WO2008045579A1 - Véhicules d'administration orale contenant un médicament traditionnel chinois ou un extrait de celui-ci - Google Patents

Véhicules d'administration orale contenant un médicament traditionnel chinois ou un extrait de celui-ci Download PDF

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Publication number
WO2008045579A1
WO2008045579A1 PCT/US2007/060583 US2007060583W WO2008045579A1 WO 2008045579 A1 WO2008045579 A1 WO 2008045579A1 US 2007060583 W US2007060583 W US 2007060583W WO 2008045579 A1 WO2008045579 A1 WO 2008045579A1
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WIPO (PCT)
Prior art keywords
chinese medicine
traditional chinese
active agent
coating
medicine active
Prior art date
Application number
PCT/US2007/060583
Other languages
English (en)
Inventor
Jianwei J. Cai
Minmin Tian
Michael J. Greenburg
Scott W. Marske
Biao Che
Albert H. Chapdelaine
Zheng Xia Han
Wen Xiong Huang
Original Assignee
Wm. Wrigley Jr. Company
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Publication date
Application filed by Wm. Wrigley Jr. Company filed Critical Wm. Wrigley Jr. Company
Priority to US12/444,680 priority Critical patent/US20100104518A1/en
Priority to EP07710146A priority patent/EP2083633A4/fr
Publication of WO2008045579A1 publication Critical patent/WO2008045579A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • 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
    • A23G1/00—Cocoa; Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/30—Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/32—Cocoa products, e.g. chocolate; Substitutes therefor 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
    • A23G1/00—Cocoa; Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/30—Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/32—Cocoa products, e.g. chocolate; Substitutes therefor characterised by the composition containing organic or inorganic compounds
    • A23G1/42—Cocoa products, e.g. chocolate; Substitutes therefor characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • 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
    • A23G1/00—Cocoa; Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/30—Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/32—Cocoa products, e.g. chocolate; Substitutes therefor characterised by the composition containing organic or inorganic compounds
    • A23G1/48—Cocoa products, e.g. chocolate; Substitutes therefor 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
    • A23G1/00—Cocoa; Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/30—Cocoa products, e.g. chocolate; Substitutes therefor
    • A23G1/50—Cocoa products, e.g. chocolate; Substitutes therefor characterised by shape, structure or physical form, e.g. products with an inedible support
    • A23G1/54—Composite products, e.g. layered laminated, coated, filled
    • 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
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof 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
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A23G3/364—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • 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
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A23G3/48—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof 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
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/50—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by shape, structure or physical form, e.g. products with supported structure
    • A23G3/54—Composite products, e.g. layered, coated, filled
    • 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
    • A23G4/06—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
    • A23G4/12—Chewing gum characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • 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
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P20/00—Coating of foodstuffs; Coatings therefor; Making laminated, multi-layered, stuffed or hollow foodstuffs
    • A23P20/10—Coating with edible coatings, e.g. with oils or fats
    • A23P20/12—Apparatus or processes for applying powders or particles to foodstuffs, e.g. for breading; Such apparatus combined with means for pre-moistening or battering
    • 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
    • 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

Definitions

  • the present invention relates to methods for producing chewing gum
  • the invention relates to producing chewing gum, other confections, or other oral delivery vehicles such as sprays, foams, pearls, drops, and films, containing an effective amount of traditional Chinese medicine ("TMC") or a hydrophilic or hydrophobic solvent or supercritical fluid extract of traditional Chinese medicines.
  • TMC traditional Chinese medicine
  • 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.
  • the active medicament is formulated in a confection such as a compressed mint, chewy candy, or lozenge or other oral delivery vehicle to maximize effectiveness and good taste.
  • 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.
  • 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.
  • 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 drags, 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. [017] There is therefore a need for an improved method of delivering drugs and agents to an individual.
  • the present invention provides improved methods for delivering a traditional Chinese medicine or its extract 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 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 active 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 present invention also provides active delivery comprising the steps of providing a confection that includes the active n the confection composition, sucking or chewing the confection to cause the medicament to be released into the buccal cavity of the consumer.
  • active delivery comprising the steps of providing a spray, foam, pearls, or films that includes the active medicament in the formulation of these products and spraying, chewing or sucking the product releases the active into the oral cavity of the consumer. Absorption can take place sublingually, bucally or through the gastointestinal system.
  • the active medicament used in the present invention may be any agent that is traditionally used as a health aid, or medicament and lends itself to being administered through the oral cavity.
  • traditional Chinese medicine active agent as used herein and in the claims includes traditional Chinese medicines, or hydrophilic or hydrophobic solvent extracts thereof.
  • Such active agents may be:
  • 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 improved stability of active medicaments allowing a known dose to be delivered orally, and increase absorption and bioavailability as compared to medicaments that are formulated in foods and beverages and are designed to be absorbed in the GI tract.
  • 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 medicament actives 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.
  • an advantage of the present invention is to provide an improved delivery method for traditional Chinese medicine or there extracts.
  • 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, stcviosidc and dihydrochalconcs.
  • 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 preparation of confectionery formulations is historically well known and has changed little through the years. Confectionery items have been classified as either "hard” confectionery or "soft” confectionery.
  • the traditional Chinese medicines of the present invention may be incorporated into confectionery compositions by admixing the inventive composition into conventional hard and soft confections.
  • confectionery material means a product containing a bulking agent selected from a wide variety of materials such as sugar, corn syrup, and in the case of sugarless bulking agents, sugar alcohols such as sorbitol, xylitol and mannitol and mixtures thereof.
  • Confectionery material may include such exemplary substances as lozenges, tablets, toffee, nougat, suspensions, chewy candy, chewing gum and the like.
  • the bulking agent is present in a quantity sufficient to bring the total amount of composition to 100%. In general, the bulking agent will be present in amounts up to about 99.98%, preferably in amounts up to about 99.9%, and more preferably in amounts up to about 99%, by weight of the traditional Chinese medicines composition.
  • Lozenges are flavored dosage forms intended to be sucked and held in the mouth. Lozenges may be in the form of various shapes such as flat, circular, octagonal and biconvex forms.
  • the lozenge bases are generally in two forms: hard boiled candy lozenges and compressed tablet lozenges.
  • Hard boiled candy lozenges may be processed and formulated by conventional means. In general, a hard boiled candy lozenge has a base composed of a mixture of sugar and other carbohydrate bulking agents kept in an amorphous or glassy condition. This amorphous or glassy form is considered a solid syrup of sugars generally having from about 0.5% to about 1.5% moisture.
  • Such materials normally contain up to about 92% corn syrup, up to about 55% sugar and from about 0.1% to about 5% water, by weight of the final composition.
  • the syrup component is generally prepared from corn syrups high in fructose, but may include other materials. Further ingredients such as flavoring agents, sweetening agents, acidulants, coloring agents and the like may also be added.
  • Boiled candy lozenges may also be prepared from non-fermentable sugars such as sorbitol, mannitol, and hydrogenated corn syrup. Typical hydrogenated corn syrups are Lycasin, a commercially available product manufactured by Roquette Corporation, and Hystar, a commercially available product manufactured by Lonza, Inc.
  • the candy lozenges may contain up to about 95% sorbitol, a mixture of sorbitol and mannitol in a ratio from about 9.5:0.5 up to about 7.5:2.5, and hydrogenated corn syrup up to about 55%, by weight of the solid syrup component.
  • Boiled candy lozenges may be routinely prepared by conventional methods such as those involving fire cookers, vacuum cookers, and scraped- surface cookers also referred to as high speed atmospheric cookers.
  • Fire cookers involve the traditional method of making a boiled candy lozenge base. In this method, the desired quantity of carbohydrate bulking agent is dissolved in water by heating the agent in a kettle until the bulking agent dissolves. Additional bulking agent may then be added and cooking continued until a final temperature of 145 0 C. to 156°C. is achieved. The batch is then cooled and worked as a plastic-like mass to incorporate additives such as flavors, colorants and the like.
  • a high-speed atmospheric cooker uses a heat-exchanger surface which involves spreading a film of candy on a heat exchange surface, the candy is heated to 165°C. to 170°C. in a few minutes. The candy is then rapidly cooled to 100 0 C. to 120°C. and worked as a plastic-like mass enabling incorporation of the additives, such as flavors, colorants and the like.
  • the boiled candy lozenge may be cut into workable portions or formed into desired shapes. A variety of forming techniques may be utilized depending upon the shape and size of the final product desired. A general discussion of the composition and preparation of hard confections may be found in H. A. Lieberman, Pharmaceutical Dosage Forms: Tablets. Volume I (1980), Marcel Dekker, Inc., New York, N.Y. at pages 339 to 469, which disclosure is incorporated herein by reference. [045]
  • the apparatus useful in accordance with the present invention comprises cooking and mixing apparatus well known in the confectionery manufacturing arts, and therefore the selection of the specific apparatus will be apparent to the artisan.
  • compressed tablet confections contain particulate materials and are formed into structures under pressure. These confections generally contain sugars in amounts up to about 95%, by weight of the composition, and typical tablet excipients such as binders and lubricants as well as flavoring agents, coloring agents and the like.
  • the pressed tablet into which the traditional Chinese medicines are incorporated may be prepared by wet granulation, dry granulation, and direct compression methods. These methods involve conventional procedures well known to the ordinary skilled artisan.
  • wet granulation involves mixing milled powders, preparing a wet mass by blending the milled powders with a binder solution, coarse screening the wet mass and drying the moist granules, screening the granules through a 14 to 20 mesh screen, mixing the screened granules with lubricants and disintegrate agents and finally tablet compressing the mass.
  • dry granulation generally involves milling of powders, compression into large hard tablets to make slugs, screening of slugs, mixing with lubricants and disintegrating agents and finally tablet compression. In the direct compression method, the milled ingredients are mixed and then merely tabletted by compression.
  • the lozenges of the present invention may be made of soft confectionery materials such as those contained in nougat.
  • the preparation of soft confections, such as nougat involves conventional methods, such as the combination of two primary components, namely (1) a high boiling syrup such as a corn syrup, hydrogenated starch hydrolysate or the like, and (2) a relatively light textured frappe, generally prepared from egg albumin, gelatin, vegetable proteins, such as soy derived compounds, sugarless milk derived compounds such as milk proteins, and mixtures thereof.
  • the frappe is generally relatively light, and may, for example, range in density from about 0.5 to about 0.7 grams/cc.
  • the high boiling syrup, or "bob syrup” of the soft confectionery is relatively viscous and has a higher density than the frappe component, and frequently contains a substantial amount of carbohydrate bulking agent such as a hydrogenated starch hydrolysate.
  • carbohydrate bulking agent such as a hydrogenated starch hydrolysate.
  • the final nougat composition is prepared by the addition of the "bob syrup” to the frappe under agitation, to form the basic nougat mixture. Further ingredients such as flavoring agents, additional carbohydrate bulking agent, coloring agents, preservatives, medicaments, mixtures thereof and the like may be added thereafter also under agitation.
  • a general discussion of the composition and preparation of nougat confections may be found in B. W. Minif ⁇ e, Chocolate, Cocoa and Confectionery: Science and Technology, 2nd edition, AVI Publishing Co., Inc., Westport, Conn. (1980), at pages 424-425, which disclosure is incorporated herein by reference.
  • the procedure for preparing the soft confectionery involves known procedures.
  • the frappe component is prepared first and thereafter the syrup component is slowly added under agitation at a temperature of at least about 65°C, and preferably at least about 100°C.
  • the mixture of components is continued to be mixed to form a uniform mixture, after which the mixture is cooled to a temperature below 80°C, at which point, the flavoring agent may be added.
  • the mixture is further mixed for an additional period until it is ready to be removed and formed into suitable confectionery shapes.
  • Chewable traditional Chinese medicine candy is prepared by procedures similar to those used to make soft confectionery. In a typical procedure, a boiled sugar-corn syrup blend is formed to which is added a frappe mixture.
  • the boiled sugar-corn syrup blend may be prepared from sugar and corn syrup blended in parts by weight ratio of about 90:10 to about 10:90.
  • the sugar- corn syrup blend is heated to temperatures above about 120°C. to remove water and to form a molten mass.
  • the frappe is generally prepared from gelatin, egg albumin, milk proteins such as casein, and vegetable proteins such as soy protein, and the like, which is added to a gelatin solution and rapidly mixed at ambient temperature to form an aerated sponge like mass.
  • the frappe is then added to the molten candy mass and mixed until homogeneous at temperatures between about 65°C. and about 120°C.
  • the ingestible traditional Chinese medicine composition of the invention can then be added to the homogeneous mixture as the temperature is lowered to about 65°C.-95°C. whereupon additional ingredients can then be added such as flavoring agents and coloring agents.
  • additional ingredients can then be added such as flavoring agents and coloring agents.
  • the formulation is further cooled and formed into pieces of desired dimensions.
  • the present invention provides improved methods for delivering traditional Chinese medicines or their hydrophilic or hydrophobic solvent extracts, 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.
  • 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.
  • 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. However, at this level 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 3 grams.
  • 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 0 C and 40% soluble in boiling water. This gives caffeine a moderately slow release as shown below:
  • the 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.
  • the traditional Chinese medicine or its hydrophilic or hydrophobic solvent extract will normally have 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), soothes the throat, reduces internal heat, prevents oxi cation of LDL leading to arterial plaque build up, antibacterial activity in the oral cavity, or 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
  • soothes the throat reduces internal heat
  • prevents oxi cation of LDL leading to arterial plaque build up, antibacterial activity in the oral cavity or has an effect on the brain chemistry of molecules that determine mood and behavior.
  • the active agent may be any agent that is traditionally used as a medicament and lends itself
  • VSC Volatile sulfur compounds
  • methyl mercaptan and dimethyl sulfide are the principal materials that impart malodor.
  • the malodorous volatile sulfuric compounds are generated through the metabolic activities of oral microorganisms on proteinaceous materials from food or saliva. Gram negative bacteria predominantly at the dorsum of the tongue are considered to be the most important group of microorganisms in the production of oral malodor.
  • Treatments of oral malodor are often based on the following three principles: (1) masking malodor by flavors; (2) complex the VSC to form non- volatile substances; (3) kill the germs that cause bad breath.
  • control of salivary bacteria is considered to be the best.
  • Many TCMs can be effectively used for controlling oral bacteria.
  • MIC Concentration test
  • MBC Minimum Bactericidal Concentration test
  • the TCM extract was added to a Schaedler broth supplemented by 1 ppm of Vitamin K and 10 ppm Hemin. The solution was then serially diluted two-fold so that each subsequent dilution contained 50% of the compound concentration of the previous dilution while maintaining a constant level of nutrients for each dilution. These dilutions were inoculated with representative oral microorganisms, and incubated for 24hrs at 37°C. For each TCM compound, the lowest dilution that was not turbid was registered as the MIC.
  • the MBC was determined by transferring 10 um of liquid from no-turbid tubes to fresh growth media and incubated for 48 hrs. For each TCM extract, the lowest dilution that did not demonstrate growth was considered as the MBC.
  • Table A & B list the MIC and MBC data on P. gingiva ⁇ is, F. niicleatum and S. mutans.
  • 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.
  • the medicament is an analgesic
  • the chewing gum would be taken on an as needed basis.
  • the agent is a stimulant, comparable to caffeine to be used to enhance performance, then 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 cyclainates. 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).
  • sweeteners more specifically high intensity sweeteners such as thaumatin, dihydrochalcones, acesulfame K, aspartame, N substituted APM derivatives such as neotame, sucralose, alitame, saccharin and cyclainates. 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 sweeten
  • 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. Although all of these materials are possible for encapsulation of active agents such as caffeine, only food grade materials should be considered.
  • Two standard food grade coating materials that are good film formers but not water soluble are shellac and Zein.
  • Others which are more water soluble, but good film formers are materials like agar, alginates, a wide range of cellulose derivatives like ethyl cellulose, methyl cellulose, sodium hydroxymethyl cellulose, and hydroxypropylmethyl cellulose, dextrin, gelatin, and modified starches. These ingredients, which are generally approved for food use, may give a fast release when used as an encapsulant.
  • Other 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. Preferably, 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.
  • 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. Even though the agglomerated active agent is only partially coated, when the quantity of coating is increased compared to the quantity of the active agent, the release can also be modified.
  • the level of coating used in the agglomerated product is a minimum of about 5%. Preferably, the coating level is a minimum of about 15% and more preferably about 20%.
  • 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.
  • 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. Generally 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. Generally, 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 0 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 U.S. Patent No. 4,978,537, which is hereby incorporated by reference.
  • 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.
  • Medicament actives may be combined in a chewing gum. In a stick 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 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 RA. S. Breslin and G.K. Beceuchenp from Monell Chemical Senses Center, Philadelphia, Pennsylvania.
  • sodium salts discussed are sodium acetate and sodium gluconate. Other sodium salts that may also be effective are sodium glycinate, sodium ascorbate and sodium glycerophosphate. 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. [090] 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/Ungual 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, pinene, 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, pinene, 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.
  • some 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 hydrophilic gum base and more quickly from a lipophilic gum base.
  • oil miscible medicaments may release more quickly when using a highly hydrophilic gum base and more slowly from a lipophilic 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.
  • Other 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.
  • alkaline materials such as sodium bicarbonate or sodium hydroxide may make the saliva slightly alkaline, which may increase buccal/Ungual 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.
  • 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. On the other hand, 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. [098] 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 tableted 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. 0221 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.
  • the previously described encapsulated, agglomerated or absorbed active agent may readily be added to a chewing gum composition.
  • the remainder of the chewing gum ingredients are well known to those of skill in the art and are not intended to be limiting to the present invention. That is, the treated particles of active agent can be added to conventional chewing gum formulations in a conventional manner.
  • Treated active agent may be added to a sugar chewing gum or a sugarless chewing gum.
  • 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 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.
  • fatty acids e.g. stearic, palmitic, oleic and linoleic acids
  • 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. BuUs 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, galactose, 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.
  • 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 calorie 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).
  • other low calorie bulking agents can be used.
  • 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/emulsif ⁇ er 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/emulsif ⁇ er 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.
  • 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 emulsif ⁇ ers 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 (often high shear) mixing of difficult-to-blend ingredients such as elastomer, filler, elastomer plasticizer, base softeners/emulsif ⁇ ers and sometimes wax, and typically requires long mixing times.
  • 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 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 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.
  • 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 arc 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 gum product.
  • 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.
  • Some film polymers can use water as the solvent in film coating. Recent advances in polymer research and in film coating technology eliminates the problem associated with the use of solvents in coating. These advances make it possible to apply aqueous films to a pellet or chewing gum product.
  • Some active agents can be added to this aqueous film or even the alcohol solvent film, in which an active agent is highly soluble. This film may also contain a flavor along with a polymer and plasticizer. The active agent can also be dissolved in the aqueous solvent and coated on the surface with the aqueous film. This will give a unique sweetness release to a film coated product.
  • a hard shell sugar or polyol coating may then be applied over the film coated product.
  • 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 0.1 % to about 1.0%, and preferably from about 0.3% to about 0.6% of the agent.
  • 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 0 F to about 24O 0 F. Preferably, 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 115 0 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. Generally, the coating syrup is very hot, about 130° to 200°F, and the flavor may volatilize if preblended with the coating syrup too early. [0148] 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.
  • 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 arc 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.
  • 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.
  • 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.
  • Wolfberry extract is an active medicament used as an oral anesthetic for sore throat. These formulas give a 3 gram stick with 3 mg of Wolfberry extract.
  • Wolfberry extract powder can be added directly to the gum.
  • a 1 gram quantity of Wolfberry extract can be dissolved in 9 grams of water giving a 10% solution and added to gum.
  • a 1 gram quantity of Wolfberry extract can be dissolved in 9 grams of water and mixed with 10 grams of glycerin and added to the gum.
  • a 1 gram quantity of Wolfberry extract is mixed with 19 grams of propylene glycol giving a 5% solution and added to gum.
  • a 1 gram quantity of Wolfberry extract is dissolved in 9 grams of ethanol, which is then mixed with 90 grams of peppermint flavor and added to gum.
  • a 1 gram quantity of Wolfberry extract is dissolved in 168 grams of corn syrup and added to chewing gum.
  • Wolfberry extract can be dissolved in water and emulsifiers can be added to the aqueous solution.
  • Example solutions can be prepared by dissolving 10 grams of Wolfberry extract 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 Wolfberry extract 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 Wolfberry extract 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 Wolfberry extract in low-moisture sugar formulations showing less than 2% theoretical moisture:
  • Examples 25-28 in Table 4 demonstrate the use of Wolfberry extract in medium-moisture sugar formulations having about 2% to about 5% moisture.
  • Examples 29-32 in Table 5 demonstrate the use of Wolfberry extract in high-moisture sugar formulations having more than about 5% moisture.
  • Examples 33-36 in Table 6 and Examples 37-44 in Tables 7 and 8 demonstrate the use of Wolfberry extract 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 9 shows sugar chewing formulations that can be made with various types of sugars.
  • Table 10 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 3, 4, 5, 6, 7, 8, 9 and 10. Since Wolfberry extract 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 Wolfberry extract powder mixture is obtained by spray drying an appropriate ratio alcohol/shellac/Wolfberry extract mixture at 10% solids.
  • Example 70 - A 70% Zein, 30% active Wolfberry extract powder mixture is obtained by spray drying an alcohol/Zein/Wolfberry extract mixture at
  • Example 71 - A 40% shellac, 60% active Wolfberry extract powder mixture is obtained by fluid-bed coating Wolfberry extract with an alcohol/shellac solution at 20% solids.
  • Example 72 - A 40% Zein, 60% active Wolfberry extract powder mixture is obtained by fluid-bed coating Wolfberry extract with an alcohol/Zein solution of 20% solids.
  • Example 73 A 70% wax, 30% active Wolfberry extract powder mixture is obtained by spray chilling a mixture of molten wax and Wolfberry extract.
  • Example 74 - A 70% Zein, 30% active Wolfberry extract powder mixture is obtained by spray drying an aqueous mixture of Wolfberry extract and
  • Examples 69-74 would all give nearly complete encapsulation and would delay the release of Wolfberry extract 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. [0183] Other polymers that are more water soluble would have less of an effect of delaying the release of the Wolfberry extract if used in the coating.
  • Example 75 A 30% hydroxpropylmethyl cellulose (HPMC), 70%
  • Wolfberry extract powder mixture is obtained by fluid-bed coating Wolfberry extract with an aqueous solution of HPMC at 10% solids.
  • Example 76 A 50% maltodextrin, 50% active Wolfberry extract powder mixture is obtained by spray drying an aqueous mixture of Wolfberry extract and maltodextrin at 20% solids.
  • Example 77 ⁇ A 40% gum arabic, 60% active Wolfberry extract powder mixture is obtained by fluid-bed coating Wolfberry extract with an aqueous solution of gum arabic at 20% solids.
  • Example 78 A 15% hydroxypropylmethyl cellulose (HPMC), 85% active Wolfberry extract powder mixture is prepared by agglomerating Wolfberry extract 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 Wolfberry extract powder mixture is made by agglomerating Wolfberry extract 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 arc 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 Wolfberry extract 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. Wolfberry extract 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 Wolfberry extract total piece must contain 0.2%.
  • Wolfberry extract can then be used in the coating formula on the various pellet gum formulations, as well as on various other confections such as hard candies, chewy candies, nougats, and the like.
  • Table 12 shows some sugar and dextrose type formulas: 196]
  • Examples 96-99 gum arabic is blended in the sugar syrup.
  • examples 100 and 101 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.
  • Wolfberry extract 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. Wolfberry extract 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.
  • Wolfberry extract 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 Wolfberry extract 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. al
  • the high intensity sweetener used is aspartame.
  • high intensity such as alitame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin and combinations thereof may be used in any of the examples with the level adjusted for sweetness.
  • 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.
  • Wolfberry extract may be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol. The following table gives formulas for a xylitol coating:
  • erythritol may be substituted for xylitol in Table 14. In some cases more gum arabic may be needed to give good binding.
  • 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. Wolfberry extract may be applied in a similar manner as in the previous xylitol coating or may be preblended with the dry charge material. After all coating is applied and dried, talc and wax are added to give a polish. [0208] In a similar manner, 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. In the later stages of the coating process, less gum arabic could be used and a more pure polyol syrup could be used to give a smooth surface. Also, the dry charge would only be used in the early stages of the coating process.
  • other 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 Wolfberry extract, gum talha, gum arabic or other moisture absorbing materials. Also, 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 Chinese hawthorn extract can be added to gum after it is dissolved in water or mixed with various aqueous solvents.
  • Chinese hawthorn extract is an active medicament used as an antihistamine. These formulas give a 3 gram stick with 4 mg of Chinese hawthorn extract.
  • a 1 gram quantity of Chinese hawthorn extract can be dissolved in 9 grams of water giving a 10% solution and added to gum.
  • a 1 gram quantity of Chinese hawthorn extract can be dissolved in 9 grams of water and mixed with 10 grams of glycerin and added to the gum.
  • a 1 gram quantity of Chinese hawthorn extract is mixed with 19 grams of glycerin giving a 5% solution and added to gum.
  • a 1 gram quantity of Chinese hawthorn extract is mixed with 9 grams of peppermint flavor giving a 10% solution and added to gum.
  • a 1 gram quantity of Chinese hawthorn extract is dissolved in 9 grams of ethanol, which is then mixed with 90 grams of peppermint flavor and added to gum.
  • a 1.3 gram quantity of Chinese hawthorn extract is dissolved in 168 grams of corn syrup and added to chewing gum.
  • Example solutions can be prepared by dissolving 13 grams of Chinese hawthorn extract in 72 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 135 uses a mixture of Chinese hawthorn extract and water with no emulsif ⁇ er. The HLB value of the emulsifiers used in Examples 136-140 are listed in Table 17.
  • Examples 151 - 154 in Table 19 demonstrate the use of Chinese hawthorn extract in medium-moisture sugar formulations having about 2% to about 5% moisture.
  • Examples 155-158 in Table 20 demonstrate the use of Chinese hawthorn extract 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 Chinese hawthorn extract 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 24 shows sugar chewing formulations that can be made with various types of sugars.
  • 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 Chinese hawthorn extract 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.
  • Gum center formulas may or may not contain Chinese hawthorn extract.
  • Formulations with or without Chinese hawthorn extract 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. Chinese hawthorn extract 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 Chinese hawthorn extract total piece must contain 0.27%. [0235] Chinese hawthorn extract can be used in the coating formula on the various pellet gum formulations. The following Table 27 shows some sugar and dextrose type formulas:
  • 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.
  • Chinese hawthorn extract 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. Chinese hawthorn extract 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.
  • Chinese hawthorn extract 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 Chinese hawthorn extract 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.
  • the high intensity sweetener used is aspartame.
  • high intensity such as alitame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin and combinations thereof may be used in any of the examples with the level adjusted for sweetness.
  • 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.
  • Chinese hawthorn extract may be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol. The following table gives formulas for a xylitol 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. 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 whiten er 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. Chinese hawthorn extract may be applied in a similar manner as in the previous xylitol coating, or may be preblended with the dry charge material. [0244] In a similar manner, 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. In the later stages of the coating process, less gum arabic could be used and a more pure polyol syrup could be used to give a smooth surface. Also, the dry charge would only be used in the early stages of the coating process.
  • other 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 Wolfberry extract, gum talha, gum arabic or other moisture absorbing materials. Also, 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.
  • Honeysuckle extract is an active medicament used for reducing internal heat or antibacterial effects. These formulas give a 3 gram stick with 30 mg of Honeysuckle extract.
  • a 20 gram quantity of Honeysuckle extract can be dissolved in 80 grams of water giving a 20% solution and added to gum.
  • a lO gram quantity of Honeysuckle extract 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 Honeysuckle extract is mixed with 90 grams of glycerin giving a 10% solution and added to gum.
  • a 10 gram quantity of Honeysuckle extract is mixed with 90 grams of propylene glycol giving a 10% solution and added to gum.
  • Honeysuckle extract can be dissolved in water and emulsifiers can be added to the aqueous solution.
  • Example solutions can be prepared by dissolving 20 grams of Honeysuckle extract 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 Honeysuckle extract 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 Honeysuckle extract 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 Huang Qi extract in low-moisture sugar formulations showing less than 2% theoretical moisture:
  • Examples 248-251 in Table 34 demonstrate the use of Huang Qui extract extract in medium-moisture sugar formulations having about 2% to about 5% moisture.
  • Examples 252-255 in Table 35 demonstrate the use of Huang Qui extract in high-moisture sugar formulations having more than about 5% moisture.
  • Examples 256-259 in Table 36 and Examples 260-267 in Tables 37 and 38 demonstrate the use of Loquat Leaf extract 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 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 Honeysuckle extract 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 Honeysuckle extract 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. Honeysuckle extract 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 Honeysuckle extract in two gum pieces, total piece must contain 1.0%. [0271] Honeysuckle extract can be used in the coating formula on the various pellet gum formulations. The following Table 42 shows some sugar and dextrose type formulas:
  • 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.
  • Honeysuckle extract 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. Honeysuckle extract 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.
  • sugar or dextrose may be added as a dry charge, which may also contain the active.
  • 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.
  • Honeysuckle extract 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 Honeysuckle extract similar to those found in Tables 33-38 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 44.
  • the high intensity sweetener used is aspartame.
  • high intensity such as alitame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin and combinations thereof may be used in any of the examples with the level adjusted for sweetness.
  • Lycasin and other polyols such as maltitol, erythritol, xylitol, lactitol and hydrogenated isomaltulose may also be used in the gum center formulations at various levels similar to those shown in Table 40.
  • 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.
  • Honeysuckle extract may be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol. The following table gives formulas for a xylitol 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. 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. After all coating is applied and dried, talc and wax are added to give a polish.
  • Honeysuckle extract may be applied in a similar manner as in the previous xylitol coating examples, 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 46 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. In the later stages of the coating process, less gum arabic could be used and a more pure polyol syrup could be used to give a smooth surface. Also, the dry charge would only be used in the early stages of the coating process.
  • other 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 arabinogalactan, gum talha, gum arabic or other moisture absorbing materials. Also, 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.
  • Liquid flavors generally are not added throughout the coating but at specific points throughout the process. When flavor is added, less air is used for drying until the flavor coating is covered by the next coatings and dried. Flavors may be various spearmint, peppermint, wintergreen, cinnamon, and fruit flavors to yield a wide variety of flavored chewing gum products.
  • 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.
  • Formulations with or without Ginger powder can also be made similar to those found in previous tables 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 previous tables. Ginger powder may be added to a gum center only, into a gum coating with more in the center or to both center and coating. [0290] Ginger powder can be used in the coating formula on the various pellet gum formulations. The following Table 48 shows some sugar and dextrose type formulas:
  • 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.
  • Ginger powder 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. Ginger powder or oil may also be premixed with the flavor. After the final coats are applied and dried, wax is applied to give a smooth polish.
  • gum arabic is blended in the sugar syrup.
  • gum arabic powder is dry charged after 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.
  • Ginger powder or oil may also be used in coating of sugarless gum centers.
  • the base formulation can be increased in proportion to the amount of coating applied to the center.
  • Formulations with and without ginger powder chloride similar to those found in previous tables 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.
  • the high intensity sweetener used is aspartame.
  • high intensity such as alitame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin and combinations thereof may be used in any of the examples with the level adjusted for sweetness.
  • Lycasin and other polyols such as maltitol, xylitol, erythritol, lactitol and hydrogenated isomaltulose may also be used in the gum center formulations at various levels.
  • 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.
  • Ginger powder or oil may be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • xylitol sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • 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. After all coating is applied and dried, talc and wax are added to give a polish. Ginger powder or oil may be applied in a similar manner as in the previous xylitol coating examples, or preblended with the dry charge materials. [0301] In a similar manner, coatings with sorbitol, lactitol, and hydrogenated isomaltulose may be made in the coating formulas in Table 52 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. In the later stages of the coating process, less gum arabic could be used and a more pure polyol syrup could be used to give a smooth surface. Also, the dry charge would only be used in the early stages of the coating process.
  • other 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 arabinogalactan, gum talha, gum arabic or other moisture absorbing materials. Also, powdered sweeteners or flavors could be added with the dry charge.
  • Some polyols such as sorbitol, maltitol, erythritol, lactitol, 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.
  • Liquid flavors generally are not added throughout the coating but at specific points throughout the process. When flavor is added, less air is used for drying until the flavor coating is covered by the next coatings and dried. Flavors may be various spearmint, peppermint, wintergreen, cinnamon, and fruit flavors to yield a wide variety of flavored chewing gum products.
  • 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.
  • chuang lian extract denoted chuang lian, or coptis chinensis
  • Chuang lian is an antibacterial effective against oral bacteria responsible for caries and halitosis. These formulas give a 1.5 gram piece containing 12.5 mg of chuang lian or 0.83% of the total gum product. Gum center formulas may or may not contain encapsulated or controlled release chuang lian.
  • Formulations with or without chuang lian can also be made similar to those found in previous tables 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 previous tables chuang lian may be added to a gum center only, into a gum coating with none in the center, or to both center and coating. [0309] Chuang lian can be used in the coating formula on the various pellet gum formulations. The following Table 54 shows some sugar and dextrose type formulas:
  • 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.
  • Chuang Lian 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. Chuang Lian may also be premixed with the flavor. After the final coats are applied and dried, wax is applied to give a smooth polish.
  • gum arabic is blended in the sugar syrup.
  • gum arabic powder is dry charged after 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.
  • CHUANG LIAN 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 CHUANG LIAN similar to those found in previous tables 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 56.
  • the high intensity sweetener used is aspartame.
  • high intensity such as alitame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin and combinations thereof may be used in any of the examples with the level adjusted for sweetness.
  • Lycasin and other polyols such as maltitol, xylitol, erythritol, lactitol and hydrogenated isomaltulose may also be used in the gum center formulations at various levels.
  • 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.
  • Chuang Lian may be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • the following table gives formulas for a xylitol coating:
  • 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.
  • 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. Chuang lian may be applied in a similar manner as in the previous xylitol coating examples, or preblended with the dry charge material and added to the coating. [0320] In a similar manner, coatings with sorbitol, lactitol, and hydrogenated isomaltulose may be made in the coating formulas in Table 58 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. In the later stages of the coating process, less gum arabic could be used and a more pure polyol syrup could be used to give a smooth surface. Also, the dry charge would only be used in the early stages of the coating process.
  • other 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 arabinogalactan, gum talha, gum arabic or other moisture absorbing materials. Also, powdered sweeteners or flavors could be added with the dry charge.
  • Some polyols such as sorbitol, maltitol, erythritol, lactitol, 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 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.
  • Formulations with or without L. Erythrorhizon can also be made similar to those found previously in Tables 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 previous tables. L. Erythrorhizon may be added to the gum center only, into a gum coating with none in the center, or both center and coating. [0327] L. Erythrorhizon can then be used in the coating formula on the various pellet gum formulations. The following Table 60 shows some sugar and dextrose type formulas:
  • 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.
  • L. Erythrorhizon 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. L. Erythrorhizon may also be premixed with the flavor. After the final coats are applied and dried, wax is applied to give a smooth polish.
  • 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.
  • L. Erythrorhizon 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 L. Erythrorhizon similar to those found in previous tables 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 center formulas are in Table 62.
  • the high intensity sweetener used is aspartame.
  • high intensity such as alitame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin and combinations thereof may be used in any of the examples with the level adjusted for sweetness.
  • Lycasin and other polyols such as maltitol, xylitol, erythritol, lactitol and hydrogenated isomaltulose may also be used in the gum center formulations at various levels.
  • 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.
  • L. Erythrorhizon may be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • xylitol sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol.
  • 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 active may be premixed with the dry charge material. The following formulations may be used.
  • Maltitol powder is used to dry charge in the early stages of coating. Maltitol, gum arabic, and whitener is blended into a syrup and applied to pellets. After all coating is applied and dried, talc and wax are added to give a polish. L. Erythrorhizon may be applied in a similar manner as the previous xylitol examples, or added with the dry charge material.
  • coatings with sorbitol, lactitol, and hydrogenated isomaltulose may be made in the coating formulas in Table 64 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 arabinogalactan, 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, erythritol, lactitol, 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 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.
  • Formulations can also be made similar to those found in previous tables for low, medium, and high moisture formulas. Higher levels of base may be used with a corresponding decrease in other ingredients. Also, other sugars may be used in the gum center as found in previous tables.
  • Bloat Fruit seeds ground or there extracts (Denoted Bloat in the examples) can then be used in the coating formula on the various pellet gum formulations. Bloat relieves coughing and reduces internal heat, and throat irritation.
  • Table 66 shows some sugar and dextrose type formulas: Using a 1 gram center, the levels of Bloat in the following tables will give 250-800 mg per 2 pieces in 1.5-3.0 gum pieces with 33 to 50% coating.
  • 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 and/or calcium carbonate in this syrup. Flavor is not mixed with the hot syrup, but added at low levels with one or more coats. After the final coats are applied and dried, wax is applied to give a smooth polish.
  • 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.
  • Gum arabic 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 similar to those found in previous tables 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 68.
  • the high intensity sweetener used is aspartame.
  • other high intensity sweetener such as alitame, acesulfame K, salts of acesulfame, cyclamate and its salts, saccharin and its salts, neotame, sucralose, thaumatin, monellin, dihydrochalcone, stevioside, glycyrrhizin and combinations thereof may be used in any of the examples with the level adjusted for sweetness.
  • Lycasin and other polyols such as maltitol, xylitol, erythritol, lactitol and hydrogenated isomaltulose may also be used in the gum center formulations at various levels similar to those shown previously. 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.
  • Bloat can be used in sugarless coatings with xylitol, sorbitol, maltitol, lactitol, hydrogenated isomaltulose and erythritol. Gum arabic acts as a binder, film former, hardener of the coated pellet. The following table gives formulas for a xylitol coating:
  • erythritol coating also requires a binder, film former, and hardener in the coating to make an acceptable product.
  • the following formulations can be made:
  • 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 is blended into a syrup and applied to pellets. Bloat may be applied with the syrup suspension, preblended with powder maltitol or added as a dry charge. After all coating is applied and dried, talc and wax are added to give a polish.
  • coatings with sorbitol, lactitol, and hydrogenated isomaltulose may be made in the coating formulas in Table 71 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, magnesium carbonate, starches, gums like arabinogalactan, 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, 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.
  • Liquid flavors generally are not added throughout the coating but at specific points throughout the process. When flavor is added, less air is used for drying until the flavor coating is covered by the next coatings and dried. Flavors may be various spearmint, peppermint, wintergreen, cinnamon, and fruit flavors to yield a wide variety of flavored chewing gum products. Candy Examples Pressed Mint Examples
  • Healthful chewing gums of the present invention were made according to the formulas of Examples 523 - 528.
  • aloe arborescens whole leaf powder can be used at a level of 0.03 to 0.50% by weight of the finished gum product.
  • spray dried extract of barbary wolfberry fruit can be used at a level of 0.03 to 0.50% by weight of the finished gum product.
  • spray dried extract of loquat fruit and spray dried extract of luo han guo can be used in combination at levels of 0.03 to 0.50% and 0.50 to 2.00% respectively by weight of the finished gum product.
  • the chewing gums of Examples 530 - 535 can be formed into pellets and coated to a coating level of 32% according to the formula of Example 529.
  • green tea extract can be used at a level of 0.03 to 1.00% and pomegranate fruit spray dried extract can be used at a level of 0.03 to 3.00%. These extracts can be used separately or, more advantageously, in combination as antioxidants to reduce free radicals and enhance the appearance of skin.
  • mulberry leaf, chrysanthemum and Radix platycodonis extracts may be used at a level of 0.03 to 0.50%. These extracts may be used separately or, more advantageously, in combination to reduce internal heat and sooth irritated throats.
  • spine date seed extract and rose extracts may be used at a level of 0.03 to 0.50%. These extracts may be used separately or, more advantageously, in combination to reduce stress and promote relaxation.
  • oolong tea extracts may be used at a level of 0.03 to 2.00% preferably in combination with ginseng flavor to increase alertness and mental functioning.
  • compositions and methods of the present invention are capable of being incorporated in the form of a variety of embodiments, only a few of which have been illustrated and described above.
  • the invention may be embodied in other forms without departing from its spirit or essential characteristics.
  • the described embodiments are to be considered in all respects only as illustrative and not restrictive, and the scope of the invention, therefore, indicated by the appended claims rather than by the foregoing description. AU changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

Abstract

L'invention concerne un procédé servant à produire un chewing-gum permettant une libération contrôlée d'un agent actif de la médecine traditionnelle chinoise, ainsi que le chewing-gum ainsi produit, en modifiant physiquement les propriétés de libération de l'agent actif de la médecine traditionnelle chinoise par enrobage et séchage. L'agent actif de la médecine traditionnelle chinoise est enrobé par encapsulation, partiellement enrobé par agglomération, emprisonné par absorption ou traité par de multiples étapes d'encapsulation, d'agglomération et d'absorption. L'agent actif de la médecine traditionnelle chinoise enrobé est de préférence ensuite co-séché et classifié à une certaine granulométrie pour produire un agent actif de la médecine traditionnelle chinoise à libération modifiée destiné à être utilisé dans un chewing-gum. L'agent actif de la médecine traditionnelle chinoise peut également être utilisé dans un enrobage sur un produit de type chewing-gum, en tant que partie d'un composé de laminage appliqué sur le produit de type chewing-gum ou en tant que partie du liquide dans un produit de type chewing-gum ayant un cœur liquide.
PCT/US2007/060583 2006-10-11 2007-01-16 Véhicules d'administration orale contenant un médicament traditionnel chinois ou un extrait de celui-ci WO2008045579A1 (fr)

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US12/444,680 US20100104518A1 (en) 2006-10-11 2007-01-16 Chewing gum, confection, and other oral delivery vehicles containing a traditional chinese medicine or extract thereof
EP07710146A EP2083633A4 (fr) 2006-10-11 2007-01-16 Véhicules d'administration orale contenant un médicament traditionnel chinois ou un extrait de celui-ci

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US2006039687 2006-10-11

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WO2010096601A1 (fr) 2009-02-20 2010-08-26 Tredegar Film Products Corporation Film façonné ajouré hydrophile
WO2011117634A2 (fr) 2010-03-23 2011-09-29 Cadbury Uk Limited Produit de confiserie contenant des constituants actifs et/ou réactifs, et leurs procédés de production
US20120171273A1 (en) * 2009-04-28 2012-07-05 Minmin Tian Oral compositions for skin benefits
US20120288451A1 (en) * 2009-12-28 2012-11-15 Elena Yurievna Belous Means for removing tobacco tars and composition containing same
WO2013110812A1 (fr) * 2012-01-27 2013-08-01 Denali Pharma Composition sous forme d'une gelule comprenant de la poudre de gingembre et un agent enrobant
WO2014150967A1 (fr) * 2013-03-15 2014-09-25 Altria Client Services Inc. Produits énergétiques oraux comprenant de la caféine encapsulée
DE102013213596A1 (de) 2013-07-11 2015-01-15 Henkel Ag & Co. Kgaa Mund- und Zahnpflege- und -reinigungsmittel zur Zahnfleischvitalisierung
CN105675770A (zh) * 2016-04-26 2016-06-15 广西壮族自治区梧州食品药品检验所 高效液相色谱法检测蛇胆川贝液中胆酸和西贝母碱的方法
DE102009001334B4 (de) * 2009-03-04 2017-02-23 Stefan Brosig Einfache magensaftresistente Verkapselung, z.B. von Ingwer und anderen empfindlichen Stoffen
US9675542B2 (en) 2011-05-16 2017-06-13 Colgate-Palmolive Company Oral care compositions
WO2022074422A1 (fr) * 2020-10-05 2022-04-14 Stone Tree International Limited Agencement phytochimique et procédé associé
US11771644B1 (en) * 2022-07-06 2023-10-03 Zhejiang Airsun Commodity Co., Ltd. Whitening toothpaste capable of effectively removing dental plaque and tartar

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Publication number Priority date Publication date Assignee Title
WO2010096601A1 (fr) 2009-02-20 2010-08-26 Tredegar Film Products Corporation Film façonné ajouré hydrophile
DE102009001334B4 (de) * 2009-03-04 2017-02-23 Stefan Brosig Einfache magensaftresistente Verkapselung, z.B. von Ingwer und anderen empfindlichen Stoffen
US9186348B2 (en) * 2009-04-28 2015-11-17 Wm. Wrigley Jr. Company Oral compositions for skin benefits
US20120171273A1 (en) * 2009-04-28 2012-07-05 Minmin Tian Oral compositions for skin benefits
US20120288451A1 (en) * 2009-12-28 2012-11-15 Elena Yurievna Belous Means for removing tobacco tars and composition containing same
WO2011117634A2 (fr) 2010-03-23 2011-09-29 Cadbury Uk Limited Produit de confiserie contenant des constituants actifs et/ou réactifs, et leurs procédés de production
US9295269B2 (en) 2010-03-23 2016-03-29 Reading Scientific Services Limited Confectionery product containing active and/or reactive components and methods of productions thereof
US9675542B2 (en) 2011-05-16 2017-06-13 Colgate-Palmolive Company Oral care compositions
WO2013110812A1 (fr) * 2012-01-27 2013-08-01 Denali Pharma Composition sous forme d'une gelule comprenant de la poudre de gingembre et un agent enrobant
FR2986136A1 (fr) * 2012-01-27 2013-08-02 Denali Pharma Composition sous forme d'une gelule comprenant de la poudre de gingembre et un agent enrobant
WO2014150967A1 (fr) * 2013-03-15 2014-09-25 Altria Client Services Inc. Produits énergétiques oraux comprenant de la caféine encapsulée
US10149850B2 (en) 2013-03-15 2018-12-11 Altria Client Services Llc Oral energy products including encapsulated caffeine
US11020401B2 (en) 2013-03-15 2021-06-01 Altria Client Services Llc Oral energy products including encapsulated caffeine
EP2845584A1 (fr) 2013-07-11 2015-03-11 Henkel AG&Co. KGAA Agent de nettoyage buccal et de soin dentaire pour la revitalisation de la gencive
DE102013213596A1 (de) 2013-07-11 2015-01-15 Henkel Ag & Co. Kgaa Mund- und Zahnpflege- und -reinigungsmittel zur Zahnfleischvitalisierung
CN105675770A (zh) * 2016-04-26 2016-06-15 广西壮族自治区梧州食品药品检验所 高效液相色谱法检测蛇胆川贝液中胆酸和西贝母碱的方法
WO2022074422A1 (fr) * 2020-10-05 2022-04-14 Stone Tree International Limited Agencement phytochimique et procédé associé
US11771644B1 (en) * 2022-07-06 2023-10-03 Zhejiang Airsun Commodity Co., Ltd. Whitening toothpaste capable of effectively removing dental plaque and tartar

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