments may also be unstable in a chewing gum environment.
  • various methods of encapsulation may be needed to improve stability of the active medicament.
  • active medicaments may not be readily released from the chewing gum matrix and their effect may be considerably reduced.
  • a fast release encapsulation may be needed to release active medicament from the gum matrix.
  • medicaments There are a great variety of such medicaments. These medicaments run the gamut from stimulants such as caffeine to drugs such as analgesics, tranquilizers, cardiovascular products, as well as vitamins, minerals, and supplements. Some such medicaments are taken on an "as-needed" basis while other medicaments must be taken at regular intervals by the individual.
  • drugs or medicaments are administered parenterally or enterally.
  • parenteral administration is the administration of the drug intravenously directly into the blood stream.
  • Enteral refers to the administration of the drug into the gastrointestinal tract.
  • the goal of the drug administration is to move the drug from the site of administration towards the systemic circulation.
  • Oral administration of drugs is by far the most common method of moving drugs towards systemic circulation.
  • a further issue affecting the absorption or orally administered drugs is the form of the drug.
  • Most orally administered drugs are in the form of tablets or capsules. This is primarily for convenience, economy, stability, and patient acceptance. Accordingly, these capsules or tablets must be disintegrated or dissolved before absorption can occur. There are a variety of factors capable of varying or retarding disintegration of solid dosage forms. Further, there are a variety of factors that affect the dissolution rate and therefore determine the availability of the drug for absorption. See Merck Manual at page 2600.
  • the drug may be metabolized before it can be measured in the general circulation.
  • This cause of a decrease in drug input is called the first pass effect.
  • a large number of drugs show low bioavailability owning to an extensive first pass metabolism.
  • the two other most frequent causes of low bioavailability are insufficient time in the Gl tract and the presence of competing reactions. See Merck Manual at page 2602.
  • Bioavailability considerations are most often encountered for orally administered drugs. Differences in bioavailability can have profound clinical significance.
  • parenteral administration does provide a method for eliminating a number of the variables that are present with oral administration, parenteral administration is not a preferable route. Typically parenteral administration requires the use of medical personnel and is just not warranted nor practical for the administration of most agents and drugs, e.g., analgesics. Even when required, parenteral administration is not preferred due to patient concerns including comfort, infection, etc., as well as the equipment and costs involved.
  • the present invention provides improved methods for delivering a medicament or active agent to an individual.
  • chewing gum including a medicament or active agent.
  • the medicament or active agent is present within the chewing gum composition (the water soluble portion and/or insoluble base portion). It has been found that by chewing the gum, the medicament or active agent is released from the chewing gum into saliva. Possibly, saliva coats the oral tissues under the tongue (sublingual) and the sides of the mouth where the drug may partition from the saliva into the oral mucosa. Continuing to chew the chewing gum creates a pressure within the buccal cavity and may force the medicament or active agent or medicament directly into the systemic system of the individual through the oral mucosa contained in the buccal cavity. This greatly enhances the absorption of the drug into the systemic system as well as the bioavailability of the drug within the system.
  • the present invention provides a method of drug delivery comprising the steps of: providing a chewing gum that includes a medicament in the chewing gum composition; chewing the chewing gum to cause the medicament to be released from the chewing gum composition into the buccal cavity of the chewer.
  • the active medicament may be any agent that is traditionally used as a medicament and lends itself to being administered through the oral cavity.
  • Such active agents may be vitamins, cancer chemotherapeutics; antimycotics; oral contraceptives, nicotine or nicotine replacement agents, minerals, analgesics, antacids, muscle relaxants, antihistamines, decongestants, antibacterial agents, anesthetics, antitussives, diuretics, anti-inflammatories, antibiotics, AIDS medication, neurological drugs, antivirals, psychotherapeutic agents, anti-diabetic agents and cardiovascular agents, nutraceuticals and nutritional supplements.
  • an advantage of the present invention is to provide new methods for delivering medicaments or active agents to an individual.
  • an advantage of the present invention is to provide a method of delivering medicaments to an individual that provides for increase absorption and bioavailability as compared to medicaments that are designed to be absorbed in the Gl tract. Further, an advantage of the present invention is to provide a method of administering a medicament or agent to an individual at a lower level than is typically administered orally while still achieving the same effect.
  • an advantage of the present invention is to provide a method for administering drugs or agents to an individual that heretofore were administered parenterally.
  • an advantage of the present invention is to provide a method of administering drugs that is more palatable than current methods. Moreover, an advantage of the present invention is to provide an improved method for drug delivery.
  • the present invention also provides a method of producing chewing gum with physically modified active medicaments to control their release. Such active medicaments are added to a gum coating to deliver the active medicaments systemically without unpleasant tastes.
  • the present invention also relates to the chewing gum so produced.
  • Physically modified active medicaments may be added to sucrose-type gum formulations and sucrose- type coatings.
  • the formulation may be a low or high moisture formulation containing low or high amounts of moisture containing syrup.
  • Physically modified active medicaments may also be used in low or non-sugar gum formulations and coatings that use sorbitol, mannitol, other polyols or carbohydrates.
  • Non-sugar formulations may include low or high moisture sugar-free chewing gums.
  • Active medicaments described herein may be combined or co-dried with bulk sweeteners typically used in chewing gum before the active medicaments are physically modified.
  • bulk sweeteners are sucrose, dextrose, fructose and maltodextrins, as well as sugar alcohols such as sorbitol, mannitol, xylitol, maltitol, lactitol, hydrogenated isomaltulose and hydrogenated starch hydrolyzates.
  • the modified release rate noted above may be a fast release or a delayed release.
  • the modified release of active medicaments may be obtained by encapsulation, partial encapsulation or partial coating, entrapment or absorption with high or low water soluble materials or water insoluble materials.
  • the procedures for modifying the active medicaments include spray drying, spray chilling, fluid bed coating, coacervation, extrusion and other agglomerating and standard encapsulating techniques.
  • the active medicaments also may be absorbed onto an inert or water-insoluble material. Active medicaments may be modified in a multiple step process comprising any of the processes, or a combination of the processes noted.
  • active medicaments may also be combined with bulk sweeteners including sucrose, dextrose, fructose, maltodextrin or other bulk sweeteners, as well as sugar alcohols such as sorbitol, mannitol, xylitol, maltitol, lactitol, hydrogenated isomaltulose and hydrogenated starch hydrolyzates.
  • bulk sweeteners including sucrose, dextrose, fructose, maltodextrin or other bulk sweeteners, as well as sugar alcohols such as sorbitol, mannitol, xylitol, maltitol, lactitol, hydrogenated isomaltulose and hydrogenated starch hydrolyzates.
  • active medicaments Prior to encapsulation, active medicaments may be combined with high-intensity sweeteners, including but not limited to thaumatin, aspartame, alitame, acesulfame K, saccharin acid and its salts, glycyrrhizin, cyclamate and its salts, stevioside and dihydrochalcones.
  • high-intensity sweeteners including but not limited to thaumatin, aspartame, alitame, acesulfame K, saccharin acid and its salts, glycyrrhizin, cyclamate and its salts, stevioside and dihydrochalcones.
  • Co-encapsulation of active medicaments along with a high-intensity sweetener may reduce the poor taste qualities of active medicaments and control the sweetener release with active medicaments. This can improve the quality of the gum product and increase consumer acceptability.
  • the present invention provides improved methods for delivering medicaments and other active agents to an individual as well as improved formulations including such medicaments and agents.
  • a physically modified medicament or active is contained in a chewing gum formulation.
  • the medicament or agent is contained directly in the chewing gum composition. Accordingly, as the chewing gum is chewed, the physically modified active is released into the saliva.
  • the medicament or active in the saliva may be then forced due to the pressure created by the chewing gum through the oral mucosa in the buccal cavity. The oral mucosa favors drug absorption.
  • the physically modified active agent and/or medicament remains in the buccal cavity and may be forced or partitioned through the oral mucosa.
  • An increase in the absorption of the drug may be achieved as well as an increase in the bioavailability of the drug as compared to typical oral administration.
  • the drug or active agent may be absorbed much quicker than if it was swallowed as in a typical oral administration. Indeed, the absorption approaches that of a parental administration and bioavailability may be also much greater than oral administration.
  • the administration of the medicament or agent using chewing gum through the buccal activity may provide an increase in therapeutic effect even as compared to parenteral administration.
  • caffeine is commonly used as a stimulant to alleviate the effects of sleep deprivation. It is almost completely metabolized in the liver and therefore classified as a low clearance, flow independent drug. This means its rate of inactivation is unaffected by delivery to the liver and can only be modified by a change in the hepatic enzyme activity.
  • caffeine When caffeine is added to stick chewing gum at a level of about 0.2% to about 5%, caffeine imparts an intense bitterness to the chewing gum that lasts throughout the chewing period. The higher the level used, the stronger the bitterness. At about 0.2%, which is about 5 mg per 2.7 gram stick, the bitterness is below the threshold limit and is not readily discernible.
  • Taste limits in stick chewing gum are generally about 0.4% (10 mg) to about 4% (100 mg) of caffeine in a stick of gum. The 60-80 mg level of caffeine is about the level of caffeine found in a conventional cup of coffee.
  • the target level of caffeine in stick gum is about 40 mg per stick, with a range of about 25-60 mg, so that a five stick package of gum would contain about 200 mg of caffeine, or the equivalent of caffeine in two strong cups of coffee.
  • caffeine bitterness overwhelms the flavor initially and lasts throughout the chewing period.
  • piece weight is generally about 1.5 grams per piece. However, one coated piece of gum is about equal to Vz piece of stick gum. Two pellets are equivalent to a stick of gum, and together weigh about
  • the above-noted target level of 40 mg per stick is equivalent to 20 mg per coated piece, or a range of about 12 to 30 mg caffeine per piece. This is about 0.8% to about 2% caffeine in a piece of coated gum, or a target level of 1.3%.
  • Caffeine is a slightly water soluble substance and, therefore, has a moderately slow release from stick chewing gum. Caffeine is 2.1 % soluble in water at room temperature, 15% soluble in water at 80°C and 40% soluble in boiling water. This gives caffeine a moderately slow release as shown below: Chewing Time % Caffeine Release
  • caffeine Generally, highly water soluble ingredients such as sugars in stick gum are about 80-90% released after only five minutes of chewing. For caffeine, only about 50% is released, while the other 50% remains in the gum after five minutes of chewing. After 20 minutes almost 90% of caffeine is released. Even if caffeine is dissolved in hot water and mixed in the stick gum, when the gum is cooled or kept at room temperature, caffeine may return to its normal crystalline state and release at a rate similar to that shown above. When a physically modified active such as caffeine is added to a gum stick, the active agent will have an increased water solubility, and release quickly into the mouth from the gum.
  • active agent which may generally be non-water soluble
  • physically modifying the active agent by various forms at encapsulation will increase the release of the active agent from chewing gum.
  • Most water soluble active agents can be modified by encapsulation to give a more uniform release from chewing gum.
  • the level released from the gum into the mouth can be adjusted for maximum effectiveness.
  • Other agents or medicaments may be included in the present invention.
  • active agent the present invention refers to a compound that has a desired therapeutic or physiological effect once ingested and/or metabolized.
  • the therapeutic effect may be one which decreases the growth of a xenobiotic or other gut flora or fauna, alters the activity of an enzyme, provides the physical relief from a malady (e.g., diminishes pain, acid reflux or other discomfort), has an effect on the brain chemistry of molecules that determine mood and behavior.
  • a malady e.g., diminishes pain, acid reflux or other discomfort
  • a particular agent has or is associated with a given therapeutic effect.
  • the active agent may be any agent that is traditionally used as a medicament and lends itself to being administered through the oral cavity.
  • Such active agents may be vitamins, cancer chemotherapeutics; antimycotics; oral contraceptives, nicotine or nicotine replacement agents, minerals, analgesics, antacids, muscle relaxants, antihistamines, decongestants, anesthetics, antitussives, diuretics, anti-inflammatories, antibiotics, antivirals, psychotherapeutic agents, anti-diabetic agents and cardiovascular agents, bioengineered pharmaceuticals, nutraceuticals and nutritional supplements.
  • Vitamins and co-enzymes that may be delivered using this invention include but are not limited to water or fat soluble vitamins such as thiamin, riboflavin, nicotinic acid, pyridoxine, pantothenic acid, biotin, flavin, choline, inositol and paraminobenzoic acid, carnitine, vitamin C, vitamin D and its analogs, vitamin A and the carotenoids, retinoic acid, vitamin E and vitamin K.
  • water or fat soluble vitamins such as thiamin, riboflavin, nicotinic acid, pyridoxine, pantothenic acid, biotin, flavin, choline, inositol and paraminobenzoic acid, carnitine, vitamin C, vitamin D and its analogs, vitamin A and the carotenoids, retinoic acid, vitamin E and vitamin K.
  • cancer chemotherapeutics agents include but are not limited to cisplatin (CDDP), procarbazine, mechlorethamine, cyclophosphamide, ,camptothecin, ifosfamide, melphalan, chlorambucil, bisulfan, nitrosurea, dactinomycin: daunorubicin, doxorubicin, bleomycin, plicomycin, mitomycin, etoposide (VP16), tamoxifen, taxol, transplatinum, 5-fluorouracil, vincristin, vinblastin and methotrexate or any analog or derivative variant thereof.
  • CDDP cisplatin
  • procarbazine mechlorethamine
  • cyclophosphamide cyclophosphamide
  • camptothecin ifosfamide
  • melphalan chlorambucil
  • bisulfan nitrosurea
  • dactinomycin daunorubi
  • Antimicrobial agents that may be used include but are not limited to naficillin, oxacillin, vancomycin, clindamycin, erythromycin, trimethoprim-sulphamethoxazole, rifampin, ciprofloxacin, broad spectrum penicillin, amoxicillin, gentamicin, ceftriazoxone, cefotaxime, chloramphenicol, clavunate, sulbactam, probenecid, doxycycline, spectinomycin, cefixime, penicillin G, minocycline, P-lactamase inhibitors; meziocillin, piperacillin, aztreonam, norfloxacin, trimethoprim, ceftazidime, dapsone.
  • Antifungal agents that may be delivered include but are not limited to ketoconazole, fluconazole, nystatin, itraconazole, clomitrazole, and amphotericin B.
  • Antiviral agents that may be used include but are not limited to acyclovir, trifluridine, idoxorudine, foscamet, ganciclovir, zidovudine, dideoxycytosine, dideoxyinosine, stavudine, famciclovir, didanosine, zalcitabine, rifimantadine, and cytokines.
  • Antacids include cimetidine, ranitidine, nizatidine, famotidine, omeprazole, bismuth antacids, metronidazole antacids, tetracylcine antacids, clarthromycin antacids, hydroxides of aluminum, magnesium, sodium bicarbonates, calcium bicarbonate and other carbonates, silicates, and phosphates.
  • Antihistamines are represented by but are not limited to cimetidine, ranitidine, diphenydramine, prylamine, promethazine, chlorpheniramine, chlorcyclizine, terfenadine, carbinoxamine maleate, clemastine fumarate, diphenhydramine hydrochloride, dimenhydrinate, prilamine maleate, tripelennamine hydrochloride, tripelennamine citrate, chlorpheniramine maleate, brompheniramine maleate, hydroxyzine pamoate, hydroxyzine hydrochloride, cyclizine lactate, cyclizine hydrochloride, meclizine hydrochloride, acrivastine, cetirizine hydrochloride, astemizole, levocabastine hydrochloride, and loratadine.
  • Decongestants and antitussives include agents such as dextromethorphan hydrobromide, levopropoxyphene napsylate, noscapine, carbetapentane, caramiphen, chlophedianol, pseudoephedrine hydrochloride, pseudoephedrine sulfate, phenylephidrine, diphenhydramine, glaucine, pholcodine, and benzonatate.
  • Anesthetics include etomidate, ketamine, propofol, and benodiazapines (e.g., chlordiazepoxide, diazepame, clorezepate, halazepam, flurazepam, quazepam, estazolam, triazolam, alprozolm, midazolam, temazepam, oxazepam, lorazepam), benzocaine, dyclonine, bupivacaine, etidocaine, lidocaine, mepivacaine, promoxine, prilocaine, procaine, proparcaine, ropivacaine, tetracaine.
  • benodiazapines e.g., chlordiazepoxide, diazepame, clorezepate, halazepam, flurazepam, quazepam, estazolam, triazolam, alprozolm, mida
  • Other useful agents may include amobartital, aprobarbital, butabarbital, butalbital mephobarbital, methohexital, pentobarbital, phenobarbital, secobarbital, thiopental, paral, chloralhydrate, ethchlorvynol, clutethimide, methprylon, ethinamate, and meprobamate.
  • Analgesics include opioids and other medicaments such as morphine, mepidine, dentanyl, sufentranil, alfentanil, aspirin, acetaminophen, ibuprofen, indomethacine, naproxen, atrin, isocome, midrin, axotal, firinal, phrenilin, ergot, and ergot derivatives (wigraine, cafergot, ergostat, ergomar, dihydroergotamine), imitrex, and ketoprofen.
  • opioids include opioids and other medicaments such as morphine, mepidine, dentanyl, sufentranil, alfentanil, aspirin, acetaminophen, ibuprofen, indomethacine, naproxen, atrin, isocome, midrin, axotal, firinal, phrenilin, ergot, and ergot derivatives (wigraine,
  • Diuretics include but are not limited to acetazolamide, dichlorphenamide, methazolamide, furosemide, bumetanide, ethacrynic acid torseimde, azosemide, muzolimine, piretanide, tripamide, bendroflumethiazide, benzthiazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, trichlormethiazide, indapamide, metolazone, quinethazone, amiloride, triamterene, sprion olactone, canrenone, and potassium canrenoate.
  • Anti-inflammatories include but are not limited to salicylic acid derivatives (e.g. aspirin), indole and indene acetic acids (indomethacin, sulindac and etodalac) heteroaryl acetic acids (tolmetin diclofenac and ketorolac) aryl propionic acid derivatives (ibuprofen, naproxen, ketoprofen, fenopren, oxaprozine), anthranilic acids (mefenamic acid, meclofenamic acid) enolic acids (piroxicam, tenoxicam, phenylbutazone and oxyphenthatrazone).
  • salicylic acid derivatives e.g. aspirin
  • indole and indene acetic acids indomethacin, sulindac and etodalac
  • heteroaryl acetic acids tolmetin diclofenac and ketorolac
  • Psychotherapeutic agents include thorazine, serentil, mellaril, millazinetindal, permitil, prolixin, trilafon, stelazine, suprazine, taractan, navan, clozaril, haldol, halperon, loxitane, moban, orap, risperdal, aiprazolam, chordiaepoxide, clonezepam, clorezepate, diazepam, halazepam, lorazepam, oxazepam, prazepam, buspirone, elvavil, anafranil, adapin, sinequan, tofranil, surmontil, asendin, norpramin, pertofrane, ludiomil, pamelor, vivactil, prozac, luvox, paxil, zoloft, effexor, wellbutrin, serzone, desy
  • Cardiovascular agents include but are not limited to nitroglycerin, isosorbide dinitrate, sodium nitroprisside, captopril, enalaprill, enalaprilat, quinapril, lisinopril, ramipril, losartan, amrinone, linnone, vesnerinone, hydralazine, nicorandil, prozasin, doxazosin, bunazosin, tamulosin, yohimbine, propanolol, metoprolol, nadolol, atenolol, timolol, esmolol, pindolol, acebutolol, labetalol, phentolamine, carvedilol, bucindolol, verapamil, nifedipine, amlodipine and dobutamine, or a sexual dysfunction agent like sildenafil citrate (
  • the resultant chewing gum can be used to treat inter alia: coughs, colds, motion sickness; allergies; fevers; pain; inflammation; sore throats; cold sores; migraines; sinus problems; diarrhea; diabetes, gastritis; depression; anxiety, hypertension; angina and other maladies and symptoms. Also these gums may be useful in ameliorating cravings in substance abuse withdrawal or for appetite suppression.
  • Specific active agents or medicaments include by way of example and limitation: caffeine, aspirin, acetaminophen; ibuprofen; ketoprofen; cimetidine, ranitidine, famotidine, dramamine, omeprazole, dyclonine hydrochloride, chlorpheniramine maleate, pseudoephedrine hydrochloride, dextromethorphan hydrobromide, benzocaine, sodium naproxen, and nicotine.
  • compositions that may be formulated into a suitable chewing gum formulation are described in, for examples, U.S. Patent No. 5,858,423; U.S. Patent No. 5,858,413; U.S. Patent No. 5,858,412 and U.S. Patent No. 5,858,383. Additionally, Goodman and Gilman's "The Pharmaceutical
  • Nutraceuticals and nutritional supplements may also be added to chewing gums as active agents.
  • herbs and botanicals that include, but are not limited to capsicum, chamomile, cat's claw, echinacea, garlic, ginger, ginko, various ginseng, green tea, golden seal, kava kava, nettle, passion flower, saw palmetto, St. John's wort, and valerian.
  • mineral supplements such as calcium, copper, iodine, iron, magnesium, manganese, molybdenum, phosphorous, selenium and zinc.
  • nutraceuticals that also can be added to chewing gum as active agents are benzoin, fructo-oligosaccharides, glucosamine, grapeseed extract, guarana, inulin, phosphotidylserine, phytosterols, phytochemicals, isoflavones, lecithin, lycopene, oligofructose, polyphenol and psyllium as well as weight loss agents such as chromium picolinate and phenylpropanolamine.
  • the agents or medicaments are contained in the chewing gum formulation at levels of approximately 50 micrograms to 500 milligrams.
  • the specific levels will depend on the active ingredient. For example, if chromium picolinate is the active ingredient in an embodiment, it would be present at a level of 50 micrograms per serving (2.8 grams stick of gum); aspirin would be preset at a level of 325 milligrams per 2.8/gram serving (stick).
  • the level of medicament or agent in the chewing gum formulation is selected so as to create, when the gum is chewed, a sufficiently high concentration of the medicament or agent in the saliva.
  • the level of the stimulant in the chewing gum should be such that it creates a saliva content of stimulant of approximately 15 to 440 ppm when the chewing gum is chewed for 2 minutes. At this level, a sufficient amount of stimulant will be delivered to the chewer to create the effects set forth in the application. If a medicament is used such as a medicinal agent (e.g., analgesics), sufficient medicinal agent should be present in the chewing gum to create a salvia content of approximately 1700 to approximately 4400 ppm after the chewing gum has been chewed for 2 minutes.
  • a medicament such as a medicinal agent (e.g., analgesics)
  • sufficient medicinal agent should be present in the chewing gum to create a salvia content of approximately 1700 to approximately 4400 ppm after the chewing gum has been chewed for 2 minutes.
  • the agent should be present in a sufficient amount to create a saliva content of approximately 85 to 1100 ppm when the chewing gum is chewed for 2 minutes.
  • a metabolizer for example, chromium picolinate and hydroxi-chitic acid
  • the agents should be present in an amount to create a saliva content of approximately 0.5 to about 900 ppm when chewed for at least two minutes.
  • the agent is a vitamin or mineral (e.g., phosphatidy serine, vitamin C, and zinc)
  • the agent should be present in the amount to create a saliva content of the vitamin or mineral of approximately 10 to about 250 ppm when chewed for 2 minutes.
  • the dosing regiment will change. For example, if the medicament is an analgesic, the chewing gum would be taken on an as needed basis.
  • the number of pieces of chewing gum chewed for example, not more often than one stick every four hours and not more often than four to five times a day.
  • the agent is a stimulant such as caffeine to be used to enhance performance than the chewing gum would be chewed, in a preferred embodiment ten minutes or less before the performance.
  • the medicament or agent can be contained in a variety of different chewing gum compositions.
  • the chewing gum including the medicament or agent may be based on a variety of different chewing gums that are known.
  • the chewing gums can be low or high moisture, sugar or sugarless, wax containing or wax free, low calorie (via high base or low calorie bulking agents), and/or may contain dental agents.
  • the active agent may also be encapsulated or entrapped to give a delayed release from stick chewing gum and from a gum coating.
  • Any standard technique which gives partial or full encapsulation of the active agent can be used. These techniques include, but are not limited to, spray drying, spray chilling, fluid-bed coating and coacervation. These encapsulation techniques may be used individually in a single step process or in any combination in a multiple step process.
  • Active agents may be encapsulated with sweeteners, more specifically high-intensity sweeteners such as thaumatin, dihydrochalcones, acesulfame
  • K aspartame, N-substituted APM derivatives such as neotame, sucralose, alitame, saccharin and cyclamates. These can also have the effect of reducing unpleasant tastes such as bitterness. Additional bitterness inhibitors or taste maskers can also be combined with active agents and sweeteners to give a reduced unpleasant taste such as bitterness with delayed release active agent(s).
  • compositions that have high organic solubility, good film-forming properties and low water solubility give better delayed release of active agents such as caffeine, while compositions that have high water solubility give better fast release.
  • low water-solubility compositions include acrylic polymers and copolymers, carboxyvinyl polymer, polyamides, polystyrene, polyvinyl acetate, polyvinyl acetate phthalate, polyvinylpyrrolidone and waxes.
  • encapsulants like acacia or maltodextrin can also encapsulate active agent(s) and give a fast release rate in gum.
  • the amount of coating or encapsulating material on the active agent also may control the length of time for its release from chewing gum. Generally, the higher the level of coating and the lower the amount of active agent, the slower the release during mastication with low water soluble compositions.
  • the release rate is generally not instantaneous, but gradual over an extended period of time for stick gum. Delayed release allows the active agent to be masked in the mouth before being ingested, thus reducing bitterness or other unpleasant tastes.
  • the encapsulant should be a minimum of about 20% of the coated active.
  • the encapsulant should be a minimum of about 30% of the coated active, and most preferably should be a minimum of about 40% of the coated active.
  • water soluble encapsulating agents will increase the release rate of water insoluble active agents.
  • Another method of giving a modified release of active agent and the other agents described herein is agglomeration with an agglomerating agent which partially coats the active agents.
  • This method includes the step of mixing active agents and an agglomerating agent with a small amount of water or solvent. The mixture is prepared in such a way as to have individual wet particles in contact with each other so that a partial coating can be applied. After the water or other solvent is removed, the mixture is ground and used as a powdered active agent.
  • agglomerating agent Materials that can be used as the agglomerating agent are the same as those used in encapsulation mentioned previously. Some of the better agglomerating agents for delayed release are the organic polymers like acrylic polymers and copolymers, polyvinyl acetate, polyvinylpyrrolidone, waxes, shellac and Zein. Other agglomerating agents are not as effective in giving a delayed release as are the polymers, waxes, shellac and Zein, but can be used to give some delayed release.
  • agglomerating agents include, but are not limited to, agar, alginates, a wide range of water soluble cellulose derivatives like ethyl cellulose, methyl cellulose, sodium hydroxymethyl cellulose, hydroxypropylmethyl cellulose, dextrin, gelatin, modified starches, and vegetable gums like guar gum, locust bean gum and carrageenan.
  • the level of coating used in the agglomerated product is a minimum of about 5%.
  • the coating level is a minimum of about 15% and more preferably about 20%.
  • a higher or lower amount of agent may be needed to give the desired release of the active agent.
  • water soluble agglomerants will increase the rate of release of water insoluble active agents.
  • Active agents may be coated in a two-step process or a multiple step process. Active agents may be encapsulated with any of the materials as described previously and then the encapsulated caffeine or other active agents can be agglomerated as previously described to obtain an encapsulated/agglomerated active agent product that could be used in chewing gum to give a delayed release of the active agent. In another embodiment of this invention, active agent may be absorbed onto another component which is porous and becomes entrapped in the matrix of the porous component.
  • Common materials used for absorbing active agents include, but are not limited to, silicas, silicates, pharmasorb clay, sponge-like beads or microbeads, amorphous carbonates and hydroxides, including aluminum and calcium lakes, all of which result in a delayed release of caffeine or other active agent.
  • the amount of active agent that can be loaded onto the absorbent will vary.
  • materials like polymers or sponge-like beads or microbeads, amorphous sugars and alditols and amorphous carbonates and hydroxides absorb about 10% to about 40% of the weight of the absorbent.
  • Other materials like silicas and pharmasorb clays may be able to absorb about 20% to about 80% of the weight of the absorbent.
  • water soluble absorbants will increase the release rate of water insoluble active agents.
  • the general procedure for absorbing active agent onto the absorbent is as follows.
  • An absorbent like fumed silica powder can be mixed in a powder blender and a solution of active agent can be sprayed onto the powder as mixing continues.
  • the aqueous solution can be about 1 to 2% solids, and higher solid levels to 15-30% may be used if temperatures up to 90°C are used.
  • water is the solvent, but other solvents like alcohol could also be used if approved.
  • the powder mixes the liquid is sprayed onto the powder. Spraying is stopped before the mix becomes damp.
  • the still free-flowing powder is removed from the mixer and dried to remove the water or other solvent, and is then ground to a specific particle size.
  • the fixative/active agent can be coated by encapsulation.
  • Either full or partial encapsulation may be used, depending on the coating composition used in the process.
  • Full encapsulation may be obtained by coating with a polymer as in spray drying, spray chilling, fluid-bed coating, coapervation, or any other standard technique.
  • a partial encapsulation or coating can be obtained by agglomeration of the fixative/active agent mixture using any of the materials discussed above.
  • Another form of encapsulation is by entrapment of an ingredient by fiber extrusion or fiber spinning into a polymer.
  • Polymers that can be used for extrusion are PVAC, hydroxypropyl cellulose, polyethylene and other types of plastic polymers.
  • a process of encapsulation by fiber extrusion is disclosed in
  • the water insoluble polymer may be preblended with caffeine or other active agents prior to fiber extrusion, or may be added after the polymer is melted. As the extrudate is extruded, it results in small fibers that are cooled and ground. This type of encapsulation/entrapment generally gives a very long, delayed release of an active ingredient.
  • the four primary methods to obtain a treated active agent are:
  • Medicament actives may be combined in a chewing gum.
  • two, three, or more actives may be added to a single piece.
  • One active could be encapsulated for fast release, another active for moderate release, and another active for slow release.
  • a single medicament active could be encapsulated and entrapped to release at various times as the gum is being chewed. This type of gum formulation could be effective for time release medication.
  • Medicament actives may also be combined in a coated chewing gum product.
  • a single active may be added to a gum coating for fast release and also added to the gum center with or without encapsulation for slow release. If the active has an affinity for the gum base it may naturally give a slow release without encapsulation. If the active is fast release it would have to be encapsulated or entrapped for the desired time release.
  • a combination of medicament actives may be used in the gum coating and in the gum center for various reasons.
  • medicaments may be reactive to one another and should be kept from coming in contact with each other.
  • combinations of medicaments may be used for various symptoms where multiple medicaments may be effective.
  • a decongestant such as pseudoephedrine may be added to a gum coating and an antihistamine such as chloropheniramine may be added to a gum center to treat cold/allergy symptoms.
  • an oral anesthetic like dyclonine hydrochloride may be used in the gum coating and an antibacterial agent like cetyl pyridinium chloride may be added to a gum center.
  • any other materials like dextromethorphan hydrobromide for cough relief or an analgesic like ketoprofen may be added to either a gum coating and a gum center for cold symptoms.
  • Other combinations of medicament active agents for other types of ailments are also within the scope of this invention.
  • a medicament may have a bitter taste. If the medicament were added to a coating at a very low level, it would still have the effect of fast release initially.
  • the active agent may be added to the gum coating at a very low level beneath its taste threshold. Additional active agent that is encapsulated and entrapped may then be added to the gum center for slow release. This bitter active agent can then be kept below its taste threshold level and release slowly as the gum is being chewed, but the active agent would continue to be released to give its effective dosage.
  • active medicaments may have a low quality off- taste or bitterness, especially if added to a chewing gum coating. In most cases, this off taste may be masked with high intensity sweeteners, but in other instances, a bitterness inhibitor may be needed to reduce a bitter taste of a medicament.
  • bitterness inhibitors there are a wide variety of bitterness inhibitors that can be used in food products as well as with active agents. Some of the preferred bitterness inhibitors are the sodium salts which are discussed in the article Suppression of Bitterness by Sodium: Variations Among Bitter Taste Stimuli, by R.A.S.
  • Sodium salts discussed are sodium acetate and sodium gluconate. Other sodium salts that may also be effective are sodium glycinate, sodium ascorbate and sodium glycerolphosphate. Among these, the most preferred is sodium gluconate and sodium glycinate since they have a low salty taste and are most effective to reduce bitterness of most active medicaments. Most of the sodium salts are very water soluble and are readily released from chewing gum to function as bitterness inhibitors. In most instances, the sodium salts which release readily from chewing gum may be modified by encapsulation to give an even faster release from chewing gum. However, in some instances the sodium salts would be encapsulated or entrapped to give a delayed release from gum. Generally, the bitterness inhibitor should release with the active medicament for maximum effectiveness.
  • medicaments may be dissolved in solvents, flavors, or other transdermal vehicles used as absorption enhancing agents and added to gum or to a gum coating.
  • the absorption enhancing agents may also be added to the gum or gum coating separately from the active ingredient. Their presence may help volatilize medicaments or allow increased buccal/lingual absorption of the active agent through the nasal mucosal or the lungs.
  • solvents, flavors, or transdermal vehicles may transport medicaments faster through the oral mucosa.
  • Faster absorption may be affected by increasing flavor levels as well as the addition of other flavor components, such as menthol and menthol derivatives, limonene, carvone, isomenthol, eucalyptol, menthone, pynene, camphor and camphor derivatives, as well as monoterpene natural products, monoterpene derivatives, and sesquaterpenes, including caryophyllene and copaene.
  • other flavor components such as menthol and menthol derivatives, limonene, carvone, isomenthol, eucalyptol, menthone, pynene, camphor and camphor derivatives, as well as monoterpene natural products, monoterpene derivatives, and sesquaterpenes, including caryophyllene and copaene.
  • ethanol polyethylene glycol
  • 2-pyrrolidones myristic acid
  • Brij-35 surfactant
  • p-phenyl phenol nitrobenzene
  • stearyl alcohol cetyl alcohol
  • croton oil liquid paraffin
  • dimethyl sulfoxide (DMSO) non-ionic surfactants
  • liposomes lecithin fractions
  • long chain amphipathic molecules molecules with polar or non-ionized groups on one end and non- polar groups at the other end.
  • polysaccharides such as cellulose gums, natural gums like guar gum, gum arabic, and others may be mixed with active medicaments or mixed in the gum formulation with the medicament. This may allow the medicaments to stick to the surface of the oral mucosa during chewing and increase oral absorption. Bioadhesives may act in a similar manner to achieve increased absorption of the active medicament.
  • the gum formulation may have an effect on release rate of the medicament.
  • Water miscible medicaments may be released more slowly when using a highly hydrophillic gum base and more quickly from a lipophillic gum base.
  • oil miscible medicaments may release more quickly when using a highly hydrophillic gum base and more slowly from a lipophillic gum base.
  • medicaments may release more quickly by using high HLB solubilizers in the gum formulation.
  • Medicaments may also be emulsified together with water soluble bulking agents to increase release of the medicaments.
  • gum formula modifications may also affect the release rate of medicaments. Texture modifiers to soften base may give faster release where hard bases may give slower release. Addition of alkaline materials such as sodium bicarbonate or sodium hydroxide may make the saliva slightly alkaline, which may increase buccal/lingual absorption of the medicament into the bloodstream. Use of a buffer in the gum formula may affect release rate or absorption or shelf life of certain medicaments or supplements. Gum base made with talc may offer unique release and shelf life improvements. Other additives, such as astringents may give the sensation of dry mouth, which may improve medicament absorption. Also, some types of hot, spicy flavors such as ginger or hot pepper may give the impression of high activity of the medicament.
  • Medicaments may be added to chewing gum via special carriers which may affect the release rate and its absorption. Some carriers that may be used are activated charcoal, molecular sieves, corn starch granules, microsponges, or liposomes.
  • the medicament may be sugar or polyol candy coated, or entrapped in cyclodextrin for fast release to dissolve quickly in the mouth during chewing.
  • Release of the medicament from gum may also be effected by particle size of the coated medicament. Small particles release more quickly whereas large particles more slowly.
  • Fast release can also be accomplished by dissolving medicament in a liquid and used in a liquid center gum.
  • Some medicaments may be advantageous to use in both slow and fast release. Quick release may give good oral absorption, then slow release may result by swallowing the cud. This may be particularly effective if a biodegradable gum base is used.
  • some medicaments may have an advantage with a slow initial release, but increases later. This can reduce side effects of the medicament and improve adaptation to the medicament. Slow release may also be accomplished by attaching a medicament to a polymer used in the chewing gum.
  • Release of a medicament or active agent may also be effected by the shape and size of the chewing gum product.
  • Flat stick pieces of gum with large surface area may release actives faster into saliva from gum when chewed, whereas round or cube pieces may release medicaments and actives more slowly.
  • Gum formulations, especially those that are anhydrous or have no gum softening agents may be ground to a powder. This powder may be dusted onto the surface of another gum formulation or coated onto a ball or pillow shape gum product. This powder may also be tabletted in a tablet press to give a unique form to be chewed for release of its active agent. Other forms of gum to be used are rolled sticks, or soft squeezable gum from a tube.
  • Active medicaments can also be added to chewing gum formulations that are made into tablets. Tableting of chewing gum is disclosed in U.K. Patent Publication No. 1 ,489,832; U.S. Patent No. 4,753,805; EP Patent Publication No. 0 221 850; and Italy Patent Publication No. 1 ,273,487. These patents disclose active agents added to chewing gum which is then tableted. As an embodiment of this invention, active agents may be encapsulated or entrapped and added to a chewing gum formulation which is then tableted. In addition, a formed chewing gum tablet may also be used as a core for a coated chewing gum pellet that is coated with a sugar, polyol or film. The chewing gum core may contain one active agent or multiple active medicaments and the coating may contain one or more active medicaments. This form will yield unique chewing gum products.
  • a chewing gum composition typically comprises a water-soluble bulk portion, a water-insoluble chewable grams base portion and typically water-insoluble flavoring agents. The water-soluble portion dissipates with a portion of the flavoring agent over a period of time during chewing. The gum base portion is retained in the mouth throughout the chew.
  • the insoluble gum base generally comprises elastomers, resins, fats and oils, softeners and inorganic fillers.
  • the gum base may or may not include wax.
  • the insoluble gum base can constitute approximately 5% to about 95% by weight of the chewing gum, more commonly the gum base comprises 10% to about 50% of the gum, and in some preferred embodiments approximately 25% to about 35% by weight, of the chewing gum.
  • the chewing gum base of the present invention contains about 20% to about 60% by weight synthetic elastomer, about 0% to about 30% by weight natural elastomer, about 5% to about 55% by weight elastomer plasticizer, about 4% to about 35% by weight filler, about
  • softener 5% to about 35% by weight softener, and optional minor amounts (about 1% or less by weight) of miscellaneous ingredients such as colorants, antioxidants, etc.
  • Synthetic elastomers may include, but are not limited to, polyisobutylene with GPC weight average molecular weight of about 10,000 to about 95,000, isobutylene-isoprene copolymer (butyl elastomer), styrene-butadiene, copolymers having styrene-butadiene ratios of about 1 :3 to about 3: 1 , polyvinyl acetate having GPC weight average molecular weight of about 2,000 to about 90,000, polyisoprene, polyethylene, vinyl acetate - vinyl laurate copolymer having vinyl laurate content of about 5% to about 50% by weight of the copolymer, and combinations thereof.
  • Preferred ranges for polyisobutylene are 50,000 to 80,000 GPC weight average molecular weight and for styrene-butadiene are 1 : 1 to 1 :3 bound styrene-butadiene, for polyvinyl acetate are 10,000 to 65,000 GBC weight average molecular weight with the higher molecular weight polyvinyl acetates typically used in bubble gum base, and for vinyl acetate-vinyl laurate, vinyl laurate content of 10-45%.
  • Natural elastomers may include natural rubber such as smoked or liquid latex and guayule as well as natural gums such as jelutong, lechi caspi, perillo, sorva, massaranduba balata, massaranduba chocolate, nispero, rosindinha, chicle, gutta hang kang, and combinations thereof.
  • the preferred synthetic elastomer and natural elastomer concentrations vary depending on whether the chewing gum in which the base is used is adhesive or conventional, bubble gum or regular gum, as discussed below.
  • Preferred natural elastomers include jelutong, chicle, sorva and massaranduba balata.
  • Elastomer plasticizers may include, but are not limited to, natural rosin esters such as glycerol esters or partially hydrogenated rosin, glycerol esters of polymerized rosin, glycerol esters of partially dimerized rosin, glycerol esters of rosin, pentaerythritol esters of partially hydrogenated rosin, methyl and partially hydrogenated methyl esters of rosin, pentaerythritol esters of rosin; synthetics such as terpene resins derived from alpha-pinene, beta-pinene, and/or d-limonene; and any suitable combinations of the foregoing.
  • the preferred elastomer plasticizers will also vary depending on the specific application, and on the type of elastomer which is used.
  • Fillers/texturizers may include magnesium and calcium carbonate, ground limestone, silicate types such as magnesium and aluminum silicate, clay, alumina, talc, titanium oxide, mono-, di- and tri-calcium phosphate, cellulose polymers, such as wood, and combinations thereof.
  • Softeners/emulsifiers may include tallow, hydrogenated tallow, hydrogenated and partially hydrogenated vegetable oils, cocoa butter, glycerol monostearate, glycerol triacetate, lecithin, mono-,.di- and triglycerides, acetylated monoglycerides, fatty acids (e.g. stearic, palmitic, oleic and linoleic acids), and combinations thereof
  • Colorants and whiteners may include FD&C-type dyes and lakes, fruit and vegetable extracts, titanium dioxide, and combinations thereof.
  • the base may or may not include wax.
  • An example of a wax-free gum base is disclosed in U.S. Patent No. 5,286,500, the disclosure of which is incorporated herein by reference.
  • a typical chewing gum composition includes a water soluble bulk portion and one or more flavoring agents.
  • the water soluble portion can include bulk sweeteners, high intensity sweeteners, flavoring agents, softeners, emulsifiers, colors, acidulants, fillers, antioxidants, and other components that provide desired attributes.
  • Softeners are added to the chewing gum in order to optimize the chewability and mouth feel of the gum.
  • the softeners which are also known as plasticizers and plasticizing agents, generally constitute between approximately 0.5% to about 15% by weight of the chewing gum.
  • the softeners may include glycerin, lecithin, and combinations thereof.
  • Aqueous sweetener solutions such as those containing sorbitol, hydrogenated starch hydrolysates, corn syrup and combinations thereof, may also be used as softeners and binding agents in chewing gum.
  • Bulk sweeteners include both sugar and sugarless components. Bulk sweeteners typically constitute about 5% to about 95% by weight of the chewing gum, more typically, about 20% to about 80% by weight, and more commonly, about 30% to about 60% by weight of the gum.
  • Sugar sweeteners generally include saccharide-containing components commonly known in the chewing gum art, including but not limited to, sucrose, dextrose, maltose, dextrin, dried invert sugar, fructose, levulose, glactose, corn syrup solids, and the like, alone or in combination.
  • Sugarless sweeteners include, but are not limited to, sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates, maltitol, and the like, alone or in combination.
  • High intensity artificial sweeteners can also be used, alone or in combination, with the above.
  • Preferred sweeteners include, but are not limited to, sucralose, aspartame, N-substituted APM derivatives such as neotame, salts of acesulfame, altitame, saccharin and its salts, cyclamic acid and its salts, glycyrrhizinate, dihydrochalcones, thaumatin, monellin, and the like, alone or in combination.
  • Such techniques as wet granulation, wax granulation, spray drying, spray chilling, fluid bed coating, coacervation, and fiber extension may be used to achieve the desired release characteristics.
  • Combinations of sugar and/or sugarless sweeteners may be used in chewing gum. Additionally, the softener may also provide additional sweetness such as with aqueous sugar or alditol solutions.
  • a low caloric bulking agent can be used.
  • low caloric bulking agents include: polydextrose; Raftilose, Raftilin; Fructooligosaccharides (NutraFlora); Palatinose oligosaccharide; Guar Gum Hydrolysate (Sun Fiber); or indigestible dextrin (Fibersol).
  • flavoring agents can also be used, if desired.
  • the flavor can be used in amounts of about 0. 1 to about 15 weight percent of the gum, and preferably, about 0.2% to about 5% by weight.
  • Flavoring agents may include essential oils, synthetic flavors or mixtures thereof including, but not limited to, oils derived from plants and fruits such as citrus oils, fruit essences, peppermint oil, spearmint oil, other mint oils, clove oil, oil of wintergreen, anise and the like.
  • Artificial flavoring agents and components may also be used. Natural and artificial flavoring agents may be combined in any sensorially acceptable fashion.
  • the medicament or active is water soluble in the chewing gum, it preferably will include a base/emulsifier system which leads to the desired concentration of the medicament in the saliva (more hydrophilic balance). If the medicament or active is water insoluble, the chewing gum preferably includes a base/emulsifier system which leads to the desired concentration of the medicament in the saliva (more lipophilic balance).
  • the active agent or medicament is added, preferably, early on in the mix. The smaller the amount of active ingredient used, the more necessary it becomes to preblend that particular ingredient to assume uniform distribution throughout the batch of gum. Whether a preblend is used or not, the active agent or medicament should be added within the first five minutes of mixing. For faster release, the active agent may be added late in the process.
  • chewing gum is manufactured by sequentially adding the various chewing gum ingredients to a commercially available mixer known in the art. After the ingredients have been thoroughly mixed, the gum mass is discharged from the mixer and shaped into the desired form such as rolling sheets and cutting into sticks, extruding into chunks or casting into pellets, which are then coated or panned.
  • the ingredients are mixed by first melting the gum base and adding it to the running mixer.
  • the base may also be melted in the mixer itself.
  • Color or emulsifiers may also be added at this time.
  • a softener such as glycerin may also be added at this time, along with syrup and a portion of the bulking agent. Further parts of the bulking agent are added to the mixer. Flavoring agents are typically added with the final portion of the bulking agent.
  • Other optional ingredients are added to the batch in a typical fashion, well known to those of ordinary skill in the art.
  • Chewing gum base and chewing gum product have been manufactured conventionally using separate mixers, different mixing technologies and, often, at different factories.
  • One reason for this is that the optimum conditions for manufacturing gum base, and for manufacturing chewing gum from gum base and other ingredients such as sweeteners and flavors, are so different that it has been impractical to integrate both tasks.
  • Chewing gum base manufacture involves the dispersive
  • Chewing gum product manufacture involves combining the gum base with more delicate ingredients such as product softeners, bulk sweeteners, high intensity sweeteners and flavoring agents using distributive (generally lower shear) mixing, for shorter periods.
  • U.S. Patent 3,995,064, issued to Ehrgott et al. discloses the continuous manufacture of gum base using a sequence of mixers or a single variable mixer.
  • U.S. Patent 4,459,311 issued to DeTora et al., also discloses the continuous manufacture of gum base using a sequence of mixers.
  • Other continuous gum base manufacturing processes are disclosed in European Publication No. 0,273,809 (General Foods France) and in French Publication No. 2,635,441 (General Foods France).
  • U.S. Patent 5,045,325, issued to Lesko et al., and U.S. Patent 4,555,407, issued to Kramer et al. disclose processes for the continuous production of chewing gum products. In each case, however, the gum base is initially prepared separately and is simply added into the process.
  • U.S. Patent 5,045,325, issued to Lesko et al. and U.S. Patent 4,555,407, issued to Kramer et al.
  • 4,968,511 issued to D'Amelia et al., discloses a chewing gum product containing certain vinyl polymers which can be produced in a direct one-step process not requiring separate manufacture of gum base.
  • Active medicaments may also be added to chewing gum products made by a continuous process.
  • U.S. Patents 5,543,160 and 5,800,847 disclose a continuous process using a single extruder to make the gum base and the gum product.
  • U.S. Patents 5,397,580 and 5,523,097 disclose a continuous process using two or more extruders for base and chewing gum mixing.
  • U.S. Patents 5,419,919 and 5,571 ,543 disclose a continuous process using a paddle type mixer which has low pressure and high residence time for adequate mixing. Active medicaments, whether encapsulated, entrapped or not, can be added at any time during the continuous mixing process. Generally, actives would probably be added in the gum mixing sections.
  • Specific advantages to adding active medicaments to a continuous process of manufacturing gum are that more thorough mixing is accomplished in this type of process with lower amount of residence time of the active agent at high temperatures during processing.
  • the enclosed system used in continuous processing can result in more thorough mixing, better reproducibility of the amount of active within the gum matrix, and less loss in the amount of the active medicament.
  • Another method of treating the medicament or active agent is to physically isolate the active agent from other chewing gum ingredients to effect its release rate and stability.
  • the active agent may be added to the liquid inside a liquid center gum product.
  • the center fill of gum product may comprise one or more carbohydrate syrups, glycerin, thickeners, flavors, acidulants, colors, sugars and sugar alcohols in conventional amounts.
  • the ingredients are combined in a conventional manner.
  • the total amount of active agent may be dissolved in the center-fill liquid.
  • This method of using active agent in chewing gum may give a more controlled release rate, and may reduce or eliminate any possible reaction with gum base, flavor components, or other components, yielding improved shelf stability.
  • a liquid- center gum may also be coated with a sugar, polyol or film to yield a unique chewing gum product.
  • Another method of isolating medicaments or active agents from other chewing gum ingredients is to add active agents to the dusting compound of a chewing gum.
  • a rolling or dusting compound serves to reduce sticking to machinery as it is wrapped, and sticking to its wrapper after it is wrapped and being stored.
  • the rolling compound comprises active agents in combination with mannitol, sorbitol, sucrose, starch, calcium carbonate, talc, other orally acceptable substances or a combination thereof.
  • the rolling compound constitutes from about 0.25% to about 10.0% or about 1 % to about 3% of weight of the chewing gum composition.
  • This method of using active agents in the chewing gum can allow a lower usage level, can give a more controlled release rate, and can reduce or eliminate any possible reaction with the gum base, flavor components, or other components, yielding improved self stability.
  • Another method of isolating medicament or active agents is to use it in the coating/panning of a pellet chewing gum.
  • Pellet or ball gum is prepared as conventional chewing gum but formed into pellets that are pillow shaped, or into balls.
  • the pellets/balls can be then sugar coated or panned by conventional panning techniques to make a unique coated pellet gum.
  • the active agent may be soluble in flavor or can be blended with other powders often used in some types of conventional panning procedures.
  • Active agents are isolated from other gum ingredients which modifies its release rate from chewing gum. Levels of actives may be about 10 ppm to 5% by weight of chewing gum coating.
  • the weight of the coating may be about 20% to about 50% of the weight of the finished product, but may be as much as 75% of the total
  • panning modifiers including, but not limited to, gum arabic, maltodextrins, corn syrup, gelatin, cellulose type materials like carboxymethyl cellulose or hydroxymethyl cellulose, starch and modified starches, vegetables gums like alginates, locust bean gum, guar gum, and gum tragacanth, insoluble carbonates like calcium carbonate or magnesium carbonate and talc.
  • Antitack agents may also be added as panning modifiers, which allow the use of a variety of carbohydrates and sugar alcohols to be used in the development of new panned or coated gum products. Flavors may also be added with the sugar or sugarless coating and with the active to yield unique product characteristics.
  • pan coating could also isolate the active agent from the chewing gum ingredients.
  • This technique is referred to as a film coating and is more common for pharmaceuticals than in chewing gum, but procedures are similar.
  • a film like shellac, zein, or cellulose type material is applied onto a pellet-type product forming a thin film on the surface of the product.
  • the film is applied by mixing the polymer, plasticizer and a solvent (pigments are optional) and spraying the mixture onto the pellet surface. This is done in conventional type panning equipment, or in more advanced side-vended coating pans. Since most active agents may be alcohol soluble, they may be readily added with this type of film. When a solvent like an alcohol is used, extra precautions are needed to prevent fires and explosions, and specialized equipment must be used. Some film polymers can use water as the solvent in film coating.
  • a soft shell sugar or polyol coating may also be used over the film coated product.
  • the level of film coating applied to a pellet gum may be generally about 0.5% to about 3% of the gum product.
  • the level of overcoating of the hard or soft shell may be about 20% to about 60%.
  • the coating may contain ingredients such as flavoring agents, as well as artificial sweeteners and dispersing agents, coloring agents, film formers and binding agents.
  • Flavoring agents contemplated by the present invention include those commonly known in the art such as essential oils, synthetic flavors or mixtures thereof, including but not limited to oils derived from plants and fruits such as citrus oils, fruit essences, peppermint oil, spearmint oil, other mint oils, clove oil, oil of wintergreen, anise and the like.
  • the flavoring agents may be used in an amount such that the coating will contain from about 0.2% to about 3% flavoring agent, and preferably from about 0.7% to about 2.0% flavoring agent.
  • Artificial sweeteners contemplated for use in the coating include but are not limited to synthetic substances, saccharin, thaumatin, alitame, saccharin salts, aspartame, N-substituted APM derivatives such as neotame, sucralose and acesulfame-K.
  • the artificial sweetener may be added to the coating syrup in an amount such that the coating will contain from about 0.01 % to about 0.5%, and preferably from about 0.1 % to about 0.3% artificial sweetener.
  • Dispersing agents are often added to syrup coatings for the purpose of whitening and tack reduction.
  • Dispersing agents contemplated by the present invention to be employed in the coating syrup include titanium dioxide, talc, or any other antistick compound. Titanium dioxide is a presently preferred dispersing agent of the present invention.
  • the dispersing agent may be added to the coating syrup in amounts such that the coating will contain from about
  • Coloring agents are preferably added directly to the syrup in the dye or lake form.
  • Coloring agents contemplated by the present invention include food quality dyes.
  • Film formers preferably added to the syrup include methyl cellulose, gelatins, hydroxypropyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose and the like and combinations thereof.
  • Binding agents may be added either as an initial coating on the chewing gum center or may be added directly into the syrup.
  • Binding agents contemplated by the present invention include gum arabic, gum talha (another type of acacia), alginate, cellulosics, vegetable gums and the like.
  • the coating is initially present as a liquid syrup which contains from about 30% to about 80% or 85% of the coating ingredients previously described herein, and from about 15% or 20% to about 70% of a solvent such as water.
  • a solvent such as water.
  • the coating process is carried out in a rotating pan. Sugar or sugarless gum center tablets to be coated are placed into the rotating pan to form a moving mass.
  • the material or syrup which will eventually form the coating is applied or distributed over the gum center tablets. Flavoring agents may be added before, during and after applying the syrup to the gum centers. Once the coating has dried to form a hard surface, additional syrup additions can be made to produce a plurality of coatings or multiple layers of hard coating.
  • syrup is added to the gum center tablets at a temperature range of from about 100°F to about 240°F.
  • the syrup temperature is from about 130°F to about 200°F throughout the process in order to prevent the polyol or sugar in the syrup from crystallizing.
  • the syrup may be mixed with, sprayed upon, poured over, or added to the gum center tablets in any way known to those skilled in the art.
  • a plurality of layers is obtained by applying single coats, allowing the layers to dry, and then repeating the process.
  • the amount of solids added by each coating step depends chiefly on the concentration of the coating syrup. Any number of coats may be applied to the gum center tablet. Preferably, no more than about 75-100 coats are applied to the gum center tablets.
  • the present invention contemplates applying an amount of syrup sufficient to yield a coated comestible containing about 10% to about 65% coating. Where higher dosage of an active agent is needed, the final product may be higher than 65% coating.
  • a plurality of premeasured aliquots of coating syrup may be applied to the gum center tablets. It is contemplated, however, that the volume of aliquots of syrup applied to the gum center tablets may vary throughout the coating procedure.
  • the present invention contemplates drying the wet syrup in an inert medium.
  • a preferred drying medium comprises air.
  • forced drying air contacts the wet syrup coating in a temperature range of from about 70° to about 1 15°F. More preferably, the drying air is in the temperature range of from about 80° to about 100°F.
  • the invention also contemplates that the drying air possess a relative humidity of less than about 15 percent. Preferably, the relative humidity of the drying air is less than about 8 percent.
  • the drying air may be passed over and admixed with the syrup coated gum centers in any way commonly known in the art.
  • the drying air is blown over and around or through the bed of the syrup coated gum centers at a flow rate, for large scale operations, of about 2800 cubic feet per minute. If lower quantities of material are being processed, or if smaller equipment is used, lower flow rates would be used.
  • flavors have been added to a sugar coating of pellet gum to enhance the overall flavor of gum. These flavors include spearmint flavor, peppermint flavor, wintergreen flavor, and fruit flavors. These flavors are generally preblended with the coating syrup just prior to applying it to the core or added together to the core in one or more coating applications in a revolving pan containing the cores.
  • the coating syrup is very hot, about 130° to 200°F, and the flavor may volatilize if preblended with the coating syrup too early.
  • the concentrated coating syrup is applied to the gum cores as a hot liquid, the sugar or polyol allowed to crystallize, and the coating then dried with warm, dry air. This is repeated in about 30 to 80 applications to obtain a hard shell coated product having an increased weight gain of about 40% to 75%.
  • a flavor is applied with one, two, three or even four or more of these coating applications. Each time flavor is added, several non-flavored coatings are applied to cover the flavor before the next flavor coat is applied. This reduces volatilization of the flavor during the coating process.
  • an active agent is preblended with a gum arabic solution to become a paste and then applied to the cores.
  • the preblend may be mixed with a small amount of coating syrup before being applied. Forced air drying is then continued as the gum arabic binds the active agent to the cores. Then additional coatings are applied to cover the active agent and imbed the treated active agent in the coatings.
  • the gum formulas can be prepared as stick or tab products in the sugar or sugarless type formulations. These formulas can also be made in a pellet or pillow shape pellet or a round ball or any other shape of product for coating/panning. However, gum formulas for pellet centers are generally adjusted to a higher level of gum base to give a more consumer acceptable size of gum bolus. Keeping this in mind, if a coating of about 25% of the total product is added to a pellet core as sugar or polyols, the gum base in the pellet core should also be increased by 25%. Likewise, if a 33% coating is applied, the base levels should also be increased by 33%.
  • gum centers are usually formulated with about 25% to about 40% gum base with a corresponding decrease in the other ingredients except flavor. Even higher levels of base may be used if an active is added to a pellet coating.
  • flavors increase with the level of gum base as the base tends to bind flavors into the gum and more flavor is needed to give a good flavorful product.
  • flavors can also be added to the coating to give increased flavor impact and more flavor perception.
  • the formulas listed in Table 1 comprise various sugar-type formulas in which active medicament can be added to gum after it is dissolved in water or mixed with various aqueous solvents.
  • Dyclonine hydrochloride is an active medicament used as an oral anesthetic for sore throat. These formulas give a 3 gram stick with 3 mg of dyclonine hydrochloride.
  • Dyclonine hydrochloride powder can be added directly to the gum.
  • a 1 gram quantity of dyclonine hydrochloride can be dissolved in 9 grams of water giving a 10% solution and added to gum.
  • a 1 gram quantity of dyclonine hydrochloride can be dissolved in 9 grams of water and mixed with 10 grams of glycerin and added to the gum.
  • Example 4 A 1 gram quantity of dyclonine hydrochloride is mixed with 19 grams of glycerin giving a 5% solution and added to gum.
  • a 1 gram quantity of dyclonine hydrochloride is mixed with 19 grams of propylene glycol giving a 5% solution and added to gum.
  • a 1 gram quantity of dyclonine hydrochloride is dissolved in 9 grams of ethanol, which is then mixed with 90 grams of peppermint flavor and added to gum.
  • Example 7 A 1 gram quantity of dyclonine hydrochloride is dissolved in 168 grams of corn syrup and added to chewing gum.
  • dyclonine hydrochloride can be dissolved in water and emulsifiers can be added to the aqueous solution.
  • Example solutions can be prepared by dissolving 10 grams of dyclonine hydrochloride in 75 grams of water and adding 15 grams of emulsifiers of various hydrophilic-lipophilic balance (HLB) values to the solution. The mixtures can then be used in the following formulas.
  • Example 9 uses a mixture of dyclonine hydrochloride and water with no emulsifier.
  • the HLB value of the emulsifiers used in Examples 10-14 are listed in Table 2.
  • Tables 3 through 10 are examples of gum formulations that demonstrate formula variations in which dyclonine hydrochloride may be used.
  • the active agent may be added with or without encapsulation, or may be treated for fast release.
  • Examples 21 -24 in Table 3 demonstrates the use of dyclonine hydrochloride in low-moisture sugar formulations showing less than 2% theoretical moisture:
  • Examples 25-28 in Table 4 demonstrate the use of dyclonine hydrochloride in medium-moisture sugar formulations having about 2% to about 5% moisture.
  • Examples 29-32 in Table 5 demonstrate the use of dyclonine hydrochloride in high-moisture sugar formulations having more than about 5% moisture. TABLE 4 (WEIGHT PERCENT.
  • Examples 33-36 in Table 6 and Examples 37-44 in Tables 7 and 8 demonstrate the use of dyclonine hydrochloride in low- and high-moisture gums that are sugar-free. Low- moisture gums have less than about 2% moisture, and high-moisture gums have greater than 2% moisture. TABLE 6
  • Sorbitol liquid contains 70% sorbitol, 30% water
  • Table 9 shows sugar chewing formulations that can be made with various types of sugars. TABLE 9
  • Table 10 shows chewing gum formulations that are free of sugar. These formulations can use a wide variety of other non-sugar alditols.
  • EX. 63 EX. 64 EX. 65 EX. 66 EX. 67 EX. 68
  • High-intensity sweeteners such as aspartame, acesulfame K, or the salts of acesulfame, cyclamate and its salts, saccharin and its salts, alitame, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin, and combinations thereof may be used in any of the Examples listed in Tables 3, 4, 5, 6, 7, 8, 9 and 10. Since dyclonine hydrochloride may reduce sweetness, HIS may be used in sugar gum, and some of the alditols in sugar-free gum are less sweet than sugar so higher levels of HIS may be needed to obtain the proper level of sweetness.
  • HIS High-intensity sweeteners
  • High-intensity sweeteners may also be modified to control their release in those chewing gum formulations. This can be controlled by various methods of encapsulation, agglomeration, absorption, or a combination of methods to obtain either a fast or slow release of the sweetener. Sweetener combinations, some of which may be synergistic, may also be included in the gum formulations.
  • Example 69 - A 50% shellac, 50% active dyclonine hydrochloride powder mixture is obtained by spray drying an appropriate ratio alcohol/shellac/dyclonine hydrochloride mixture at 10% solids.
  • Example 70 A 70% Zein, 30% active dyclonine hydrochloride powder mixture is obtained by spray drying an alcohol/Zein/dyclonine hydrochloride mixture at 10% solids.
  • Example 71 A 40% shellac, 60% active dyclonine hydrochloride powder mixture is obtained by fluid-bed coating dyclonine hydrochloride with an alcohol/shellac solution at 20% solids.
  • Example 73 A 70% wax, 30% active dyclonine hydrochloride powder mixture is obtained by spray chilling a mixture of molten wax and dyclonine hydrochloride.
  • Example 74 A 70% Zein, 30% active dyclonine hydrochloride powder mixture is obtained by spray drying an aqueous mixture of dyclonine hydrochloride and Zein dispersed in an aqueous, high-pH (pH of 11.6-12.0) media at 10% solids. Examples 69-74 would all give nearly complete encapsulation and would delay the release of dyclonine hydrochloride when used in the sugarless gum formulation. The higher levels of coating would give a longer delayed release of sweetener than the lower levels of coating.
  • Example 75 A 30% hydroxpropylmethyl cellulose (HPMC), 70% dyclonine hydrochloride powder mixture is obtained by fluid-bed coating dyclonine hydrochloride with an aqueous solution of HPMC at 10% solids.
  • Example 76 A 50% maltodextrin, 50% active dyclonine hydrochloride powder mixture is obtained by spray drying an aqueous mixture of dyclonine hydrochloride and maltodextrin at 20% solids.
  • Example 77 A 40% gum arabic, 60% active dyclonine hydrochloride powder mixture is obtained by fluid-bed coating dyclonine hydrochloride with an aqueous solution of gum arabic at 20% solids.
  • coated dyclonine hydrochloride from Examples 75-77 when used in a chewing gum formula, would give a fast release of active agents.
  • Dyclonine hydrochloride could also be used in gum as an agglomerated active agent to give delayed sweetness release.
  • Agglomerated active agent can be prepared as in the following examples:
  • Example 78 A 15% hydroxypropylmethyl cellulose (HPMC), 85% active dyclonine hydrochloride powder mixture is prepared by agglomerating dyclonine hydrochloride and HPMC blended together, with water being added, and the resulting product being dried and ground.
  • HPMC hydroxypropylmethyl cellulose
  • Example 79 A 15% gelatin, 85% active dyclonine hydrochloride powder mixture is made by agglomerating dyclonine hydrochloride and gelatin blended together, with water being added, and the resulting product being dried and ground.
  • the gum formulas can be prepared as stick or tab products in the sugar or sugarless type formulations. These formulas can also be made in a pellet or pillow shape pellet or a round ball or any other shape of product for coating/panning. However, gum formulas are generally adjusted to a higher level of gum base to give a more consumer acceptable size of gum bolus.
  • the gum base in the pellet core should also be increased by 25%.
  • the base levels should also be increased by 33%.
  • gum centers are usually formulated with about 25% to about 40% gum base with a corresponding decrease in the other ingredients except flavor.
  • flavors increase with the level of gum base as the base tends to bind flavors into the gum and more flavor is needed to give a good flavorful product.
  • Gum center formulas may or may not contain dyclonine hydrochloride.
  • Formulations with or without active dyclonine hydrochloride can also be made similar to those found in Tables 3-8 for low, medium, and high moisture formulas. Higher levels of base may be used with a corresponding decrease in other ingredients. Also, other sugars and polyols may be used in the gum center as found in Tables 9-10.
  • Dyclonine hydrochloride may be added to a gum center only, or to a gum coating with none in the center, or to both center and coating. Coated gum pieces are about 1.5 grams, so to obtain 3 mg of dyclonine hydrochloride total piece must contain 0.2%.
  • Dyclonine hydrochloride can then be used in the coating formula on the various pellet gum formulations.
  • Table 12 shows some sugar and dextrose type formulas: TABLE 12 (DRY WEIGHT PERCENT)
  • gum arabic is blended in the sugar syrup.
  • gum arabic powder is dry charged after a gum arabic solution is applied in the first stages of coating, then this is followed by a hard shell coating of sugar solution or dextrose solution.
  • the above formulations are made by making a syrup by dissolving the sugar and gum arabic in solution at about 75% solids at boiling, and suspending titanium dioxide or calcium carbonate in this syrup. Some of the dextrose may be added as a dry charge which may also contain the active agent.
  • Dyclonine hydrochloride may be dissolved in water, not mixed with hot syrup, but added between coatings, or it may be added to the hot syrup and used in the early stages of coating or used throughout the coating process. Flavor is not mixed with the hot syrup, but added at low levels with one or more coats.
  • Dyclonine hydrochloride may be dissolved in flavor and added to the coating. After the final coats are applied and dried, wax is applied to give a smooth polish.
  • Dyclonine hydrochloride may also be used in coating of sugarless gum centers. Like sugar gum centers, the base formulation can be increased in proportion to the amount of coating applied to the center. Formulations with and without dyclonine hydrochloride similar to those found in Tables 6, 7 or 8 for low and high moisture gum can be used to make gum centers. Generally, the base level may be increased to 30-46% with the other ingredients proportionally reduced. Some typical gum formulas are in Table 13.
  • Lycasin and other polyols such as maltitol, xylitol, lactitol and hydrogenated isomaltulose may also be used in the gum center formulations at various levels similar to those shown in Table 10.
  • the texture may be adjusted by varying glycerin or sorbitol liquid.
  • Sweetness of the center formulation can also be adjusted by varying the level of high intensity sweetener.
  • Dyclonine hydrochloride may be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • xylitol sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • the above formulas are used to coat pellets by applying a xylitol/gum arabic solution in multiple coats and air drying. Color or whitener is also mixed in the solution.
  • Dyclonine hydrochloride may be dissolved in water and added between coating applications or mixed with the hot syrup and used in the early stages of coating or used throughout the coating process. After pellets have been coated and dried, talc and wax are added to give a polish. For examples 115-120, erythritol may be substituted for xylitol in Table 14. In some cases more gum arabic may be needed to give good binding.
  • gum arabic For coating formulas based on sorbitol, maltitol, lactitol, and hydrogenated isomaltulose, gum arabic can be used as a binder and film former, and a crystallization modifier to help facilitate coating. Generally these polyols are more difficult to coat using only a straight syrup, but with proper technique a good smooth hard shell can be made. However, it may be preferable to add a dry charge to quicken the drying process before the pellets get too sticky. The following formulations may be used.
  • Maltitol powder is used to dry charge in the early stages of coating. Maltitol, gum arabic, and whitener are blended into a syrup and applied to pellets. Dyclonine hydrochloride may be applied in a similar manner as in the previous xylitol coating or may be preblended with the dry charge material.
  • coatings with sorbitol, lactitol, and hydrogenated isomaltulose may be made in the coating formulas in Table 15 by replacing maltitol with any one of the other polyols and maltitol powder with the polyol powder.
  • the other polyols may become sticky during the coating and drying process, so the dry powder charge may be needed to give the proper drying.
  • less gum arabic could be used and a more pure polyol syrup could be used to give a smooth surface.
  • the dry charge would only be used in the early stages of the coating process.
  • ingredients may be added to the dry charge to help absorb moisture.
  • These materials could be inert such as talc, calcium carbonate, magnesium carbonate, starches, gums like dyclonine hydrochloride, gum talha, gum arabic or other moisture absorbing materials.
  • powdered sweeteners or flavors could be added with the dry charge, along with the active medicament.
  • Some polyols such as sorbitol, maltitol, lactitol, erythritol, or hydrogenated isomaltulose are not sufficiently sweet compared to sugar or xylitol, so high intensity sweeteners may be added to the coating, such as aspartame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, alitame, sucralose, thaumatin, monellin, dihydrochalcone, glycyrrhizin, neotame, and combinations thereof. If a hot syrup is applied, heat may degrade the sweetener so only stable sweeteners should be used. Generally high intensity sweeteners are added with the polyol/gum arabic solution to obtain an even distribution in the coatings.
  • the formulas listed in Table 16 comprise various sugar-type formulas in which chlorpheniramine maleate can be added to gum after it is dissolved in water or mixed with various aqueous solvents. Chlorpheniramine maleate is an active medicament used as an antihistamine. These formulas give a 3 gram stick with 4 mg of chlorpheniramine maleate. TABLE 16 (WEIGHT PERCENT)
  • Chlorpheniramine maleate powder can be added directly to the gum.
  • a 1 gram quantity of chlorpheniramine maleate can be dissolved in 9 grams of water giving a 10% solution and added to gum.
  • a 1 gram quantity of chlorpheniramine maleate can be dissolved in 9 grams of water and mixed with 10 grams of glycerin and added to the gum.
  • Example 130 A 1 gram quantity of chlorpheniramine maleate is mixed with 19 grams of glycerin giving a 5% solution and added to gum.
  • Example 132 A 1 gram quantity of chlorpheniramine maleate is mixed with 9 grams of peppermint flavor giving a 10% solution and added to gum.
  • Example 132 A 1 gram quantity of chlorpheniramine maleate is mixed with 9 grams of peppermint flavor giving a 10% solution and added to gum.
  • Example 135 uses a mixture of chlorpheniramine maleate and water with no emulsifier.
  • HLB value of the emulsifiers used in Examples 136-140 are listed in Table 17.
  • EX. 135 EX. 136 EX. 137 EX. 138 EX. 139 EX. 140
  • Examples 147-150 in Table 18 demonstrate the use of chlorpheniramine maleate in low-moisture sugar formulations showing less than 2% theoretical moisture: TABLE 18 (WEIGHT PERCENT)
  • Examples 151-154 in Table 19 demonstrate the use of chlorpheniramine maleate in medium-moisture sugar formulations having about 2% to about 5% moisture.
  • Examples 155-158 in Table 20 demonstrate the use of chlorpheniramine maleate in high-moisture sugar formulations having more than about 5% moisture.
  • Examples 159-162 in Table 21 and Examples 163-170 in Tables 22 and 23 demonstrate the use of chlorpheniramine maleate in low- and high- moisture gums that are sugar-free. Low- moisture gums have less than about 2% moisture, and high-moisture gums have greater than 2% moisture. TABLE 21
  • Sorbitol liquid contains 70% sorbitol, 30% water
  • Hydrogenated starch hydrolyzate syrup ** Glycerin and HSH syrup may be blended or co-evaporated
  • Table 24 shows sugar chewing formulations that can be made with various types of sugars.
  • EX. 171 EX. 172 EX. 173 EX. 174 EX. 175 EX. 176
  • Table 25 shows chewing gum formulations that are free of sugar. These formulations can use a wide variety of other non-sugar alditols.
  • High-intensity sweeteners such as aspartame, acesulfame K, or the salts of acesulfame, cyclamate and its salts, saccharin and its salts, alitame, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin, and combinations thereof may be used in any of the Examples listed in Tables 18-25. Since chlorpheniramine maleate may reduce sweetness, HIS may be used in sugar gum, and some of the alditols in sugar-free gum are less sweet than sugar so higher levels of HIS may be needed to obtain the proper level of sweetness.
  • HIS High-intensity sweeteners
  • High-intensity sweeteners may also be modified to control their release in those chewing gum formulations. This can be controlled by various methods of encapsulation, agglomeration, absorption, or a combination of methods to obtain either a fast or slow release of the sweetener. Sweetener combinations, some of which may be synergistic, may also be included in the gum formulations.
  • the gum formulas can be prepared as stick or tab products in the sugar or sugarless type formulations. These formulas can also be made in a pellet or pillow shape pellet or a round ball or any other shape of product for coating/panning. However, gum formulas are generally adjusted to a higher level of gum base to give a more consumer acceptable size of gum bolus.
  • gum centers are usually formulated with about 25% to about 40% gum base with a corresponding decrease in the other ingredients except flavor.
  • flavors increase with the level of gum base as the base tends to bind flavors into the gum and more flavor is needed to give a good flavorful product.
  • flavors can also be added to the coating to give increased flavor impact and more flavor perception.
  • Gum center formulas may or may not contain chlorpheniramine maleate.
  • Formulations with or without active chlorpheniramine maleate can also be made similar to those found in Tables 18-23 for low, medium, and high moisture formulas. Higher levels of base may be used with a corresponding decrease in other ingredients. Also, other sugars are polyols may be used in the gum center as found in Tables 24 and 25. Chlorpheniramine maleate may be added to a gum center only, or to a gum coating with none in the center, or to both center and coating. Coated gum pieces are about 1.5 grams, so to obtain 4 mg of chlorpheniramine maleate total piece must contain 0.27%.
  • Chlorpheniramine maleate can be used in the coating formula on the various pellet gum formulations.
  • Table 27 shows some sugar and dextrose type formulas:
  • EX. 201 EX. 202 EX. 203 EX . 204 EX. 205 EX. 206
  • the above formulations are made by making a syrup by dissolving the sugar and gum arabic in solution at about 75% solids at boiling, and suspending titanium dioxide or calcium carbonate in this syrup. Some of the dextrose may be added as a dry charge, which may also contain the active. Chlorpheniramine maleate may be dissolved in water, not mixed with hot syrup, but applied between coatings, or it may be added to the hot syrup and used in the early stages of coating or used throughout the coating process. Flavor is not mixed with the hot syrup, but added at low levels with one or more coats. Chlorpheniramine maleate may be dissolved in flavor and added to the coating. After the final coats are applied and dried, wax is applied to give a sr ⁇ ooth polish.
  • Chlorpheniramine maleate may also be used in coating of sugarless gum centers. Like sugar gum centers, the base formulation can be increased in proportion to the amount of coating applied to the center. Formulations with and without chlorpheniramine maleate similar to those found in Tables 21-25 for low and high moisture gum can be used to make gum centers. Generally, the base level may be increased to 30-46% with the other ingredients proportionally reduced. Some typical gum formulas are in Table 28.
  • CHLORPHENIRAMINE MALEATE 0 ' a) Lycasin brand hydrogenated starch hydrolyzate used instead of sorbitol liquid b) This material may be dissolved in water, glycerin, sorbitol liquid, or HSH. c) All of the active agent is in the coating, which comprises 33% of the product. d) This example required 50% of the product to be a coating with no active agent in the coating, to give a gum product with 0.27% active agent. In the above center formulations, the high intensity sweetener used is aspartame.
  • Lycasin and other polyols such as maltitol, xylitol, lactitol and hydrogenated isomaltulose may also be used in the gum center formulations at various levels similar to those shown in Table 25.
  • the texture may be adjusted by varying glycerin or sorbitol liquid.
  • Sweetness of the center formulation can also be adjusted by varying the level of high intensity sweetener.
  • Chlorpheniramine maleate may be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • xylitol sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • the above formulas are used to coat pellets by applying a xylitol/gum arabic solution in multiple coats and air drying. Color or whitener is also mixed in the solution. Chlorpheniramine maleate may be dissolved in water or flavor and added between coating applications or mixed with the hot syrup and used in the early stages of coating or used throughout the coating process. After pellets have been coated and dried, talc and wax are added to give a polish.
  • gum arabic can be used as a binder and film former, and a crystallization modifier to help facilitate coating.
  • these polyols are more difficult to coat using only a straight syrup, but with proper technique a good smooth hard shell can be made.
  • the following formulations may be used. TABLE 30 (DRY WEIGHT PERCENT)
  • Maltitol powder is used to dry charge in the early stages of coating. Maltitol, gum arabic, and whitener are blended into a syrup and applied to pellets. After all coating is applied and dried, talc and wax are added to give a polish. Chlorpheniramine maleate may be applied in a similar manner as in the previous xylitol coating, or may be preblended with the dry charge material.
  • coatings with sorbitol, lactitol, and hydrogenated isomaltulose may be made in the coating formulas in Table 30 by replacing maltitol with any one of the other polyols and maltitol powder with the polyol powder.
  • the other polyols may become sticky during the coating and drying process, so the dry powder charge may be needed to give the proper drying.
  • less gum arabic could be used and a more pure polyol syrup could be used to give a smooth surface.
  • the dry charge would only be used in the early stages of the coating process.
  • ingredients may be added to the dry charge to help absorb moisture.
  • These materials could be inert such as talc, calcium carbonate, magnesium carbonate, starches, gums like dyclonine hydrochloride, gum talha, gum arabic or other moisture absorbing materials.
  • powdered sweeteners or flavors could be added with the dry charge.
  • Some polyols such as sorbitol, maltitol, lactitol, erythritol, or hydrogenated isomaltulose are not sufficiently sweet compared to sugar or xylitol, so high intensity sweeteners may be added to the coating, such as aspartame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, alitame, sucralose, thaumatin, monellin, dihydrochalcone, glycyrrhizin, neotame, and combinations thereof. If a hot syrup is applied, heat may degrade the sweetener so only stable sweeteners should be used. Generally high intensity sweeteners are added with the polyol/gum arabic solution to obtain an even distribution in the coatings.
  • the formulas listed in Table 31 comprise various sugar-type formulas in which active medicament can be added to gum after it is dissolved in water or mixed with various aqueous solvents.
  • Pseudoephedrine hydrochloride (SudafedTM) is an active medicament used as a nasal decongestant. These formulas give a 3 gram stick with 30 mg of pseudoephedrine hydrochloride.
  • Pseudoephedrine hydrochloride powder can be added directly to the gum.
  • Example 231 A 20 gram quantity of pseudoephedrine hydrochloride can be dissolved in 80 grams of water giving a 20% solution and added to gum.
  • a 10 gram quantity of pseudoephedrine hydrochloride can be dissolved in 50 grams of water and mixed with 50 grams of glycerin and added to the gum.
  • a 10 gram quantity of pseudoephedrine hydrochloride is mixed with 90 grams of glycerin giving a 10% solution and added to gum.
  • Example 234 A 10 gram quantity of pseudoephedrine hydrochloride is mixed with 90 grams of propylene glycol giving a 10% solution and added to gum.
  • a 10 gram quantity of pseudoephedrine hydrochloride is dissolved in 10 grams of peppermint flavor and added to gum.
  • a 10 gram quantity of pseudoephedrine hydrochloride is dissolved in 168 grams of corn syrup and added to chewing gum.
  • pseudoephedrine hydrochloride can be dissolved in water and emulsifiers can be added to the aqueous solution.
  • Example solutions can be prepared by dissolving 20 grams of pseudoephedrine hydrochloride in 65 grams of water and adding 15 grams of emulsifiers of various hydrophilic-lipophilic balance (HLB) values to the solution. The mixtures can then be used in the following formulas.
  • Example 238 uses a mixture of pseudoephedrine hydrochloride and water with no emulsifier. The HLB value of the emulsifiers used in Examples 238-243 are listed in Table 32.
  • the formulations made in Examples 238-243 can be changed in that the flavor can be mixed together with the aqueous active agent solution and emulsified before adding the mixture to the gum batch.
  • Tables 33 through 40 are examples of gum formulations that demonstrate formula variations in which pseudoephedrine hydrochloride may be used.
  • the active agent may be added with or without encapsulation or may be treated for fast release.
  • Examples 244-247 in Table 33 demonstrate the use of pseudoephedrine hydrochloride in low-moisture sugar formulations showing less than 2% theoretical moisture:
  • Corn syrup is evaporated to 85% solids, 15% moisture b> Glycerin and syrup may be blended and co-evaporated
  • Examples 248-251 in Table 34 demonstrate the use of pseudoephedrine hydrochloride in medium-moisture sugar formulations having about 2% to about 5% moisture.
  • Examples 252-255 in Table 35 demonstrate the use of pseudoephedrine hydrochloride in high-moisture sugar formulations having more than about 5% moisture.
  • CORN SYRUP a 15.0 15.0 13.0 12.5
  • Examples 256-259 in Table 36 and Examples 260-267 in Tables 37 and 38 demonstrate the use of pseudoephedrine hydrochloride in low- and high-moisture gums that are sugar-free. Low- moisture gums have less than about 2% moisture, and high-moisture gums have greater than 2% moisture. TABLE 36 (WEIGHT PERCENT)
  • Sorbitol liquid contains 70% sorbitol, 30% water
  • Hydrogenated starch hydrolyzate syrup ** Glycerin and HSH syrup may be blended or co-evaporated
  • Table 39 shows sugar chewing formulations that can be made with various types of sugars.
  • Table 40 shows chewing gum formulations that are free of sugar. These formulations can use a wide variety of other non-sugar alditols.
  • High-intensity sweeteners such as aspartame, acesulfame K, or the salts of acesulfame, cyclamate and its salts, saccharin and its salts, alitame, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin, and combinations thereof may be used in any of the Examples listed in Tables 33-40. Since pseudoephedrine hydrochloride may reduce sweetness, HIS may be used in sugar gum, and some of the alditols in sugar-free gum are less sweet than sugar so higher levels of HIS may be needed to obtain the proper level of sweetness.
  • HIS High-intensity sweeteners
  • High-intensity sweeteners may also be modified to control their release in those chewing gum formulations. This can be controlled by various methods of encapsulation, agglomeration, absorption, or a combination of methods to obtain either a fast or slow release of the sweetener. Sweetener combinations, some of which may be synergistic, may also be included in the gum formulations.
  • the gum formulas can be prepared as stick or tab products in the sugar or sugarless type formulations. These formulas can also be made in a pellet or pillow shape pellet or a round ball or any other shape of product for coating/panning.
  • gum formulas are generally adjusted to a higher level of gum base to give a more consumer acceptable size of gum bolus.
  • gum centers are usually formulated with about 25% to about 40% gum base with a corresponding decrease in the other ingredients except flavor.
  • flavors increase with the level of gum base as the base tends to bind flavors into the gum and more flavor is needed to give a good flavorful product.
  • flavors can also be added to the coating to give increased flavor impact and more flavor perception.
  • Formulations with or without active pseudoephedrine hydrochloride can also be made similar to those found in Tables 33-38 for low, medium, and high moisture formulas. Higher levels of base may be used with a corresponding decrease in other ingredients. Also, other sugars are polyols may be used in the gum center as found in Tables 39 and 40. Pseudoephedrine hydrochloride may be added to a gum center only, or to a gum coating with none in the center, or to both center and coating. Coated gum pieces are about 1.5 grams per piece, so to obtain 30 mg of pseudoephedrine hydrochloride in two gum pieces, total piece must contain 1.0%.
  • Pseudoephedrine hydrochloride can be used in the coating formula on the various pellet gum formulations.
  • Table 42 shows some sugar and dextrose type formulas:
  • All of the active agent is in the coating, which comprises 33% of the product.
  • the above formulations are made by making a syrup by dissolving the sugar and gum arabic in solution at about 75% solids at boiling, and suspending titanium dioxide or calcium carbonate in this syrup.
  • Pseudoephedrine hydrochloride may be dissolved in water, not mixed with hot syrup, but applied between coatings, or it may be added to the hot syrup and used in the early stages of coating or used throughout the coating process. Flavor is not mixed with the hot syrup, but added at low levels with one or more coats.
  • Pseudoephedrine hydrochloride may be dissolved in flavor and added to the coating. After the final coats are applied and dried, wax is applied to give a smooth polish.
  • some of the sugar or dextrose may be added as a dry charge, which may also contain the active.
  • Powder and/or crystalline sugar may be used.
  • gum arabic powder is blended in the sugar syrup.
  • gum arabic powder is dry charged after a gum arabic solution is applied in the first stages of coating, then this is followed by a hard shell coating of sugar solution or dextrose solution.
  • Pseudoephedrine hydrochloride may also be used in coating of sugarless gum centers. Like sugar gum centers, the base formulation can be increased in proportion to the amount of coating applied to the center.
  • Formulations with and without pseudoephedrine hydrochloride similar to those found in Tables 33-38 for low and high moisture gum can be used to make gum centers.
  • the base level may be increased to 30-46% with the other ingredients proportionally reduced.
  • Some typical gum formulas are in Table 44.
  • EX. 314 EX. 315 EX. 316 EX. 317 EX. 318 EX. 319 EX. 320
  • Lycasin brand hydrogenated starch hydrolyzate used instead of sorbitol liquid
  • This material may be dissolved in water, glycerin, sorbitol liquid, or HSH.
  • All of the active agent is in the coating, which comprises 33% of the product.
  • This example required 50% of the product to be a coating with no active agent in the coating, to give a gum product with 1 % active agent.

Abstract

L'invention se rapporte à un procédé de fabrication d'un chewing-gum contenant un agent actif à libération prolongée, ainsi qu'au chewing-gum ainsi fabriqué. Ledit procédé consiste à modifier physiquement les caractéristiques de libération de l'agent actif par enrobage et séchage. L'agent actif est enrobé par encapsulation, partiellement enrobé par agglomération, piégé par absorption ou soumis à de multiples étapes de traitement par encapsulation, agglomération et absorption. L'agent actif enrobé est ensuite de préférence soumis à un co-séchage et à une réduction à l'état de particules aux fins d'obtention d'un agent actif à libération modifiée, destiné à être utilisé dans un chewing-gum. L'agent actif peut également être introduit dans l'enrobage d'un produit à mâcher, en tant que produit de finition appliqué sur le produit de type chewing-gum, ou en tant que liquide constituant le centre du produit de type chewing-gum.
PCT/US1999/029792 1996-11-27 1999-12-14 Chewing-gum contenant des agents medicamenteux actifs WO2000035298A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
BR9916304-7A BR9916304A (pt) 1998-12-15 1999-12-14 Goma de mascar contendo agentes ativos demedicamentos
EP99966283A EP1221863A4 (fr) 1998-12-15 1999-12-14 Chewing gum contenant des agents actifs medicamenteux
US09/621,780 US6949264B1 (en) 1996-11-27 2000-07-21 Nutraceuticals or nutritional supplements and method of making
US09/714,571 US6531114B1 (en) 1999-04-06 2000-11-16 Sildenafil citrate chewing gum formulations and methods of using the same
US09/748,699 US6541048B2 (en) 1999-09-02 2000-12-22 Coated chewing gum products containing an acid blocker and process of preparing
US10/280,688 US20030180414A1 (en) 1996-11-27 2002-10-25 Method of controlling release of bitterness inhibitors in chewing gum and gum produced thereby

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
PCT/US1996/018977 WO1998023165A1 (fr) 1996-11-27 1996-11-27 Procede permettant de reguler la liberation de cafeine dans de la gomme a macher et gomme ainsi produite
US09/308,972 US6165516A (en) 1996-11-27 1996-11-27 Method of controlling release of caffeine in chewing gum
US60/112,389 1998-12-15
US09/286,818 1999-04-06
US38921199A 1999-09-02 1999-09-02
US09/389,211 1999-09-02

Related Parent Applications (5)

Application Number Title Priority Date Filing Date
PCT/US1996/018977 Continuation-In-Part WO1998023165A1 (fr) 1996-11-27 1996-11-27 Procede permettant de reguler la liberation de cafeine dans de la gomme a macher et gomme ainsi produite
US09/308,972 Continuation-In-Part US6165516A (en) 1996-11-27 1996-11-27 Method of controlling release of caffeine in chewing gum
US28681899A Continuation-In-Part 1996-11-27 1999-04-06
US38921199A Continuation-In-Part 1996-11-27 1999-09-02
US38921199A Continuation 1996-11-27 1999-09-02

Related Child Applications (3)

Application Number Title Priority Date Filing Date
PCT/US1999/029742 Continuation-In-Part WO2000035296A1 (fr) 1996-11-27 1999-12-14 Liberation amelioree d'agents medicamenteux actifs par un enrobage de chewing-gum
US09/621,780 Continuation US6949264B1 (en) 1996-11-27 2000-07-21 Nutraceuticals or nutritional supplements and method of making
US09/621,643 Continuation US6627234B1 (en) 1998-12-15 2000-07-21 Method of producing active agent coated chewing gum products

Publications (1)

Publication Number Publication Date
WO2000035298A1 true WO2000035298A1 (fr) 2000-06-22

Family

ID=27378137

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US1999/029792 WO2000035298A1 (fr) 1996-11-27 1999-12-14 Chewing-gum contenant des agents medicamenteux actifs
PCT/US1999/029742 WO2000035296A1 (fr) 1996-11-27 1999-12-14 Liberation amelioree d'agents medicamenteux actifs par un enrobage de chewing-gum

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US1999/029742 WO2000035296A1 (fr) 1996-11-27 1999-12-14 Liberation amelioree d'agents medicamenteux actifs par un enrobage de chewing-gum

Country Status (1)

Country Link
WO (2) WO2000035298A1 (fr)

Cited By (221)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6471945B2 (en) 2000-03-10 2002-10-29 Warner-Lambert Company Stain removing chewing gum and confectionery compositions, and methods of making and using the same
US6485739B2 (en) 2000-03-10 2002-11-26 Warner-Lambert Company Stain removing chewing gum and confectionery compositions, and methods of making and using the same
EP1467715A1 (fr) 2002-01-15 2004-10-20 UCB Farchim S.A. Formulations pour l'adminstration orale de composes actifs
US7078052B2 (en) 1999-04-06 2006-07-18 Wm. Wrigley Jr. Company Pharmaceutical chewing gum formulations
WO2006090388A2 (fr) 2005-02-25 2006-08-31 The State Of Israel, Ministry Of Agriculture & Rural Development, Agricultural Research Organization, (A.R.O.), Volcani Center Composition pour administration par les muqueuses de cultures de cellules de fruit et de preparations tirees de ces cultures, et methodes de fabrication
WO2006097817A1 (fr) 2005-03-17 2006-09-21 Pfizer Japan Inc. Derives de n-(n-sulfonylaminomethyl)cyclopropanecarboxamide utilises pour traiter une douleur
WO2006124366A2 (fr) 2005-05-18 2006-11-23 Mcneil-Ppc, Inc. Aromatisant pour chewing gums contenant un medicament
WO2007072163A2 (fr) 2005-12-20 2007-06-28 Pfizer Limited Derives de pyrimidine
US7241810B2 (en) 2004-03-23 2007-07-10 Pfizer Inc Formamide derivatives for the treatment of diseases
US7268147B2 (en) 2003-05-15 2007-09-11 Pfizer Inc Compounds useful for the treatment of diseases
US7309790B2 (en) 2003-10-03 2007-12-18 Pfizer Inc Chemical compounds
US20080014302A1 (en) * 2004-08-25 2008-01-17 Cadbury Adams Usa Llc Multi-region chewing gum composition including isomalt gum region
WO2008050199A2 (fr) 2006-10-23 2008-05-02 Pfizer Japan Inc. Composés de phénylméthyl bicyclocarboxyamide substitués
WO2008104547A1 (fr) * 2007-02-26 2008-09-04 Revolymer Limited Gomme à mâcher médicamentée
US7456164B2 (en) 2004-05-07 2008-11-25 Pfizer, Inc 3- or 4-monosubtituted phenol and thiophenol derivatives useful as H3 ligands
EP2017259A2 (fr) 2005-12-21 2009-01-21 Pfizer Products Inc. Preparation d'acides gamma-amines ayant une affinité pour la protéine alpha-2-delta
US7511057B2 (en) 2004-08-12 2009-03-31 Pfizer Inc. Triazolopyridinylsulfanyl derivatives as p38 MAP kinase inhibitors
US7538141B2 (en) 2004-03-23 2009-05-26 Alan Daniel Brown Compounds for the treatment of diseases
US7538134B2 (en) 2005-06-15 2009-05-26 Pfizer Inc. Substituted arylpyrazoles
US7557121B2 (en) 2004-05-12 2009-07-07 Pfizer Inc Tetrahydronaphthyridine derivatives
EP2083633A1 (fr) * 2006-10-11 2009-08-05 WM. Wrigley Jr., Company Véhicules d'administration orale contenant un médicament traditionnel chinois ou un extrait de celui-ci
US7595329B2 (en) 2004-06-15 2009-09-29 Pfizer Inc Benzimidazolone carboxylic acid derivatives
US7598393B2 (en) 2004-11-02 2009-10-06 Pfizer Inc. Sulfonyl benzimidazole derivatives
US7618972B2 (en) 2005-03-21 2009-11-17 Pfizer Inc Substituted triazole derivatives as oxytocin antagonists
US7629358B2 (en) 2004-03-17 2009-12-08 Pfizer Inc Compounds useful for the treatment of diseases
US7642350B2 (en) 2005-05-04 2010-01-05 Pfizer Limited Purine derivatives
US7645786B2 (en) 2005-06-15 2010-01-12 Pfizer Inc. Substituted arylpyrazoles
US7649002B2 (en) 2004-02-04 2010-01-19 Pfizer Inc (3,5-dimethylpiperidin-1yl)(4-phenylpyrrolidin-3-yl)methanone derivatives as MCR4 agonists
EP2163253A1 (fr) 2008-09-15 2010-03-17 Charité-Universitätsmedizin Berlin Extraits de la plante Hornstedtia scyphifera et ses effets immunosuppresseurs
WO2010058858A1 (fr) 2008-11-21 2010-05-27 ラクオリア創薬株式会社 Nouveau dérivé de pyrazole-3-carboxamide doté d’une activité antagoniste du récepteur 5-ht2b
US7727565B2 (en) 2004-08-25 2010-06-01 Cadbury Adams Usa Llc Liquid-filled chewing gum composition
US20100136164A1 (en) * 2004-08-25 2010-06-03 Cadbury Adams Usa Llc Package assembly for multi-modality taste chewing gum compositions
US7737163B2 (en) 2004-06-15 2010-06-15 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
EP2196201A2 (fr) 2002-12-13 2010-06-16 Warner-Lambert Company LLC Combinaison d'un ligand alpha-2-delta avec un inhibiteur de pdev ou avec un antagoniste muscarinique pour traiter les symptomes des voies urinaires inferieures
WO2010079443A1 (fr) 2009-01-12 2010-07-15 Pfizer Limited Dérivés sulfonamides
US7776885B2 (en) 2003-09-03 2010-08-17 Pfizer, Inc. Benzimidazolone compounds having 5-HT4 receptor agonistic activity
WO2010103070A2 (fr) 2009-03-12 2010-09-16 Charité - Universitätsmedizin Berlin Variants de la protéine morphogénétique osseuse 2 (bmp2) avec une sensibilité réduite aux antagonistes des bmp
EP2233502A1 (fr) 2009-03-27 2010-09-29 Deutsches Rheuma-Forschungszentrum Berlin Anticorps spécifiques à l'antigène syalilé pour le traitement ou prophylaxie des réactions immunitaires inflammatoires non désirables et leurs procédés de production
EP2236516A1 (fr) 2009-03-31 2010-10-06 Charité-Universitätsmedizin Berlin (Charité) Polypeptides et utilisation associée pour le traitement d'une lésion neuronale traumatique ou dégénérative
EP2246045A1 (fr) 2007-08-13 2010-11-03 McNeil-PPC, Inc. Procédé de stabilisation de phényléphrine
WO2010136940A1 (fr) 2009-05-29 2010-12-02 Pfizer Limited Nouveaux agonistes du récepteur des glucocorticoïdes
EP2258700A1 (fr) 2006-05-09 2010-12-08 Pfizer Products Inc. Dérivés d'acides aminés cycloalkyles et compositions pharmaceutiques les contenant
US7858643B2 (en) 2004-08-26 2010-12-28 Agouron Pharmaceuticals, Inc. Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
EP2266563A1 (fr) 2009-06-11 2010-12-29 Charité-Universitätsmedizin Berlin (Charité) Utilisation d'antagonistes de récepteur opioïde pour le traitement aigu des états d'éveil paraphiliques
WO2011004276A1 (fr) 2009-07-06 2011-01-13 Pfizer Limited Inhibiteurs du virus de l’hépatite c
WO2011077313A1 (fr) 2009-12-22 2011-06-30 Pfizer Inc. Pipéridinecarboxamides en tant qu'inhibiteurs de mpges - 1
WO2011121558A1 (fr) 2010-04-02 2011-10-06 Phivco-1 Llc Traitement d'association comprenant un antagoniste du récepteur ccr5, un inhibiteur de la protéase du vih-1 et un accélérateur pharmacocinétique
WO2011138751A2 (fr) 2010-05-04 2011-11-10 Pfizer Inc. Dérivés hétérocycliques destinés au traitement de maladies
WO2011152721A1 (fr) 2010-05-31 2011-12-08 Umc St. Radboud Dérivés de l'acide pantothénique et leur utilisation pour le traitement du paludisme
WO2011154871A1 (fr) 2010-06-10 2011-12-15 Pfizer Limited Inhibiteurs du virus de l'hépatite c
WO2012004714A2 (fr) 2010-07-09 2012-01-12 Pfizer Limited Composés chimiques
WO2012004706A2 (fr) 2010-07-09 2012-01-12 Pfizer Limited Composés chimiques
WO2012004743A1 (fr) 2010-07-09 2012-01-12 Pfizer Limited Benzènesulfonamides utiles en tant qu'inhibiteurs des canaux sodiques
WO2012007877A2 (fr) 2010-07-12 2012-01-19 Pfizer Limited Composés chimiques
WO2012007868A2 (fr) 2010-07-12 2012-01-19 Pfizer Limited Composés chimiques
WO2012007869A2 (fr) 2010-07-12 2012-01-19 Pfizer Limited Composés chimiques
WO2012007861A1 (fr) 2010-07-12 2012-01-19 Pfizer Limited Dérivés de n-sulfonylbenzamide utiles comme inhibiteurs du canal sodique voltage-dépendant
WO2012007883A1 (fr) 2010-07-12 2012-01-19 Pfizer Limited Composés chimiques
US8133476B2 (en) 2006-04-05 2012-03-13 Cadbury Adams Usa Llc Calcium phosphate complex and salts in oral delivery systems
US8138188B2 (en) 2006-02-23 2012-03-20 Pfizer Inc. Melanocortin type 4 receptor agonist piperidinoylpyrrolidines
WO2012042421A1 (fr) 2010-09-29 2012-04-05 Pfizer Inc. Procédé de traitement de la croissance cellulaire anormale
EP2441840A1 (fr) 2005-07-18 2012-04-18 Protalix Ltd. Administration mucosale ou enterale de macromolecules biologiquement actives
WO2012066442A1 (fr) 2010-11-15 2012-05-24 Pfizer Limited Inhibiteurs de la réplication du vih
EP2457900A1 (fr) 2010-11-25 2012-05-30 Almirall, S.A. Nouveaux dérivés de pyrazole présentant un comportement antagoniste CRTH2
WO2012069202A1 (fr) 2010-11-26 2012-05-31 Almirall,S.A. Dérivés d'imidazo[1,2-b]pyridazine et d'imidazo[4,5-b]pyridine en tant qu'inhibiteurs des jak
US8211980B2 (en) 2004-08-12 2012-07-03 Revolymer Limited Polymeric materials having reduced tack, methods of making the materials and chewing gum compositions containing such materials
WO2012095781A1 (fr) 2011-01-13 2012-07-19 Pfizer Limited Dérivés d'indazole comme inhibiteurs des canaux sodiques
EP2489663A1 (fr) 2011-02-16 2012-08-22 Almirall, S.A. Composés en tant qu'inhibiteurs de la syk kinase
US8252269B2 (en) 2006-04-05 2012-08-28 Cadbury Adams Usa, Llc Impact of calcium phosphate complex on dental caries
WO2012120398A1 (fr) 2011-03-04 2012-09-13 Pfizer Limited Dérivés de carboxamide substitués par aryle en tant que modulateurs de trpm8
US8278355B2 (en) 2006-09-12 2012-10-02 Therexcell Pharma Inc. Isovaline for treatment of pain
WO2012137089A1 (fr) 2011-04-05 2012-10-11 Pfizer Limited Dérivés de pyrrolo-[2,3-d]pyrimidine en tant qu'inhibiteurs des kinases associées à la tropomyosine
EP2518071A1 (fr) 2011-04-29 2012-10-31 Almirall, S.A. Dérivés d'imidazopyridine en tant qu'inhibiteurs PI3K
EP2518070A1 (fr) 2011-04-29 2012-10-31 Almirall, S.A. Dérivés de pyrrolotriazinon en tant qu'inhibiteurs PI3K
WO2012157288A1 (fr) 2011-05-18 2012-11-22 Raqualia Pharma Inc. Forme polymorphe de l'acide 4-{[4-({[4-(2,2,2-trifluoroéthoxy)- 1,2-benzisoxazol-3-yl]oxy}méthyl)pipéridin-1-yl]méthyl}-tétrahydro-2h- pyran-4-carboxylique
EP2526945A1 (fr) 2011-05-25 2012-11-28 Almirall, S.A. Nouveaux antagonistes de CRTH2
EP2527344A1 (fr) 2011-05-25 2012-11-28 Almirall, S.A. Dérivés de pyridin-2(1h)-one utiles comme médicaments pour le traitement de maladies myeloproliferatives, de rejets de greffe, de maladies a médiation immune et de maladies inflammatoires
EP2548863A1 (fr) 2011-07-18 2013-01-23 Almirall, S.A. Nouveaux antagonistes de CRTH2
EP2548876A1 (fr) 2011-07-18 2013-01-23 Almirall, S.A. Nouveaux antagonistes de CRTH2
WO2013014567A1 (fr) 2011-07-27 2013-01-31 Pfizer Limited Indazoles
EP2554544A1 (fr) 2011-08-01 2013-02-06 Almirall, S.A. Dérivés de pyridin-2(1h)-one en tant qu'inhibiteurs de JAK
WO2013017989A1 (fr) 2011-08-02 2013-02-07 Pfizer Inc. Crizotinib pour l'utlisation dans le traitement de cancer
RU2476076C2 (ru) * 2007-02-26 2013-02-27 Револимер Лимитед Лечебная жевательная резинка
WO2013054185A1 (fr) 2011-10-13 2013-04-18 Pfizer, Inc. Dérivés de pyrimidine et de pyridine utiles en thérapie
WO2013057722A1 (fr) 2011-10-21 2013-04-25 Pfizer Limited Nouveau sel, et utilisation médicale
WO2013061297A1 (fr) 2011-10-28 2013-05-02 Pfizer Limited Dérivés de pyridazine utiles en thérapie
WO2013061205A2 (fr) 2011-10-26 2013-05-02 Pfizer Limited Composés chimiques
US8466166B2 (en) 2006-09-21 2013-06-18 Raqualia Pharma Inc. Benzimidazole derivatives as selective acid pump inhibitors
WO2013088315A1 (fr) 2011-12-15 2013-06-20 Pfizer Limited Dérivés de sulfonamide
WO2013093688A1 (fr) 2011-12-19 2013-06-27 Pfizer Limited Dérivés sulfonamides et leur utilisation en tant qu'inhibiteurs de vgsc
WO2013102826A1 (fr) 2012-01-04 2013-07-11 Pfizer Limited N-aminosulfonylbenzamides
WO2013114250A1 (fr) 2012-02-03 2013-08-08 Pfizer Inc. Dérivés d'imidazopyridine et de benziimidazole en tant que modulateurs du canal sodium
US8518952B2 (en) 2008-08-06 2013-08-27 Pfizer Inc. 6 substituted 2-heterocyclylamino pyrazine compounds as CHK-1 inhibitors
WO2013132376A1 (fr) 2012-03-06 2013-09-12 Pfizer Inc. Dérivés macrocycliques pour le traitement de maladies prolifératives
US8592403B2 (en) 2008-08-06 2013-11-26 Pfizer Limited Diazepine and diazocane compounds as MC4 agonists
WO2014049488A1 (fr) 2012-09-28 2014-04-03 Pfizer Inc. Composés de benzamide et hétérobenzamide
WO2014053967A1 (fr) 2012-10-04 2014-04-10 Pfizer Limited Inhibiteurs de kinase associée à la tropomyosine pyrrolo[2,3-d]pyrimidine
WO2014053968A1 (fr) 2012-10-04 2014-04-10 Pfizer Limited Inhibiteurs de kinase associée à la tropomyosine pyrrolo[3,2-c]pyridine
WO2014053965A1 (fr) 2012-10-04 2014-04-10 Pfizer Limited Inhibiteurs de kinases apparentés à la tropomyosine
WO2014060431A1 (fr) 2012-10-16 2014-04-24 Almirall, S.A. Dérivés de pyrrolotriazinone en tant qu'inhibiteurs des pi3k
WO2014072881A1 (fr) 2012-11-08 2014-05-15 Pfizer Inc. Composés hétéroaromatiques et leur utilisation comme ligands de la dopamine d1
WO2014072882A1 (fr) 2012-11-08 2014-05-15 Pfizer Inc. Composés hétéroaromatiques utilisés comme ligands de la dopamine d1
WO2014087298A1 (fr) 2012-12-03 2014-06-12 Pfizer Inc. Nouveaux modulateurs androgéniques sélectifs
WO2014091368A1 (fr) 2012-12-14 2014-06-19 Pfizer Limited Dérivés d'imidazopyridazine en tant que modulateurs d'un récepteur gabaa
WO2014097041A1 (fr) 2012-12-21 2014-06-26 Pfizer Inc. Lactames fusionnés à un aryle et hétéroaryle
US8771643B2 (en) 2008-01-04 2014-07-08 Schabar Research Associates Llc Use of analgesic potentiating compounds to potentiate the analgesic properties of an analgesic compound
WO2014124757A1 (fr) 2013-02-15 2014-08-21 Almirall, S.A. Dérivés de pyrrolotriazinone utilisés en tant qu'inhibiteurs de pi3k
WO2014128588A1 (fr) 2013-02-21 2014-08-28 Pfizer Inc. Formes solides d'un inhibiteur sélectif de cdk4/6
EP2792360A1 (fr) 2013-04-18 2014-10-22 IP Gesellschaft für Management mbH (1aR,12bS)-8-cyclohexyl-11-fluoro-N-((1-methylcyclopropyl)sulfonyl)-1a-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-1,1a,2,2b-tetrahydrocyclopropa[d]indolo[2,1-a][2]benzazepine-5-carboxamide pour utilisation dans le traitement de HCV
WO2014170792A1 (fr) 2013-04-19 2014-10-23 Pfizer Limited Dérivés sulfonamides utilisés comme inhibiteurs de l'urat-1
WO2014170793A1 (fr) 2013-04-19 2014-10-23 Pfizer Limited Sulfonamides pour le traitement de la goutte
WO2014181213A1 (fr) 2013-05-10 2014-11-13 Pfizer Inc. Forme cristalline de (sa)-(-)-3-(3-bromo-4-((2,4-difluorobenzyl)oxy)-6-methyl-2-oxopyridin-1 (2h)-yl)-n,4-dimethylbenzamide
WO2014186742A2 (fr) 2013-05-17 2014-11-20 Acupac Packaging, Inc. Composition d'hydrogel anhydre
WO2014207601A1 (fr) 2013-06-27 2014-12-31 Pfizer Inc. Composés hétéro-aromatiques et leur utilisation en tant que ligands d1 de la dopamine
WO2015050989A2 (fr) 2013-10-01 2015-04-09 Cs Therapeutics Inc. Composés macrocycliques destinés au traitement de maladies prolifératives
US9011946B2 (en) 2011-04-29 2015-04-21 Intercontinental Great Brands Llc Encapsulated acid, method for the preparation thereof, and chewing gum comprising same
WO2015092610A1 (fr) 2013-12-20 2015-06-25 Pfizer Limited Inhibiteurs de kinase apparentés à la n-acylpipéridine éther tropomyosine
WO2015092614A1 (fr) 2013-12-20 2015-06-25 Pfizer Inc. Altérations d'activation de notch dans le cancer du sein
KR20150085515A (ko) 2012-11-21 2015-07-23 라퀄리아 파마 인코포레이티드 다형체
WO2015159175A1 (fr) 2014-04-15 2015-10-22 Pfizer Inc. Inhibiteurs de kinases apparentées à la tropomyosine contenant à la fois un 1h-pyrazole et un fragment pyrimidine
WO2015162516A1 (fr) 2014-04-25 2015-10-29 Pfizer Inc. Composés hétéroaromatiques et leur utilisation comme ligands de la dopamine d1
WO2015162515A1 (fr) 2014-04-25 2015-10-29 Pfizer Inc. Composés hétéroaromatiques et leur utilisation comme ligands de la dopamine d1
WO2015162518A1 (fr) 2014-04-25 2015-10-29 Pfizer Inc. Composes hetero-aromatiques et leur utilisation comme ligands d1 de la dopamine
WO2015166370A1 (fr) 2014-04-28 2015-11-05 Pfizer Inc. Composés hétéroaromatiques et leur utilisation en tant que ligands de la dopamine d1
WO2015166366A1 (fr) 2014-04-28 2015-11-05 Pfizer Inc. Composés hétérocycliques et leur utilisation comme ligands des récepteurs d1 de la dopamine
WO2015170218A1 (fr) 2014-05-07 2015-11-12 Pfizer Inc. Inhibiteurs de kinases apparentées à la tropomyosine
WO2015173684A1 (fr) 2014-05-15 2015-11-19 Pfizer Inc. Forme cristalline du 6-[(4r)-4-méthyl -1,2-dioxydo-1,2,6-thiadiazinan -2-yle]isoquinoline-1-carbonitrile
WO2015173683A1 (fr) 2014-05-14 2015-11-19 Pfizer Inc. Pyrazolopyridines et pyrazolopyrimidines
US9198448B2 (en) 2005-02-07 2015-12-01 Intercontinental Great Brands Llc Stable tooth whitening gum with reactive ingredients
WO2015181797A1 (fr) 2014-05-30 2015-12-03 Pfizer Inc. Benzènesulfonamides utiles en tant qu'inhibiteurs des canaux sodiques
WO2015181676A1 (fr) 2014-05-30 2015-12-03 Pfizer Inc. Dérivés carbonitriles en tant que modulateurs sélectifs du récepteur des androgènes
WO2015189744A1 (fr) 2014-06-12 2015-12-17 Pfizer Limited Dérivés d'imidazopyridazine utilisés comme modulateurs de l'activité des récepteurs gabaa.
WO2015193765A1 (fr) 2014-06-17 2015-12-23 Pfizer Inc. Composés dihydroisoquinolinone substitués
WO2015193768A1 (fr) 2014-06-17 2015-12-23 Pfizer Inc. Lactames à fusion aryle à utiliser en tant que modulateurs ezh2
WO2016009296A1 (fr) 2014-07-16 2016-01-21 Pfizer Inc. Inhibiteurs de kinase liés à la n-acylpipéridine éther tropomyosine
WO2016009297A1 (fr) 2014-07-18 2016-01-21 Pfizer Inc. Dérivés de la pyridine en tant que modulateurs allostériques positifs du récepteur m1 muscarinique
WO2016009303A1 (fr) 2014-07-17 2016-01-21 Pfizer Inc. Associations de produits pharmaceutiques comprenant de la gabapentine ou de la prégabaline avec des inhibiteurs de nav1.7
WO2016020784A1 (fr) 2014-08-05 2016-02-11 Pfizer Inc. Inhibiteurs de kinases apparentées à la n-acylpyrrolidine éther tropomyosine
WO2016034971A1 (fr) 2014-09-04 2016-03-10 Pfizer Limited Dérivés sulfonamides utilisés en tant qu'inhibiteurs d'urat1
WO2016044433A2 (fr) 2014-09-16 2016-03-24 Biopharma Works Dérivés de la metformine
WO2016067143A1 (fr) 2014-10-28 2016-05-06 Pfizer Inc. Composés n- (2-alkylèneimino-3-phénylpropyl)acétamide et leur utilisation contre la douleur et le prurit par inhibition des canaux trpa1
WO2016072854A2 (fr) 2014-11-06 2016-05-12 Radboud Universitair Medisch Centrum Analogues de pantothénamide
WO2016097918A1 (fr) 2014-12-18 2016-06-23 Pfizer Inc. Dérivés de pyrimidine et de triazine, et leur utilisation comme inhibiteurs d'axl
WO2016116628A1 (fr) 2015-01-22 2016-07-28 Phytoplant Research S.L. Procédés de purification de cannabinoïdes, compositions de cannabinoïdes et trousses associées
WO2016170009A1 (fr) 2015-04-21 2016-10-27 Almirall, S.A. Dérivés hétérocycliques amino-substitués utilisés comme inhibiteurs des canaux sodiques
US9533989B2 (en) 2012-09-18 2017-01-03 Ziarco Pharma Ltd. Substituted pyrimidine-5-carboxamides as spleen tyrosine kinase inhibitors
WO2017021805A1 (fr) 2015-07-31 2017-02-09 Pfizer Inc. Dérivés de carbamate de 1,1,1-trifluoro-3-hydroxypropan-2-yle et dérivés de carbamate de 1,1,1-trifluoro-4-hydroxybutan-2-yle comme inhibiteurs de magl
WO2017060488A1 (fr) 2015-10-09 2017-04-13 Almirall, S.A. Nouveaux antagonistes de trpa1
WO2017064068A1 (fr) 2015-10-14 2017-04-20 Almirall, S.A. Nouveaux antagonistes de trpa1
WO2017098367A1 (fr) 2015-12-10 2017-06-15 Pfizer Limited Dérivés 4-(biphényl-3-yl)-1h-pyrazolo[3,4-c]pyridazine de formule (i) utilisés comme modulateurs de récepteur gaba pour le traitement de l'épilepsie et de la douleur
WO2017100784A1 (fr) * 2015-12-11 2017-06-15 Wm. Wrigley Jr. Company Formulations à indicateur de couleur
WO2017120429A1 (fr) 2016-01-07 2017-07-13 CS Pharmasciences, Inc. Inhibiteurs sélectifs de mutants cliniquement importants de la tyrosine kinase de l'egfr
WO2017119732A1 (fr) 2016-01-08 2017-07-13 Samsung Electronics Co., Ltd. Dispositif électronique, et son procédé de fonctionnement
WO2017122116A1 (fr) 2016-01-15 2017-07-20 Pfizer Inc. Ligands 6,7,8,9-tétrahydro-5h-pyrido[2,3-d]azépine du récepteur d3 de la dopamine
WO2017156341A1 (fr) 2016-03-09 2017-09-14 Beijing Percans Oncology Co. Ltd. Cultures en suspension de cellules tumorales et procédés associés
WO2017212385A1 (fr) 2016-06-06 2017-12-14 Pfizer Inc. Dérivés de carbonucléosides substitués utiles en tant qu'agents anticancéreux
WO2018033815A1 (fr) 2016-08-15 2018-02-22 Pfizer Inc. Inhibiteurs de pyridopyrimidinone cdk2/4/6
US9956211B2 (en) 2011-04-29 2018-05-01 Moberg Pharma Ab Pharmaceutical compositions comprising a local anaesthetic such as bupivacaine for local administration to the mouth or throat
WO2018096510A1 (fr) 2016-11-28 2018-05-31 Pfizer Inc. Ligands opioïdes kappa hétéroarylphénoxy benzamide
US9988370B2 (en) 2014-05-20 2018-06-05 Raqualia Pharma Inc. Benzisoxazole derivative salt
WO2018134695A1 (fr) 2017-01-20 2018-07-26 Pfizer Inc. Dérivés de 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate utilisés comme inhibiteurs de la magl
WO2018134698A1 (fr) 2017-01-23 2018-07-26 Pfizer Inc. Composés spiro hétérocycliques utilisés en tant qu'inhibiteurs de magl
WO2018138591A1 (fr) 2017-01-24 2018-08-02 Pfizer Inc. Dérivés de calichéamicine et conjugués anticorps-médicaments de ceux-ci
WO2018219650A1 (fr) 2017-05-30 2018-12-06 Enorama Pharma Ab Compositions de gomme à mâcher contenant de la nicotine
WO2019051469A1 (fr) 2017-09-11 2019-03-14 Krouzon Pharmaceuticals, Inc. Inhibiteurs allostériques octahydrocyclopenta[c]pyrrole de shp2
WO2019097369A1 (fr) 2017-11-14 2019-05-23 Pfizer Inc. Polythérapies faisant appel à un inhibiteur de ezh2
WO2019145552A1 (fr) 2018-01-29 2019-08-01 Phytoplant Research S.L Procédés de purification de cannabinoïdes par chromatographie liquide : liquide
WO2019150305A1 (fr) 2018-02-01 2019-08-08 Pfizer Inc. Dérivés de quinazoline et de pyridopyrimidine substitués utiles en tant qu'agents anticancéreux
WO2019155399A1 (fr) 2018-02-09 2019-08-15 Pfizer Inc. Dérivés de tétrahydroquinazoline utiles en tant qu'agents anticancéreux
WO2019166928A1 (fr) 2018-02-27 2019-09-06 Pfizer Inc. Association d'un inhibiteur de kinases dépendantes des cyclines et d'un inhibiteur de bromodomaines bet
US10428104B2 (en) 2015-02-24 2019-10-01 Pfizer Inc. Substituted nucleoside derivatives useful as anticancer agents
WO2019207463A1 (fr) 2018-04-26 2019-10-31 Pfizer Inc. Dérivés de 2-amino-pyridine ou de 2-amino-pyrimidine utilisés en tant qu'inhibiteurs de kinases dépendantes des cyclines
WO2019243823A1 (fr) 2018-06-21 2019-12-26 Curadev Pharma Limited Modulateurs azahétérocycliques à petites molécules de sting humain
WO2020016710A1 (fr) 2018-07-19 2020-01-23 Pfizer Inc. Composés spiro hétérocycliques utilisés en tant qu'inhibiteurs de magl
US10624972B2 (en) 2015-03-13 2020-04-21 Endocyte, Inc. Conjugates for treating diseases
WO2020100027A1 (fr) 2018-11-15 2020-05-22 Pfizer Inc. Dérivés de 2,3-dihydro-1h-pyrrolo[3,4-c]pyridin-1-one servant d'inhibiteurs de hpk1 pour le traitement du cancer
EP3674288A1 (fr) 2018-12-31 2020-07-01 MMV Medicines for Malaria Venture Analogues de pantothénamide
WO2020152557A1 (fr) 2019-01-23 2020-07-30 Pfizer Inc. Forme polymorphe d'un sel d'hydrate de monophosphate d'un dérivé de tétrahydroisoquinoline connu
WO2020157709A1 (fr) 2019-02-01 2020-08-06 Pfizer Inc. Association d'un inhibiteur de cdk et d'un inhibiteur de pim
WO2020157652A2 (fr) 2019-01-31 2020-08-06 Pfizer Inc. Inhibiteurs de cdk2
US10793572B2 (en) 2014-09-29 2020-10-06 The Provost Fellows Foundation Scholars And The Other Members Of Board Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Substituted pyrimidine derivatives useful in the treatment of autoimmune diseases
WO2021009676A1 (fr) 2019-07-17 2021-01-21 Pfizer Inc. Dérivés d'imidazo [4,5-c] pyridine en tant qu'agonistes du récepteur de type toll
WO2021014415A2 (fr) 2019-07-25 2021-01-28 Curadev Pharma Pvt. Ltd. Inhibiteurs à petites molécules de l'acétyl-coenzyme a synthétase à chaîne courte 2 (acss2)
GB202104609D0 (en) 2021-03-31 2021-05-12 Sevenless Therapeutics Ltd New Treatments for Pain
WO2021161230A1 (fr) 2020-02-12 2021-08-19 Curadev Pharma Pvt. Ltd. Antagonistes de sting à petites molécules
WO2021176349A1 (fr) 2020-03-05 2021-09-10 Pfizer Inc. Combinaison d'un inhibiteur de kinase du lymphome anaplasique et d'un inhibiteur de kinase dépendant de la cycline
WO2021205363A1 (fr) 2020-04-08 2021-10-14 Pfizer Inc. Co-traitement avec des inhibiteurs de cdk4/6 et de cdk2 pour supprimer l'adaptation tumorale à des inhibiteurs de cdk2
WO2021220185A1 (fr) 2020-05-01 2021-11-04 Pfizer Inc. Composés d'azalactame utilisé en tant qu'inhibiteurs de hpk1
WO2021224818A1 (fr) 2020-05-08 2021-11-11 Pfizer Inc. Composés d'isoindolone en tant qu'inhibiteurs de hpk1
WO2022003575A1 (fr) 2020-06-30 2022-01-06 Array Biopharma Inc. Inhibiteurs de mutation her2
WO2022013691A1 (fr) 2020-07-15 2022-01-20 Pfizer Inc. Polymorphe de (1s,2s,3s,5r)-3-((6-(difluorométhyl)-5-flu­oro-1,2,3,4-tétrahydroisoquinolin-8-yl)oxy)-5-(4-méthyl-7h-pyrrolo[2,3-d]­pyrimidin-7-yl)cyclopentane-1,2-diol
WO2022013692A1 (fr) 2020-07-15 2022-01-20 Pfizer Inc. Polymorphes de (1s,2s,3s,5r)-3-((6-(difluorométhyl)-3-((6-(difluorométhyl)-5-fluoro-1,2,3,4-tétrahydroisoquinolin-8-yl)oxy)-5-(4-méthyl-7h-pyrrolo[2,3-d]pyrimidin-7-yl) cyclopentane-1,2-diol monochlorhydrate
US11229652B2 (en) 2014-09-29 2022-01-25 The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin Treatments for autoimmune disease
WO2022018667A1 (fr) 2020-07-24 2022-01-27 Pfizer Inc. Polythérapies utilisant des inhibiteurs de cdk2 et de cdc25a
WO2022018596A1 (fr) 2020-07-20 2022-01-27 Pfizer Inc. Polythérapie
WO2022023438A1 (fr) 2020-07-29 2022-02-03 The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin Composés
WO2022023433A1 (fr) 2020-07-29 2022-02-03 The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin Composés
WO2022034504A1 (fr) 2020-08-13 2022-02-17 Pfizer Inc. Polythérapie
WO2022058871A1 (fr) 2020-09-15 2022-03-24 Pfizer Inc. Formes solides d'un inhibiteur de cdk4
US11324727B2 (en) 2020-07-15 2022-05-10 Schabar Research Associates, Llc Unit oral dose compositions composed of naproxen sodium and famotidine for the treatment of acute pain and the reduction of the severity of heartburn and/or the risk of heartburn
US11331307B2 (en) 2020-07-15 2022-05-17 Schabar Research Associates, Llc Unit oral dose compositions composed of ibuprofen and famotidine for the treatment of acute pain and the reduction of the severity and/or risk of heartburn
WO2022137106A1 (fr) 2020-12-24 2022-06-30 Pfizer Inc. Formes solides d'un inhibiteur de cdk2
WO2022137174A1 (fr) 2020-12-22 2022-06-30 Pfizer Inc. Formes solides d'un inhibiteur de eif4e
WO2022195462A1 (fr) 2021-03-18 2022-09-22 Pfizer Inc. Modulateurs de sting (stimulateur des gènes de l'interféron)
WO2022200982A1 (fr) 2021-03-24 2022-09-29 Pfizer Inc. Combinaison de talazoparib et d'un anti-androgène pour le traitement du cancer de la prostate métastatique sensible à la castration et muté par le gène ddr
WO2022207673A1 (fr) 2021-03-31 2022-10-06 Sevenless Therapeutics Limited Inhibiteurs de sos1 et inhibiteurs de ras destinés à être utilisés dans le traitement de la douleur
WO2022214869A2 (fr) 2021-04-07 2022-10-13 Lifearc Inhibiteurs ulk1/2 et leur utilisation
WO2022229846A1 (fr) 2021-04-29 2022-11-03 Pfizer Inc. Traitement du cancer à l'aide d'un inhibiteur du récepteur du facteur de croissance transformant bêta de type 1
WO2022269531A1 (fr) 2021-06-26 2022-12-29 Array Biopharma Inc. Inhibiteurs de mutation her2
WO2023002362A1 (fr) 2021-07-22 2023-01-26 Pfizer Inc. Traitement d'une malignité hématologique
US11571423B2 (en) 2017-06-22 2023-02-07 Curadev Pharma Limited Small molecule modulators of human sting
WO2023017451A1 (fr) 2021-08-11 2023-02-16 Curadev Pharma Pvt. Ltd. Antagonistes de sting à petites molécules
WO2023017452A1 (fr) 2021-08-11 2023-02-16 Curadev Pharma Pvt. Ltd. Dérivés d'urée à petites molécules en tant qu'antagonistes de sting
WO2023084459A1 (fr) 2021-11-15 2023-05-19 Pfizer Inc. Méthodes de traitement du sars-cov-2
WO2023099072A1 (fr) 2021-12-01 2023-06-08 Fundación Del Sector Público Estatal Centro Nacional De Investigaciones Oncológicas Carlos III (F.S.P. CNIO) Composés
WO2023100134A1 (fr) 2021-12-02 2023-06-08 Pfizer Inc. Méthodes et schémas posologiques comprenant un inhibiteur de cdk2 et un inhibiteur de cdk4 pour le traitement du cancer
US11773132B2 (en) 2017-08-30 2023-10-03 Beijing Xuanyi Pharmasciences Co., Ltd. Cyclic di-nucleotides as stimulator of interferon genes modulators
EP4252856A2 (fr) 2016-12-20 2023-10-04 Oligomerix, Inc. Nouvelles quinazolinones inhibant la formation d'oligomères tau et leur procédé d'utilisation
WO2024023727A1 (fr) 2022-07-29 2024-02-01 Pfizer Inc. Nouveaux inhibiteurs de l'acc
WO2024033513A1 (fr) 2022-08-11 2024-02-15 Diaccurate Composés pour le traitement du cancer
WO2024074827A1 (fr) 2022-10-05 2024-04-11 Sevenless Therapeutics Limited Nouveaux traitements de la douleur

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6531114B1 (en) * 1999-04-06 2003-03-11 Wm. Wrigley Jr. Company Sildenafil citrate chewing gum formulations and methods of using the same
US6322806B1 (en) * 1999-04-06 2001-11-27 Wm. Wrigley Jr. Company Over-coated chewing gum formulations including tableted center
US6541048B2 (en) * 1999-09-02 2003-04-01 Wm. Wrigley Jr. Company Coated chewing gum products containing an acid blocker and process of preparing
US6645535B2 (en) * 1999-09-02 2003-11-11 Wm. Wrigley Jr. Company Method of making coated chewing gum products containing various antacids
US6663849B1 (en) 2000-09-01 2003-12-16 Wm. Wrigley Jr. Company Antacid chewing gum products coated with high viscosity materials
US6569472B1 (en) * 2000-09-01 2003-05-27 Wm. Wrigley Jr. Company Coated chewing gum products containing antacid and method of making
DE10013712A1 (de) * 2000-03-20 2001-09-27 Nutrinova Gmbh Nikotinsalze mit verbessertem Geschmack, Verfahren zu ihrer Herstellung und ihre Verwendung
WO2002013781A1 (fr) * 2000-08-14 2002-02-21 Fertin Pharma A/S Procede de preparation d'une gomme a macher ayant un gout agreable pour le consommateur
US6579545B2 (en) * 2000-12-22 2003-06-17 Wm. Wrigley Jr. Company Coated chewing gum products containing an antigas agent
US7087255B2 (en) 2000-12-27 2006-08-08 Wm. Wrigley Jr. Company Chewing gums that provide breath freshening characteristics
DE60230020D1 (de) * 2001-03-23 2009-01-08 Gumlinck As Beschichteter, abbaubarer kaugummi mit verbesserter haltbarkeit sowie verfahren zu seiner herstellung
EP1922937A3 (fr) * 2001-03-23 2008-06-04 Gumlink A/S Gomme à mâcher enrobée dégradable dotée d'une durée de vie améliorée et son procédé de fabrication.
US20030035839A1 (en) * 2001-05-15 2003-02-20 Peirce Management, Llc Pharmaceutical composition for both intraoral and oral administration
SE0102197D0 (sv) * 2001-06-20 2001-06-20 Pharmacia Ab New product and use and manufacture thereof
US6863901B2 (en) 2001-11-30 2005-03-08 Collegium Pharmaceutical, Inc. Pharmaceutical composition for compressed annular tablet with molded triturate tablet for both intraoral and oral administration
US6827946B2 (en) 2001-12-05 2004-12-07 Collegium Pharmaceutical, Inc. Compositions containing both sedative and non-sedative antihistamines
AU2003209750A1 (en) * 2002-03-30 2003-10-13 Gunther Beisel Preparation containing fatty acid, used for reducing appetite, satiating, and/or reducing weight
US7767698B2 (en) 2002-06-03 2010-08-03 Mcneil Ab Formulation and use thereof
CA2500022C (fr) 2002-09-24 2011-02-22 Gumlink A/S Gomme a macher biodegradable comprenant au moins un polymere biodegradable de poids moleculaire eleve
JP2006500041A (ja) 2002-09-24 2006-01-05 ガムリンク エー／エス 少なくとも２種類の異なる生分解性ポリマーを含有するチューインガム
DE10300187B4 (de) * 2003-01-08 2007-03-29 Cognis Ip Management Gmbh Kaugummizusammensetzung mit pflanzlichen Wirkstoffen
US9271904B2 (en) 2003-11-21 2016-03-01 Intercontinental Great Brands Llc Controlled release oral delivery systems
DK1765304T4 (da) 2004-07-06 2019-06-03 Fertin Pharma As Komprimattyggegummitablet
KR102060738B1 (ko) * 2012-12-13 2019-12-30 한미약품 주식회사 에스오메프라졸 유리염기 또는 그의 알칼리염을 포함하는 고미가 차폐된 약학 제제 및 이의 제조방법
US20200178557A1 (en) * 2017-08-18 2020-06-11 Intercontinental Great Brands Llc Chewing gum compositions and methods of making thereof

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4452821A (en) * 1981-12-18 1984-06-05 Gerhard Gergely Confectionery product, particularly chewing gum, and process for its manufacture
US4639368A (en) * 1984-08-23 1987-01-27 Farmacon Research Corporation Chewing gum containing a medicament and taste maskers
US4753805A (en) * 1984-01-31 1988-06-28 Warner-Lambert Company Tabletted chewing gum composition and method of preparation
US4978537A (en) * 1989-04-19 1990-12-18 Wm. Wrigley Jr. Company Gradual release structures for chewing gum
US4997659A (en) * 1989-03-28 1991-03-05 The Wm. Wrigley Jr. Company Alitame stability in chewing gum by encapsulation
US5013716A (en) * 1988-10-28 1991-05-07 Warner-Lambert Company Unpleasant taste masking compositions and methods for preparing same
US5433960A (en) * 1992-04-21 1995-07-18 Wm. Wrigley Jr. Company Chewing gum including agent containing edible film
WO1998023165A1 (fr) * 1996-11-27 1998-06-04 Wm. Wrigley Jr. Company Procede permettant de reguler la liberation de cafeine dans de la gomme a macher et gomme ainsi produite
US5846557A (en) * 1996-03-20 1998-12-08 Cumberland Packing Corporation Chewing gum containing cough suppressing agent

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4452821A (en) * 1981-12-18 1984-06-05 Gerhard Gergely Confectionery product, particularly chewing gum, and process for its manufacture
US4753805A (en) * 1984-01-31 1988-06-28 Warner-Lambert Company Tabletted chewing gum composition and method of preparation
US4639368A (en) * 1984-08-23 1987-01-27 Farmacon Research Corporation Chewing gum containing a medicament and taste maskers
US5013716A (en) * 1988-10-28 1991-05-07 Warner-Lambert Company Unpleasant taste masking compositions and methods for preparing same
US4997659A (en) * 1989-03-28 1991-03-05 The Wm. Wrigley Jr. Company Alitame stability in chewing gum by encapsulation
US4978537A (en) * 1989-04-19 1990-12-18 Wm. Wrigley Jr. Company Gradual release structures for chewing gum
US5433960A (en) * 1992-04-21 1995-07-18 Wm. Wrigley Jr. Company Chewing gum including agent containing edible film
US5846557A (en) * 1996-03-20 1998-12-08 Cumberland Packing Corporation Chewing gum containing cough suppressing agent
WO1998023165A1 (fr) * 1996-11-27 1998-06-04 Wm. Wrigley Jr. Company Procede permettant de reguler la liberation de cafeine dans de la gomme a macher et gomme ainsi produite

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1221863A4 *

Cited By (307)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7078052B2 (en) 1999-04-06 2006-07-18 Wm. Wrigley Jr. Company Pharmaceutical chewing gum formulations
US6485739B2 (en) 2000-03-10 2002-11-26 Warner-Lambert Company Stain removing chewing gum and confectionery compositions, and methods of making and using the same
US6696044B2 (en) 2000-03-10 2004-02-24 Cadbury Adams Usa Llc Stain removing chewing gum and confectionery compositions, and methods of making and using the same
US6471945B2 (en) 2000-03-10 2002-10-29 Warner-Lambert Company Stain removing chewing gum and confectionery compositions, and methods of making and using the same
US8946229B2 (en) 2002-01-15 2015-02-03 Ucb, Inc. Formulations
EP1467715B1 (fr) * 2002-01-15 2010-11-03 Ucb Farchim S.A. Formulations pour l'adminstration orale de composes actifs
EP1467715A1 (fr) 2002-01-15 2004-10-20 UCB Farchim S.A. Formulations pour l'adminstration orale de composes actifs
EP2196201A2 (fr) 2002-12-13 2010-06-16 Warner-Lambert Company LLC Combinaison d'un ligand alpha-2-delta avec un inhibiteur de pdev ou avec un antagoniste muscarinique pour traiter les symptomes des voies urinaires inferieures
US7268147B2 (en) 2003-05-15 2007-09-11 Pfizer Inc Compounds useful for the treatment of diseases
US7776885B2 (en) 2003-09-03 2010-08-17 Pfizer, Inc. Benzimidazolone compounds having 5-HT4 receptor agonistic activity
US7790740B2 (en) 2003-10-03 2010-09-07 Pfizer Inc Imidazopyridine substituted tropane derivatives with CCR5 receptor antagonist activity for the treatment of HIV and inflammation
US7309790B2 (en) 2003-10-03 2007-12-18 Pfizer Inc Chemical compounds
US7649002B2 (en) 2004-02-04 2010-01-19 Pfizer Inc (3,5-dimethylpiperidin-1yl)(4-phenylpyrrolidin-3-yl)methanone derivatives as MCR4 agonists
US7629358B2 (en) 2004-03-17 2009-12-08 Pfizer Inc Compounds useful for the treatment of diseases
US7241810B2 (en) 2004-03-23 2007-07-10 Pfizer Inc Formamide derivatives for the treatment of diseases
US7538141B2 (en) 2004-03-23 2009-05-26 Alan Daniel Brown Compounds for the treatment of diseases
US7547731B2 (en) 2004-03-23 2009-06-16 Pfizer Inc Formamide derivatives for the treatment of diseases
US7456164B2 (en) 2004-05-07 2008-11-25 Pfizer, Inc 3- or 4-monosubtituted phenol and thiophenol derivatives useful as H3 ligands
US7557121B2 (en) 2004-05-12 2009-07-07 Pfizer Inc Tetrahydronaphthyridine derivatives
US7595329B2 (en) 2004-06-15 2009-09-29 Pfizer Inc Benzimidazolone carboxylic acid derivatives
US7737163B2 (en) 2004-06-15 2010-06-15 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
US7705020B2 (en) 2004-06-15 2010-04-27 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
US8076356B2 (en) 2004-08-12 2011-12-13 Pfizer Inc. Triazolopyridinylsulfanyl derivatives as P38 map kinase inhibitors
US7511057B2 (en) 2004-08-12 2009-03-31 Pfizer Inc. Triazolopyridinylsulfanyl derivatives as p38 MAP kinase inhibitors
US8211980B2 (en) 2004-08-12 2012-07-03 Revolymer Limited Polymeric materials having reduced tack, methods of making the materials and chewing gum compositions containing such materials
US20100136164A1 (en) * 2004-08-25 2010-06-03 Cadbury Adams Usa Llc Package assembly for multi-modality taste chewing gum compositions
US20080014302A1 (en) * 2004-08-25 2008-01-17 Cadbury Adams Usa Llc Multi-region chewing gum composition including isomalt gum region
US7727565B2 (en) 2004-08-25 2010-06-01 Cadbury Adams Usa Llc Liquid-filled chewing gum composition
US20100203191A1 (en) * 2004-08-25 2010-08-12 Cadbury Adams Usa Llc Liquid-filled chewing gum composition
US8785632B2 (en) 2004-08-26 2014-07-22 Agouron Pharmaceuticals, Inc. Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
US7858643B2 (en) 2004-08-26 2010-12-28 Agouron Pharmaceuticals, Inc. Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
US7598393B2 (en) 2004-11-02 2009-10-06 Pfizer Inc. Sulfonyl benzimidazole derivatives
US9198448B2 (en) 2005-02-07 2015-12-01 Intercontinental Great Brands Llc Stable tooth whitening gum with reactive ingredients
WO2006090388A2 (fr) 2005-02-25 2006-08-31 The State Of Israel, Ministry Of Agriculture & Rural Development, Agricultural Research Organization, (A.R.O.), Volcani Center Composition pour administration par les muqueuses de cultures de cellules de fruit et de preparations tirees de ces cultures, et methodes de fabrication
US8216801B2 (en) 2005-02-25 2012-07-10 The State Of Israel, Ministry Of Agriculture & Rural Development, Agricultural Research Organization, (A.R.O.), The Volcani Center Methods for treating inflammatory disorders
WO2006097817A1 (fr) 2005-03-17 2006-09-21 Pfizer Japan Inc. Derives de n-(n-sulfonylaminomethyl)cyclopropanecarboxamide utilises pour traiter une douleur
US7618972B2 (en) 2005-03-21 2009-11-17 Pfizer Inc Substituted triazole derivatives as oxytocin antagonists
US7642350B2 (en) 2005-05-04 2010-01-05 Pfizer Limited Purine derivatives
WO2006124366A2 (fr) 2005-05-18 2006-11-23 Mcneil-Ppc, Inc. Aromatisant pour chewing gums contenant un medicament
WO2006124366A3 (fr) * 2005-05-18 2007-01-25 Warner Lambert Co Aromatisant pour chewing gums contenant un medicament
US8323683B2 (en) 2005-05-18 2012-12-04 Mcneil-Ppc, Inc. Flavoring of drug-containing chewing gums
US8658200B2 (en) 2005-05-18 2014-02-25 Mcneil-Ppc, Inc. Flavoring of drug-containing chewing gums
AU2006247847B2 (en) * 2005-05-18 2011-05-26 Warner-Lambert Company Llc Flavoring of drug-containing chewing gums
US7538134B2 (en) 2005-06-15 2009-05-26 Pfizer Inc. Substituted arylpyrazoles
US7968584B2 (en) 2005-06-15 2011-06-28 Pfizer Inc. Substituted arylpyrazoles
US7645786B2 (en) 2005-06-15 2010-01-12 Pfizer Inc. Substituted arylpyrazoles
EP2484768A2 (fr) 2005-07-18 2012-08-08 Protalix Ltd. Administration mucosale ou enterale de macromolecules biologiquement actives
EP2441840A1 (fr) 2005-07-18 2012-04-18 Protalix Ltd. Administration mucosale ou enterale de macromolecules biologiquement actives
WO2007072163A2 (fr) 2005-12-20 2007-06-28 Pfizer Limited Derives de pyrimidine
EP2017259A2 (fr) 2005-12-21 2009-01-21 Pfizer Products Inc. Preparation d'acides gamma-amines ayant une affinité pour la protéine alpha-2-delta
US8138188B2 (en) 2006-02-23 2012-03-20 Pfizer Inc. Melanocortin type 4 receptor agonist piperidinoylpyrrolidines
US8133476B2 (en) 2006-04-05 2012-03-13 Cadbury Adams Usa Llc Calcium phosphate complex and salts in oral delivery systems
US8252269B2 (en) 2006-04-05 2012-08-28 Cadbury Adams Usa, Llc Impact of calcium phosphate complex on dental caries
EP2258700A1 (fr) 2006-05-09 2010-12-08 Pfizer Products Inc. Dérivés d'acides aminés cycloalkyles et compositions pharmaceutiques les contenant
US8278355B2 (en) 2006-09-12 2012-10-02 Therexcell Pharma Inc. Isovaline for treatment of pain
US8466166B2 (en) 2006-09-21 2013-06-18 Raqualia Pharma Inc. Benzimidazole derivatives as selective acid pump inhibitors
EP2083633A1 (fr) * 2006-10-11 2009-08-05 WM. Wrigley Jr., Company Véhicules d'administration orale contenant un médicament traditionnel chinois ou un extrait de celui-ci
EP2083633A4 (fr) * 2006-10-11 2012-01-18 Wrigley W M Jun Co Véhicules d'administration orale contenant un médicament traditionnel chinois ou un extrait de celui-ci
WO2008050199A2 (fr) 2006-10-23 2008-05-02 Pfizer Japan Inc. Composés de phénylméthyl bicyclocarboxyamide substitués
WO2008104547A1 (fr) * 2007-02-26 2008-09-04 Revolymer Limited Gomme à mâcher médicamentée
JP2010518845A (ja) * 2007-02-26 2010-06-03 リヴォリマー リミテッド 薬用チューインガム
RU2476076C2 (ru) * 2007-02-26 2013-02-27 Револимер Лимитед Лечебная жевательная резинка
EP2246045A1 (fr) 2007-08-13 2010-11-03 McNeil-PPC, Inc. Procédé de stabilisation de phényléphrine
US9044465B2 (en) 2008-01-04 2015-06-02 Schabar Research Associates, Llc Use of analgesic potentiating compounds to potentiate the analgesic properties of an analgesic compound
US8771643B2 (en) 2008-01-04 2014-07-08 Schabar Research Associates Llc Use of analgesic potentiating compounds to potentiate the analgesic properties of an analgesic compound
US8592403B2 (en) 2008-08-06 2013-11-26 Pfizer Limited Diazepine and diazocane compounds as MC4 agonists
US8518952B2 (en) 2008-08-06 2013-08-27 Pfizer Inc. 6 substituted 2-heterocyclylamino pyrazine compounds as CHK-1 inhibitors
EP2163253A1 (fr) 2008-09-15 2010-03-17 Charité-Universitätsmedizin Berlin Extraits de la plante Hornstedtia scyphifera et ses effets immunosuppresseurs
WO2010058858A1 (fr) 2008-11-21 2010-05-27 ラクオリア創薬株式会社 Nouveau dérivé de pyrazole-3-carboxamide doté d’une activité antagoniste du récepteur 5-ht2b
WO2010079443A1 (fr) 2009-01-12 2010-07-15 Pfizer Limited Dérivés sulfonamides
WO2010103070A2 (fr) 2009-03-12 2010-09-16 Charité - Universitätsmedizin Berlin Variants de la protéine morphogénétique osseuse 2 (bmp2) avec une sensibilité réduite aux antagonistes des bmp
WO2010109010A1 (fr) 2009-03-27 2010-09-30 Deutsches Rheuma-Forschungszentrum Berlin (Drfz) Anticorps sialylés dirigés contre des antigènes spécifiques utilisés en traitement ou en prophylaxie de réactions immunitaires inflammatoires indésirables, et méthodes de production associées
EP2233502A1 (fr) 2009-03-27 2010-09-29 Deutsches Rheuma-Forschungszentrum Berlin Anticorps spécifiques à l'antigène syalilé pour le traitement ou prophylaxie des réactions immunitaires inflammatoires non désirables et leurs procédés de production
WO2010112556A1 (fr) 2009-03-31 2010-10-07 Charité - Universitätsmedizin Berlin Polypeptides et leur utilisation pour traiter une lésion neuronale d'origine traumatique ou dégénérative
EP2236516A1 (fr) 2009-03-31 2010-10-06 Charité-Universitätsmedizin Berlin (Charité) Polypeptides et utilisation associée pour le traitement d'une lésion neuronale traumatique ou dégénérative
WO2010136940A1 (fr) 2009-05-29 2010-12-02 Pfizer Limited Nouveaux agonistes du récepteur des glucocorticoïdes
EP2266563A1 (fr) 2009-06-11 2010-12-29 Charité-Universitätsmedizin Berlin (Charité) Utilisation d'antagonistes de récepteur opioïde pour le traitement aigu des états d'éveil paraphiliques
WO2011004276A1 (fr) 2009-07-06 2011-01-13 Pfizer Limited Inhibiteurs du virus de l’hépatite c
WO2011077313A1 (fr) 2009-12-22 2011-06-30 Pfizer Inc. Pipéridinecarboxamides en tant qu'inhibiteurs de mpges - 1
WO2011121558A1 (fr) 2010-04-02 2011-10-06 Phivco-1 Llc Traitement d'association comprenant un antagoniste du récepteur ccr5, un inhibiteur de la protéase du vih-1 et un accélérateur pharmacocinétique
WO2011138751A2 (fr) 2010-05-04 2011-11-10 Pfizer Inc. Dérivés hétérocycliques destinés au traitement de maladies
WO2011152720A1 (fr) 2010-05-31 2011-12-08 Umc St. Radboud Dérivés d'acide pantothénique et leur utilisation dans le traitement des infections microbiennes
WO2011152721A1 (fr) 2010-05-31 2011-12-08 Umc St. Radboud Dérivés de l'acide pantothénique et leur utilisation pour le traitement du paludisme
WO2011154871A1 (fr) 2010-06-10 2011-12-15 Pfizer Limited Inhibiteurs du virus de l'hépatite c
WO2012004743A1 (fr) 2010-07-09 2012-01-12 Pfizer Limited Benzènesulfonamides utiles en tant qu'inhibiteurs des canaux sodiques
WO2012004714A2 (fr) 2010-07-09 2012-01-12 Pfizer Limited Composés chimiques
WO2012004706A2 (fr) 2010-07-09 2012-01-12 Pfizer Limited Composés chimiques
WO2012007861A1 (fr) 2010-07-12 2012-01-19 Pfizer Limited Dérivés de n-sulfonylbenzamide utiles comme inhibiteurs du canal sodique voltage-dépendant
WO2012007877A2 (fr) 2010-07-12 2012-01-19 Pfizer Limited Composés chimiques
WO2012007883A1 (fr) 2010-07-12 2012-01-19 Pfizer Limited Composés chimiques
WO2012007869A2 (fr) 2010-07-12 2012-01-19 Pfizer Limited Composés chimiques
WO2012007868A2 (fr) 2010-07-12 2012-01-19 Pfizer Limited Composés chimiques
WO2012042421A1 (fr) 2010-09-29 2012-04-05 Pfizer Inc. Procédé de traitement de la croissance cellulaire anormale
WO2012066442A1 (fr) 2010-11-15 2012-05-24 Pfizer Limited Inhibiteurs de la réplication du vih
WO2012069175A1 (fr) 2010-11-25 2012-05-31 Almirall, S.A. Nouveaux dérivés de pyrazole possédant un comportement antagoniste de crth2
EP2457900A1 (fr) 2010-11-25 2012-05-30 Almirall, S.A. Nouveaux dérivés de pyrazole présentant un comportement antagoniste CRTH2
EP2463289A1 (fr) 2010-11-26 2012-06-13 Almirall, S.A. Dérivés imidazo[1,2-b]pyridazine en tant qu'inhibiteur JAK
WO2012069202A1 (fr) 2010-11-26 2012-05-31 Almirall,S.A. Dérivés d'imidazo[1,2-b]pyridazine et d'imidazo[4,5-b]pyridine en tant qu'inhibiteurs des jak
WO2012095781A1 (fr) 2011-01-13 2012-07-19 Pfizer Limited Dérivés d'indazole comme inhibiteurs des canaux sodiques
EP2489663A1 (fr) 2011-02-16 2012-08-22 Almirall, S.A. Composés en tant qu'inhibiteurs de la syk kinase
WO2012120398A1 (fr) 2011-03-04 2012-09-13 Pfizer Limited Dérivés de carboxamide substitués par aryle en tant que modulateurs de trpm8
WO2012137089A1 (fr) 2011-04-05 2012-10-11 Pfizer Limited Dérivés de pyrrolo-[2,3-d]pyrimidine en tant qu'inhibiteurs des kinases associées à la tropomyosine
EP2518070A1 (fr) 2011-04-29 2012-10-31 Almirall, S.A. Dérivés de pyrrolotriazinon en tant qu'inhibiteurs PI3K
US9011946B2 (en) 2011-04-29 2015-04-21 Intercontinental Great Brands Llc Encapsulated acid, method for the preparation thereof, and chewing gum comprising same
US9737082B2 (en) 2011-04-29 2017-08-22 Intercontinental Great Brands Llc Chewing gum composition comprising encapsulated acid
US9956211B2 (en) 2011-04-29 2018-05-01 Moberg Pharma Ab Pharmaceutical compositions comprising a local anaesthetic such as bupivacaine for local administration to the mouth or throat
US10493068B2 (en) 2011-04-29 2019-12-03 Moberg Pharma Ab Pharmaceutical compositions comprising a local anaesthetic such as bupivacaine for local administration to the mouth or throat
WO2012146667A1 (fr) 2011-04-29 2012-11-01 Almirall, S.A. Dérivés d'imidazopyridine en tant qu'inhibiteurs de pi3k
EP2518071A1 (fr) 2011-04-29 2012-10-31 Almirall, S.A. Dérivés d'imidazopyridine en tant qu'inhibiteurs PI3K
US9187463B2 (en) 2011-05-18 2015-11-17 Raqualia Pharma Inc. Polymorph form of 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid
KR20210104170A (ko) 2011-05-18 2021-08-24 라퀄리아 파마 인코포레이티드 4-｛[4-(｛[4-(2,2,2-트리플루오로에톡시)-1,2-벤즈이속사졸-3-일]옥시｝메틸)피페리딘-1-일]메틸｝-테트라히드로-2h-피란-4-카르복실산의 다형
WO2012157288A1 (fr) 2011-05-18 2012-11-22 Raqualia Pharma Inc. Forme polymorphe de l'acide 4-{[4-({[4-(2,2,2-trifluoroéthoxy)- 1,2-benzisoxazol-3-yl]oxy}méthyl)pipéridin-1-yl]méthyl}-tétrahydro-2h- pyran-4-carboxylique
WO2012160030A1 (fr) 2011-05-25 2012-11-29 Almirall, S.A. Dérivés de pyridin-2(1h)-one utiles en tant que médicaments pour le traitement de troubles myéloprolifératifs, du rejet de greffe, de maladies à médiation immunitaire et inflammatoires
EP2527344A1 (fr) 2011-05-25 2012-11-28 Almirall, S.A. Dérivés de pyridin-2(1h)-one utiles comme médicaments pour le traitement de maladies myeloproliferatives, de rejets de greffe, de maladies a médiation immune et de maladies inflammatoires
EP2526945A1 (fr) 2011-05-25 2012-11-28 Almirall, S.A. Nouveaux antagonistes de CRTH2
EP2548876A1 (fr) 2011-07-18 2013-01-23 Almirall, S.A. Nouveaux antagonistes de CRTH2
EP2548863A1 (fr) 2011-07-18 2013-01-23 Almirall, S.A. Nouveaux antagonistes de CRTH2
WO2013010881A1 (fr) 2011-07-18 2013-01-24 Almirall, S.A. Nouveaux antagonistes de crth2
WO2013010880A1 (fr) 2011-07-18 2013-01-24 Almirall, S.A. Nouveaux antagonistes de crth2
US8895544B2 (en) 2011-07-27 2014-11-25 Pfizer Limited Indazoles
WO2013014567A1 (fr) 2011-07-27 2013-01-31 Pfizer Limited Indazoles
US8575336B2 (en) 2011-07-27 2013-11-05 Pfizer Limited Indazoles
WO2013017461A1 (fr) 2011-08-01 2013-02-07 Almirall, S.A. Dérivés de pyridin-2(1h)-one en tant qu'inhibiteurs de jak
EP2554544A1 (fr) 2011-08-01 2013-02-06 Almirall, S.A. Dérivés de pyridin-2(1h)-one en tant qu'inhibiteurs de JAK
WO2013017989A1 (fr) 2011-08-02 2013-02-07 Pfizer Inc. Crizotinib pour l'utlisation dans le traitement de cancer
WO2013054185A1 (fr) 2011-10-13 2013-04-18 Pfizer, Inc. Dérivés de pyrimidine et de pyridine utiles en thérapie
WO2013057722A1 (fr) 2011-10-21 2013-04-25 Pfizer Limited Nouveau sel, et utilisation médicale
WO2013061205A2 (fr) 2011-10-26 2013-05-02 Pfizer Limited Composés chimiques
US9079878B2 (en) 2011-10-26 2015-07-14 Pfizer Limited (4-phenylimidazol-2-yl) ethylamine derivatives useful as sodium channel modulators
WO2013061297A1 (fr) 2011-10-28 2013-05-02 Pfizer Limited Dérivés de pyridazine utiles en thérapie
EP3243815A1 (fr) 2011-10-28 2017-11-15 Inhibitaxin Limited Dérivés de pyridazine utiles en thérapie
WO2013088315A1 (fr) 2011-12-15 2013-06-20 Pfizer Limited Dérivés de sulfonamide
WO2013093688A1 (fr) 2011-12-19 2013-06-27 Pfizer Limited Dérivés sulfonamides et leur utilisation en tant qu'inhibiteurs de vgsc
WO2013102826A1 (fr) 2012-01-04 2013-07-11 Pfizer Limited N-aminosulfonylbenzamides
US8927587B2 (en) 2012-02-03 2015-01-06 Pfizer Limited Chemical compounds
WO2013114250A1 (fr) 2012-02-03 2013-08-08 Pfizer Inc. Dérivés d'imidazopyridine et de benziimidazole en tant que modulateurs du canal sodium
WO2013132376A1 (fr) 2012-03-06 2013-09-12 Pfizer Inc. Dérivés macrocycliques pour le traitement de maladies prolifératives
US9533989B2 (en) 2012-09-18 2017-01-03 Ziarco Pharma Ltd. Substituted pyrimidine-5-carboxamides as spleen tyrosine kinase inhibitors
US10065964B2 (en) 2012-09-18 2018-09-04 Ziarco Pharma Ltd. Pyrimidine-5-carboxamides as spleen tyrosine kinase inhibitors
WO2014049488A1 (fr) 2012-09-28 2014-04-03 Pfizer Inc. Composés de benzamide et hétérobenzamide
WO2014053967A1 (fr) 2012-10-04 2014-04-10 Pfizer Limited Inhibiteurs de kinase associée à la tropomyosine pyrrolo[2,3-d]pyrimidine
WO2014053968A1 (fr) 2012-10-04 2014-04-10 Pfizer Limited Inhibiteurs de kinase associée à la tropomyosine pyrrolo[3,2-c]pyridine
WO2014053965A1 (fr) 2012-10-04 2014-04-10 Pfizer Limited Inhibiteurs de kinases apparentés à la tropomyosine
WO2014060431A1 (fr) 2012-10-16 2014-04-24 Almirall, S.A. Dérivés de pyrrolotriazinone en tant qu'inhibiteurs des pi3k
US9527843B2 (en) 2012-11-08 2016-12-27 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
WO2014072881A1 (fr) 2012-11-08 2014-05-15 Pfizer Inc. Composés hétéroaromatiques et leur utilisation comme ligands de la dopamine d1
WO2014072882A1 (fr) 2012-11-08 2014-05-15 Pfizer Inc. Composés hétéroaromatiques utilisés comme ligands de la dopamine d1
US8822494B2 (en) 2012-11-08 2014-09-02 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
EP3323821A1 (fr) 2012-11-08 2018-05-23 Pfizer Inc Composes heteroaromatiques et leur utilisation comme ligands du recepteur d1 de la dopamine
US9133190B2 (en) 2012-11-08 2015-09-15 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
US9617275B2 (en) 2012-11-08 2017-04-11 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
KR20150085515A (ko) 2012-11-21 2015-07-23 라퀄리아 파마 인코포레이티드 다형체
US10179779B2 (en) 2012-11-21 2019-01-15 Raqualia Pharma Inc. Polymorph forms
WO2014087298A1 (fr) 2012-12-03 2014-06-12 Pfizer Inc. Nouveaux modulateurs androgéniques sélectifs
US9328104B2 (en) 2012-12-03 2016-05-03 Pfizer Inc. Selective androgen receptor modulators
WO2014091368A1 (fr) 2012-12-14 2014-06-19 Pfizer Limited Dérivés d'imidazopyridazine en tant que modulateurs d'un récepteur gabaa
WO2014097041A1 (fr) 2012-12-21 2014-06-26 Pfizer Inc. Lactames fusionnés à un aryle et hétéroaryle
EP3339303A1 (fr) 2012-12-21 2018-06-27 Pfizer Inc Lactames fusionnés à un aryle et hétéroaryle
WO2014124757A1 (fr) 2013-02-15 2014-08-21 Almirall, S.A. Dérivés de pyrrolotriazinone utilisés en tant qu'inhibiteurs de pi3k
WO2014128588A1 (fr) 2013-02-21 2014-08-28 Pfizer Inc. Formes solides d'un inhibiteur sélectif de cdk4/6
EP3431475A1 (fr) 2013-02-21 2019-01-23 Pfizer Inc Formes solides d'un inhibiteur sélectif de cdk4/6
EP2792360A1 (fr) 2013-04-18 2014-10-22 IP Gesellschaft für Management mbH (1aR,12bS)-8-cyclohexyl-11-fluoro-N-((1-methylcyclopropyl)sulfonyl)-1a-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-1,1a,2,2b-tetrahydrocyclopropa[d]indolo[2,1-a][2]benzazepine-5-carboxamide pour utilisation dans le traitement de HCV
WO2014170792A1 (fr) 2013-04-19 2014-10-23 Pfizer Limited Dérivés sulfonamides utilisés comme inhibiteurs de l'urat-1
WO2014170793A1 (fr) 2013-04-19 2014-10-23 Pfizer Limited Sulfonamides pour le traitement de la goutte
WO2014181213A1 (fr) 2013-05-10 2014-11-13 Pfizer Inc. Forme cristalline de (sa)-(-)-3-(3-bromo-4-((2,4-difluorobenzyl)oxy)-6-methyl-2-oxopyridin-1 (2h)-yl)-n,4-dimethylbenzamide
WO2014186742A2 (fr) 2013-05-17 2014-11-20 Acupac Packaging, Inc. Composition d'hydrogel anhydre
US10696658B2 (en) 2013-06-27 2020-06-30 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
US9527831B2 (en) 2013-06-27 2016-12-27 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
US9822097B2 (en) 2013-06-27 2017-11-21 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
WO2014207601A1 (fr) 2013-06-27 2014-12-31 Pfizer Inc. Composés hétéro-aromatiques et leur utilisation en tant que ligands d1 de la dopamine
US10421744B2 (en) 2013-06-27 2019-09-24 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
EP3421462A1 (fr) 2013-06-27 2019-01-02 Pfizer Inc Composés hétéro-aromatiques et leur utilisation en tant que ligands d1 de la dopamine
US10093655B2 (en) 2013-06-27 2018-10-09 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
US11964961B2 (en) 2013-06-27 2024-04-23 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
US11014909B2 (en) 2013-06-27 2021-05-25 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
US9107923B2 (en) 2013-06-27 2015-08-18 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
US9139561B2 (en) 2013-06-27 2015-09-22 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
WO2015050989A2 (fr) 2013-10-01 2015-04-09 Cs Therapeutics Inc. Composés macrocycliques destinés au traitement de maladies prolifératives
WO2015092610A1 (fr) 2013-12-20 2015-06-25 Pfizer Limited Inhibiteurs de kinase apparentés à la n-acylpipéridine éther tropomyosine
WO2015092614A1 (fr) 2013-12-20 2015-06-25 Pfizer Inc. Altérations d'activation de notch dans le cancer du sein
WO2015159175A1 (fr) 2014-04-15 2015-10-22 Pfizer Inc. Inhibiteurs de kinases apparentées à la tropomyosine contenant à la fois un 1h-pyrazole et un fragment pyrimidine
US9850232B2 (en) 2014-04-25 2017-12-26 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
US9688698B2 (en) 2014-04-25 2017-06-27 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
WO2015162516A1 (fr) 2014-04-25 2015-10-29 Pfizer Inc. Composés hétéroaromatiques et leur utilisation comme ligands de la dopamine d1
US9540352B2 (en) 2014-04-25 2017-01-10 Pfizer Inc. Substituted 1,7-naphthyridines as dopamine D1 ligands
WO2015162515A1 (fr) 2014-04-25 2015-10-29 Pfizer Inc. Composés hétéroaromatiques et leur utilisation comme ligands de la dopamine d1
WO2015162518A1 (fr) 2014-04-25 2015-10-29 Pfizer Inc. Composes hetero-aromatiques et leur utilisation comme ligands d1 de la dopamine
US9745317B2 (en) 2014-04-28 2017-08-29 Pfizer Inc. Heterocyclic compounds and their use as dopamine D1 ligands
US9856263B2 (en) 2014-04-28 2018-01-02 Pfizer Inc. Heteroaromatic compounds and their use as dopamine D1 ligands
WO2015166366A1 (fr) 2014-04-28 2015-11-05 Pfizer Inc. Composés hétérocycliques et leur utilisation comme ligands des récepteurs d1 de la dopamine
WO2015166370A1 (fr) 2014-04-28 2015-11-05 Pfizer Inc. Composés hétéroaromatiques et leur utilisation en tant que ligands de la dopamine d1
WO2015170218A1 (fr) 2014-05-07 2015-11-12 Pfizer Inc. Inhibiteurs de kinases apparentées à la tropomyosine
US9518052B2 (en) 2014-05-14 2016-12-13 Pfizer Inc. Pyrazolopyridines and pyrazolopyrimidines
WO2015173683A1 (fr) 2014-05-14 2015-11-19 Pfizer Inc. Pyrazolopyridines et pyrazolopyrimidines
US10022376B2 (en) 2014-05-14 2018-07-17 Pfizer Inc. Pyrazolopyridines and pyrazolopyrimidines
US9920043B2 (en) 2014-05-15 2018-03-20 Pfizer Inc. Crystalline form of 6-[(4R)-4-methyl-1,2-dioxido-1,2,6-thiadiazinan-2-yl]iosoquinoline-1-carbonitrile
WO2015173684A1 (fr) 2014-05-15 2015-11-19 Pfizer Inc. Forme cristalline du 6-[(4r)-4-méthyl -1,2-dioxydo-1,2,6-thiadiazinan -2-yle]isoquinoline-1-carbonitrile
US9988370B2 (en) 2014-05-20 2018-06-05 Raqualia Pharma Inc. Benzisoxazole derivative salt
WO2015181797A1 (fr) 2014-05-30 2015-12-03 Pfizer Inc. Benzènesulfonamides utiles en tant qu'inhibiteurs des canaux sodiques
WO2015181676A1 (fr) 2014-05-30 2015-12-03 Pfizer Inc. Dérivés carbonitriles en tant que modulateurs sélectifs du récepteur des androgènes
US10328082B2 (en) 2014-05-30 2019-06-25 Pfizer Inc. Methods of use and combinations
WO2015189744A1 (fr) 2014-06-12 2015-12-17 Pfizer Limited Dérivés d'imidazopyridazine utilisés comme modulateurs de l'activité des récepteurs gabaa.
WO2015193768A1 (fr) 2014-06-17 2015-12-23 Pfizer Inc. Lactames à fusion aryle à utiliser en tant que modulateurs ezh2
WO2015193765A1 (fr) 2014-06-17 2015-12-23 Pfizer Inc. Composés dihydroisoquinolinone substitués
EP3521285A1 (fr) 2014-06-17 2019-08-07 Pfizer Inc Composés dihydroisoquinolinone substitués
WO2016009296A1 (fr) 2014-07-16 2016-01-21 Pfizer Inc. Inhibiteurs de kinase liés à la n-acylpipéridine éther tropomyosine
WO2016009303A1 (fr) 2014-07-17 2016-01-21 Pfizer Inc. Associations de produits pharmaceutiques comprenant de la gabapentine ou de la prégabaline avec des inhibiteurs de nav1.7
WO2016009297A1 (fr) 2014-07-18 2016-01-21 Pfizer Inc. Dérivés de la pyridine en tant que modulateurs allostériques positifs du récepteur m1 muscarinique
WO2016020784A1 (fr) 2014-08-05 2016-02-11 Pfizer Inc. Inhibiteurs de kinases apparentées à la n-acylpyrrolidine éther tropomyosine
WO2016034971A1 (fr) 2014-09-04 2016-03-10 Pfizer Limited Dérivés sulfonamides utilisés en tant qu'inhibiteurs d'urat1
WO2016044433A2 (fr) 2014-09-16 2016-03-24 Biopharma Works Dérivés de la metformine
US11229652B2 (en) 2014-09-29 2022-01-25 The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin Treatments for autoimmune disease
US10793572B2 (en) 2014-09-29 2020-10-06 The Provost Fellows Foundation Scholars And The Other Members Of Board Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Substituted pyrimidine derivatives useful in the treatment of autoimmune diseases
WO2016067143A1 (fr) 2014-10-28 2016-05-06 Pfizer Inc. Composés n- (2-alkylèneimino-3-phénylpropyl)acétamide et leur utilisation contre la douleur et le prurit par inhibition des canaux trpa1
WO2016072854A2 (fr) 2014-11-06 2016-05-12 Radboud Universitair Medisch Centrum Analogues de pantothénamide
WO2016097918A1 (fr) 2014-12-18 2016-06-23 Pfizer Inc. Dérivés de pyrimidine et de triazine, et leur utilisation comme inhibiteurs d'axl
US9593097B2 (en) 2014-12-18 2017-03-14 Pfizer Inc. Axl inhibitors
EP3556376A1 (fr) 2015-01-22 2019-10-23 Phytoplant Research S.L. Procédés de purification de cannabinoïdes, compositions et kits correspondants
WO2016116628A1 (fr) 2015-01-22 2016-07-28 Phytoplant Research S.L. Procédés de purification de cannabinoïdes, compositions de cannabinoïdes et trousses associées
US10428104B2 (en) 2015-02-24 2019-10-01 Pfizer Inc. Substituted nucleoside derivatives useful as anticancer agents
US10624972B2 (en) 2015-03-13 2020-04-21 Endocyte, Inc. Conjugates for treating diseases
WO2016170009A1 (fr) 2015-04-21 2016-10-27 Almirall, S.A. Dérivés hétérocycliques amino-substitués utilisés comme inhibiteurs des canaux sodiques
US10723711B2 (en) 2015-07-31 2020-07-28 Pfizer Inc. 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate derivatives and 1,1,1-trifluoro-4-hydroxybutan-2-yl carbamate derivatives as MAGL inhibitors
US10428034B2 (en) 2015-07-31 2019-10-01 Pfizer Inc. 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate derivatives and 1,1,1-trifluoro-4-hydroxybutan-2-yl carbamate derivatives as MAGL inhibitors
WO2017021805A1 (fr) 2015-07-31 2017-02-09 Pfizer Inc. Dérivés de carbamate de 1,1,1-trifluoro-3-hydroxypropan-2-yle et dérivés de carbamate de 1,1,1-trifluoro-4-hydroxybutan-2-yle comme inhibiteurs de magl
US9845301B2 (en) 2015-07-31 2017-12-19 Pfizer Inc. 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate derivatives and 1,1,1-trifluoro-4-hydroxybutan-2-yl carbamate derivatives as MAGL inhibitors
WO2017060488A1 (fr) 2015-10-09 2017-04-13 Almirall, S.A. Nouveaux antagonistes de trpa1
WO2017064068A1 (fr) 2015-10-14 2017-04-20 Almirall, S.A. Nouveaux antagonistes de trpa1
WO2017098367A1 (fr) 2015-12-10 2017-06-15 Pfizer Limited Dérivés 4-(biphényl-3-yl)-1h-pyrazolo[3,4-c]pyridazine de formule (i) utilisés comme modulateurs de récepteur gaba pour le traitement de l'épilepsie et de la douleur
US11553723B2 (en) 2015-12-11 2023-01-17 Wm. Wrigley Jr. Company Color indicating formulations
WO2017100784A1 (fr) * 2015-12-11 2017-06-15 Wm. Wrigley Jr. Company Formulations à indicateur de couleur
WO2017120429A1 (fr) 2016-01-07 2017-07-13 CS Pharmasciences, Inc. Inhibiteurs sélectifs de mutants cliniquement importants de la tyrosine kinase de l'egfr
WO2017119732A1 (fr) 2016-01-08 2017-07-13 Samsung Electronics Co., Ltd. Dispositif électronique, et son procédé de fonctionnement
WO2017122116A1 (fr) 2016-01-15 2017-07-20 Pfizer Inc. Ligands 6,7,8,9-tétrahydro-5h-pyrido[2,3-d]azépine du récepteur d3 de la dopamine
WO2017156341A1 (fr) 2016-03-09 2017-09-14 Beijing Percans Oncology Co. Ltd. Cultures en suspension de cellules tumorales et procédés associés
US10220037B2 (en) 2016-06-06 2019-03-05 Pfizer Inc. Substituted carbonucleoside derivatives useful as anticancer agents
WO2017212385A1 (fr) 2016-06-06 2017-12-14 Pfizer Inc. Dérivés de carbonucléosides substitués utiles en tant qu'agents anticancéreux
US10709709B2 (en) 2016-06-06 2020-07-14 Pfizer Inc. Substituted carbonucleoside derivatives useful as anticancer agents
WO2018033815A1 (fr) 2016-08-15 2018-02-22 Pfizer Inc. Inhibiteurs de pyridopyrimidinone cdk2/4/6
WO2018096510A1 (fr) 2016-11-28 2018-05-31 Pfizer Inc. Ligands opioïdes kappa hétéroarylphénoxy benzamide
EP4252856A2 (fr) 2016-12-20 2023-10-04 Oligomerix, Inc. Nouvelles quinazolinones inhibant la formation d'oligomères tau et leur procédé d'utilisation
US10626125B2 (en) 2017-01-20 2020-04-21 Pfizer Inc. 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate derivatives as MAGL inhibitors
US10329308B2 (en) 2017-01-20 2019-06-25 Pfizer Inc. 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate derivatives as MAGL inhibitors
WO2018134695A1 (fr) 2017-01-20 2018-07-26 Pfizer Inc. Dérivés de 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate utilisés comme inhibiteurs de la magl
WO2018134698A1 (fr) 2017-01-23 2018-07-26 Pfizer Inc. Composés spiro hétérocycliques utilisés en tant qu'inhibiteurs de magl
US10858373B2 (en) 2017-01-23 2020-12-08 Pfizer Inc. Heterocyclic spiro compounds as MAGL inhibitors
WO2018138591A1 (fr) 2017-01-24 2018-08-02 Pfizer Inc. Dérivés de calichéamicine et conjugués anticorps-médicaments de ceux-ci
EP4074309A1 (fr) 2017-05-30 2022-10-19 Enorama Pharma AB Compositions de gomme à mâcher contenant de la nicotine
WO2018219650A1 (fr) 2017-05-30 2018-12-06 Enorama Pharma Ab Compositions de gomme à mâcher contenant de la nicotine
US11571423B2 (en) 2017-06-22 2023-02-07 Curadev Pharma Limited Small molecule modulators of human sting
US11773132B2 (en) 2017-08-30 2023-10-03 Beijing Xuanyi Pharmasciences Co., Ltd. Cyclic di-nucleotides as stimulator of interferon genes modulators
WO2019051469A1 (fr) 2017-09-11 2019-03-14 Krouzon Pharmaceuticals, Inc. Inhibiteurs allostériques octahydrocyclopenta[c]pyrrole de shp2
US10435389B2 (en) 2017-09-11 2019-10-08 Krouzon Pharmaccuticals, Inc. Octahydrocyclopenta[c]pyrrole allosteric inhibitors of SHP2
WO2019097369A1 (fr) 2017-11-14 2019-05-23 Pfizer Inc. Polythérapies faisant appel à un inhibiteur de ezh2
WO2019145552A1 (fr) 2018-01-29 2019-08-01 Phytoplant Research S.L Procédés de purification de cannabinoïdes par chromatographie liquide : liquide
US10662204B2 (en) 2018-02-01 2020-05-26 Pfizer Inc. Substituted quinazoline and pyridopyrimidine derivatives useful as anticancer agents
WO2019150305A1 (fr) 2018-02-01 2019-08-08 Pfizer Inc. Dérivés de quinazoline et de pyridopyrimidine substitués utiles en tant qu'agents anticancéreux
WO2019155399A1 (fr) 2018-02-09 2019-08-15 Pfizer Inc. Dérivés de tétrahydroquinazoline utiles en tant qu'agents anticancéreux
US10590115B2 (en) 2018-02-09 2020-03-17 Pfizer Inc. Tetrahydroquinazoline derivatives useful as anticancer agents
WO2019166928A1 (fr) 2018-02-27 2019-09-06 Pfizer Inc. Association d'un inhibiteur de kinases dépendantes des cyclines et d'un inhibiteur de bromodomaines bet
WO2019207463A1 (fr) 2018-04-26 2019-10-31 Pfizer Inc. Dérivés de 2-amino-pyridine ou de 2-amino-pyrimidine utilisés en tant qu'inhibiteurs de kinases dépendantes des cyclines
WO2019243823A1 (fr) 2018-06-21 2019-12-26 Curadev Pharma Limited Modulateurs azahétérocycliques à petites molécules de sting humain
WO2020016710A1 (fr) 2018-07-19 2020-01-23 Pfizer Inc. Composés spiro hétérocycliques utilisés en tant qu'inhibiteurs de magl
WO2020100027A1 (fr) 2018-11-15 2020-05-22 Pfizer Inc. Dérivés de 2,3-dihydro-1h-pyrrolo[3,4-c]pyridin-1-one servant d'inhibiteurs de hpk1 pour le traitement du cancer
US11572336B2 (en) 2018-12-31 2023-02-07 Mmv Medicines For Malaria Venture Pantothenamide analogues
WO2020141155A1 (fr) 2018-12-31 2020-07-09 Mmv Medicines For Malaria Venture Analogues de pantothénamide
EP3674288A1 (fr) 2018-12-31 2020-07-01 MMV Medicines for Malaria Venture Analogues de pantothénamide
US11834391B2 (en) 2018-12-31 2023-12-05 Mmv Medicines For Malaria Venture Pantothenamide analogues
WO2020152557A1 (fr) 2019-01-23 2020-07-30 Pfizer Inc. Forme polymorphe d'un sel d'hydrate de monophosphate d'un dérivé de tétrahydroisoquinoline connu
WO2020157652A2 (fr) 2019-01-31 2020-08-06 Pfizer Inc. Inhibiteurs de cdk2
WO2020157709A1 (fr) 2019-02-01 2020-08-06 Pfizer Inc. Association d'un inhibiteur de cdk et d'un inhibiteur de pim
WO2021009676A1 (fr) 2019-07-17 2021-01-21 Pfizer Inc. Dérivés d'imidazo [4,5-c] pyridine en tant qu'agonistes du récepteur de type toll
WO2021014415A2 (fr) 2019-07-25 2021-01-28 Curadev Pharma Pvt. Ltd. Inhibiteurs à petites molécules de l'acétyl-coenzyme a synthétase à chaîne courte 2 (acss2)
WO2021161230A1 (fr) 2020-02-12 2021-08-19 Curadev Pharma Pvt. Ltd. Antagonistes de sting à petites molécules
WO2021176349A1 (fr) 2020-03-05 2021-09-10 Pfizer Inc. Combinaison d'un inhibiteur de kinase du lymphome anaplasique et d'un inhibiteur de kinase dépendant de la cycline
WO2021205363A1 (fr) 2020-04-08 2021-10-14 Pfizer Inc. Co-traitement avec des inhibiteurs de cdk4/6 et de cdk2 pour supprimer l'adaptation tumorale à des inhibiteurs de cdk2
WO2021220185A1 (fr) 2020-05-01 2021-11-04 Pfizer Inc. Composés d'azalactame utilisé en tant qu'inhibiteurs de hpk1
WO2021224818A1 (fr) 2020-05-08 2021-11-11 Pfizer Inc. Composés d'isoindolone en tant qu'inhibiteurs de hpk1
WO2022003575A1 (fr) 2020-06-30 2022-01-06 Array Biopharma Inc. Inhibiteurs de mutation her2
US11324727B2 (en) 2020-07-15 2022-05-10 Schabar Research Associates, Llc Unit oral dose compositions composed of naproxen sodium and famotidine for the treatment of acute pain and the reduction of the severity of heartburn and/or the risk of heartburn
US11331307B2 (en) 2020-07-15 2022-05-17 Schabar Research Associates, Llc Unit oral dose compositions composed of ibuprofen and famotidine for the treatment of acute pain and the reduction of the severity and/or risk of heartburn
WO2022013692A1 (fr) 2020-07-15 2022-01-20 Pfizer Inc. Polymorphes de (1s,2s,3s,5r)-3-((6-(difluorométhyl)-3-((6-(difluorométhyl)-5-fluoro-1,2,3,4-tétrahydroisoquinolin-8-yl)oxy)-5-(4-méthyl-7h-pyrrolo[2,3-d]pyrimidin-7-yl) cyclopentane-1,2-diol monochlorhydrate
WO2022013691A1 (fr) 2020-07-15 2022-01-20 Pfizer Inc. Polymorphe de (1s,2s,3s,5r)-3-((6-(difluorométhyl)-5-flu­oro-1,2,3,4-tétrahydroisoquinolin-8-yl)oxy)-5-(4-méthyl-7h-pyrrolo[2,3-d]­pyrimidin-7-yl)cyclopentane-1,2-diol
WO2022018596A1 (fr) 2020-07-20 2022-01-27 Pfizer Inc. Polythérapie
WO2022018667A1 (fr) 2020-07-24 2022-01-27 Pfizer Inc. Polythérapies utilisant des inhibiteurs de cdk2 et de cdc25a
WO2022023433A1 (fr) 2020-07-29 2022-02-03 The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin Composés
WO2022023438A1 (fr) 2020-07-29 2022-02-03 The Provost, Fellows, Foundation Scholars, And The Other Members Of Board, Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth, Near Dublin Composés
WO2022034504A1 (fr) 2020-08-13 2022-02-17 Pfizer Inc. Polythérapie
WO2022058871A1 (fr) 2020-09-15 2022-03-24 Pfizer Inc. Formes solides d'un inhibiteur de cdk4
WO2022137174A1 (fr) 2020-12-22 2022-06-30 Pfizer Inc. Formes solides d'un inhibiteur de eif4e
WO2022137106A1 (fr) 2020-12-24 2022-06-30 Pfizer Inc. Formes solides d'un inhibiteur de cdk2
WO2022195462A1 (fr) 2021-03-18 2022-09-22 Pfizer Inc. Modulateurs de sting (stimulateur des gènes de l'interféron)
WO2022200982A1 (fr) 2021-03-24 2022-09-29 Pfizer Inc. Combinaison de talazoparib et d'un anti-androgène pour le traitement du cancer de la prostate métastatique sensible à la castration et muté par le gène ddr
WO2022207673A1 (fr) 2021-03-31 2022-10-06 Sevenless Therapeutics Limited Inhibiteurs de sos1 et inhibiteurs de ras destinés à être utilisés dans le traitement de la douleur
GB202104609D0 (en) 2021-03-31 2021-05-12 Sevenless Therapeutics Ltd New Treatments for Pain
WO2022214869A2 (fr) 2021-04-07 2022-10-13 Lifearc Inhibiteurs ulk1/2 et leur utilisation
WO2022229846A1 (fr) 2021-04-29 2022-11-03 Pfizer Inc. Traitement du cancer à l'aide d'un inhibiteur du récepteur du facteur de croissance transformant bêta de type 1
WO2022269531A1 (fr) 2021-06-26 2022-12-29 Array Biopharma Inc. Inhibiteurs de mutation her2
WO2023002362A1 (fr) 2021-07-22 2023-01-26 Pfizer Inc. Traitement d'une malignité hématologique
WO2023017452A1 (fr) 2021-08-11 2023-02-16 Curadev Pharma Pvt. Ltd. Dérivés d'urée à petites molécules en tant qu'antagonistes de sting
WO2023017451A1 (fr) 2021-08-11 2023-02-16 Curadev Pharma Pvt. Ltd. Antagonistes de sting à petites molécules
WO2023084459A1 (fr) 2021-11-15 2023-05-19 Pfizer Inc. Méthodes de traitement du sars-cov-2
WO2023099072A1 (fr) 2021-12-01 2023-06-08 Fundación Del Sector Público Estatal Centro Nacional De Investigaciones Oncológicas Carlos III (F.S.P. CNIO) Composés
WO2023100134A1 (fr) 2021-12-02 2023-06-08 Pfizer Inc. Méthodes et schémas posologiques comprenant un inhibiteur de cdk2 et un inhibiteur de cdk4 pour le traitement du cancer
WO2024023727A1 (fr) 2022-07-29 2024-02-01 Pfizer Inc. Nouveaux inhibiteurs de l'acc
WO2024033513A1 (fr) 2022-08-11 2024-02-15 Diaccurate Composés pour le traitement du cancer
WO2024074827A1 (fr) 2022-10-05 2024-04-11 Sevenless Therapeutics Limited Nouveaux traitements de la douleur

Also Published As

Publication number Publication date
WO2000035296A1 (fr) 2000-06-22

Similar Documents

Publication Publication Date Title
US6949264B1 (en) Nutraceuticals or nutritional supplements and method of making
US6627234B1 (en) Method of producing active agent coated chewing gum products
US7163705B2 (en) Coated chewing gum product and method of making
WO2000035298A1 (fr) Chewing-gum contenant des agents medicamenteux actifs
US6586023B1 (en) Process for controlling release of active agents from a chewing gum coating and product thereof
US6350480B1 (en) Chewing gum product including a hydrophilic gum base and method of producing
US6592850B2 (en) Sildenafil citrate chewing gum formulations and methods of using the same
EP2083633A1 (fr) Véhicules d'administration orale contenant un médicament traditionnel chinois ou un extrait de celui-ci
WO2002013781A1 (fr) Procede de preparation d'une gomme a macher ayant un gout agreable pour le consommateur
US6645535B2 (en) Method of making coated chewing gum products containing various antacids
EP1416806A1 (fr) Procede de fabrication de produits de gomme a macher enrobes comprenant un edulcorant de haute intensite
AU1937700A (en) Controlling release of active agents from a chewing gum coating
US6579545B2 (en) Coated chewing gum products containing an antigas agent
US20030180414A1 (en) Method of controlling release of bitterness inhibitors in chewing gum and gum produced thereby
CA2394290C (fr) Chewing gum a liberation de principes actifs lipophiles
US20100104518A1 (en) Chewing gum, confection, and other oral delivery vehicles containing a traditional chinese medicine or extract thereof
AU765999B2 (en) Improved release of medicament active agents from a chewing gum coating
EP1409020A1 (fr) Produits de gommes a macher enrobes de matieres antiacides a viscosite elevee
AU2004200574B2 (en) Controlling Release of Active Agents from a Chewing Gum Coating

Legal Events

Date Code Title Description
ENP Entry into the national phase

Ref country code: US

Ref document number: 1999 308972

Date of ref document: 19990527

Kind code of ref document: A

Format of ref document f/p: F

AK Designated states

Kind code of ref document: A1

Designated state(s): US US US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 1999966283

Country of ref document: EP

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWP Wipo information: published in national office

Ref document number: 1999966283

Country of ref document: EP