EP1954250A2 - Filme und kapseln aus modifizierten carboxy-methylcellulose-materialien und herstellungsverfahren - Google Patents

Filme und kapseln aus modifizierten carboxy-methylcellulose-materialien und herstellungsverfahren

Info

Publication number
EP1954250A2
EP1954250A2 EP06827160A EP06827160A EP1954250A2 EP 1954250 A2 EP1954250 A2 EP 1954250A2 EP 06827160 A EP06827160 A EP 06827160A EP 06827160 A EP06827160 A EP 06827160A EP 1954250 A2 EP1954250 A2 EP 1954250A2
Authority
EP
European Patent Office
Prior art keywords
capsule
film
polymeric additive
mixtures
films
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP06827160A
Other languages
English (en)
French (fr)
Inventor
Andries Hanzen
Henrica Wilhelmina Cornelia Vaessen-Van Hoven
Anja Maria Christina Petronella Hopman
Ross Clark
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CP Kelco US Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US11/264,260 external-priority patent/US20070098779A1/en
Priority claimed from US11/264,262 external-priority patent/US20070166371A1/en
Application filed by Individual filed Critical Individual
Publication of EP1954250A2 publication Critical patent/EP1954250A2/de
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B11/00—Preparation of cellulose ethers
    • C08B11/02—Alkyl or cycloalkyl ethers
    • C08B11/04—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals
    • C08B11/10—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals substituted with acid radicals
    • C08B11/12—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals substituted with acid radicals substituted with carboxylic radicals, e.g. carboxymethylcellulose [CMC]
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
    • C08L1/08—Cellulose derivatives
    • C08L1/26—Cellulose ethers
    • C08L1/28—Alkyl ethers
    • C08L1/286—Alkyl ethers substituted with acid radicals, e.g. carboxymethyl cellulose [CMC]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/04—Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds

Definitions

  • This invention relates to edible films and/or capsules for the delivery of and/or coating of active ingredients.
  • Such edible films and/or capsules comprise particular molecular weight-modified carboxymethylcellulose (CMC) materials either alone or in combination with other types of hydrocolloids, biogums, cellulose ethers, and the like.
  • CMC carboxymethylcellulose
  • the utilization of such modified CMC products aids in the production of such films and/or capsules through the availability of larger amounts of base materials with lower amounts of water requiring evaporation therefrom.
  • Films and capsules particularly of the edible variety, have been popular for the delivery of active ingredients such as pharmaceuticals, breath fresheners, oral care materials, foodstuffs, and other like products for ingestion within a person's oral cavity. Furthermore, such films are utilized within coatings, seals, and other like objects for such materials as dyes, deodorants, detergents, tablets, and the like. Flexible capsules have been utilized for pharmaceutical delivery for some time now and have proven to be invaluable, particularly for patients that exhibit difficulty in swallowing pills.
  • Such films are generally comprised of non- toxic ingredients that permit the desirable properties of quick dissolution, flexible film production, and dimensional stability for proper cutting into specific shapes and sizes.
  • Typical films of this type include pullulan, cellulosics (such as hydroxypropylmethyl cellulose), carrageenan, pectin, as well as mixtures of certain low molecular weight varieties of products and high molecular weight types.
  • clarity and low tackiness are generally properties sought after by the consumer. Clear, transparent films give an appearance of uniformity and order, whereas the utilization of a tacky film will most likely result in a film that will dissolve only after sticking to the user's palate for an extended period of time. Furthermore, tackiness may also lend itself to packed films that adhere to one another, thus increasing the likelihood of simultaneous use of multiple films or damage to films during removal from the packaging in which such products are stored. Thus, low tackiness is desirable for such film products.
  • the closest prior art teaches edible, consumable films for the delivery of certain actives, such as flavoring and/or breath freshening agents, that are formulated to dissolve in the user's oral cavity.
  • Such prior art includes films made from water soluble polymer such as pullulan or hydroxypropylmethyl cellulose and an essential oil selected from thymol, methyl salicylate, eucalyptol and/or menthol; film compositions containing therapeutic and/or breath freshening agents, prepared from water soluble polymers such as hydroxypropylmethyl cellulose, hydroxypropylcellulose, etc., and a polyalcohol (such as polyglycols); as well as consumable films that comprise hydroxyalkylmethylcellulose, pre-gelatinized starch, and a flavoring agent.
  • water soluble polymer such as pullulan or hydroxypropylmethyl cellulose and an essential oil selected from thymol, methyl salicylate, eucalyptol and/or menthol
  • Relative humidity may pose a problem for such films and/or capsules during production as well as thereafter (such as during shelf storage), and polysaccharides, such as CMC, hydroxypropylmethylcellulose, and the like, all seem to suffer certain drawbacks as a result of water content, not to mention the presence of too much salt within the target environment.
  • polysaccharides such as CMC, hydroxypropylmethylcellulose, and the like
  • this invention encompasses a novel film and/or capsule comprising modified CMC materials exhibiting a molecular weight range of from 1500 to 75000 and a degree of substitution of less than about 1.5.
  • this invention encompasses a method of producing such a film and/or capsule comprising the steps of a) providing a CMC materials exhibiting a molecular weight range of from 80000 to 3000000 and degree of substitution of less than about 1.5; b) degrading said CMC materials by exposing said materials to an enzyme in an amount and for a period of time sufficient to reduce the molecular weight range of said CMC materials to a range of from 1500 to 75000; c) inactivating said enzyme; d) producing a solution of the resultant modified CMC materials of step "b" with at most 70% by weight of water and optionally including at most 12.5 % of a plasticizer; and e) forming a film or capsule through proper application of said solution to a proper surface and allowing said water therein to evaporate therefrom.
  • Such films thus exhibit at least the same film strength, rapid film dissolution, and delivery capabilities of active ingredients as previously made films and/or capsules, but with lower manufacturing costs, and potentially reduced tackiness as those currently utilized within the pertinent markets.
  • Such an improvement has been realized through the utilization of a single modified CMC component as well, thereby permitting a reduction in manufacturing complexity of films.
  • modified CMC polymer may be utilized for this application, it is noted that combinations of the required modified CMC polymer with other polymeric additives, such as hydrocolloids, biogums, and cellulose ethers (either gel-forming or non-gelling viscosity building types, depending on the potential benefits desired from such an additive) may be practiced as well.
  • other polymeric additives such as hydrocolloids, biogums, and cellulose ethers (either gel-forming or non-gelling viscosity building types, depending on the potential benefits desired from such an additive) may be practiced as well.
  • Such a film and/or capsule, of the modified CMC alone or in combination with such other optional gel-forming or non-gelling viscosity building additives is thus highly desired from a cost perspective as well as quick and complete dissolution when exposed to sufficient moisture within the oral cavity.
  • Such a specific characteristic is advantageous since undissolved film residue imparts an unacceptable, unpalatable, slimy feel to the palate of the user.
  • film is intended to encompass a solid, flexible sheet of polymer material that has a very low ratio of thickness to area (width multiplied by length).
  • capsule is intended, for purpose of this invention, to encompass a flexible container that may be used to carry and active material into the digestive tract for later delivery of this active agent.
  • Polysaccharides such as certain cellulosic-based types (carboxymethylcellulose, as one non-limiting example), have been utilized within numerous fields for many years as viscosity modifiers, carriers, anti-redeposition agents, and other like purposes within the paper, oil, food, paint, and detergent industries, to name a few.
  • modified cellulosics water-soluble polymers have been provided as well, particularly within U.S. Pat. No. 5,569,483 to Timonen et al., as it pertains to substitution of fat within foodstuffs, and within U.S. Pat. No. and 5,543,162 to Timonen et al., as it pertains
  • the present invention relates to an edible film composition
  • an edible film composition comprising a safe and effective amount of at least a modified CMC material, optionally, a further amount of another polysaccharide or biogum material, optionally, a safe and effective amount of a plasticizing agent, and, a safe and effective amount of an ingredient, including, as examples, a flavoring agent, a pharmaceutical agent, an oral care additive, an antiinflammatory agent, an antimicrobial agent, a surfactant, a sweetener, a vitamin, and the like.
  • the films of this invention may be utilized as delivery systems for such active ingredients through dissolution within the oral cavity of a user and/or patient, or as a coating or seal for materials including, without limitation, foodstuffs, soaps, detergents, tablets, and the like, or potentially can be modified to form capsules for transport of active ingredients to the oral cavity of a user and/or patient (delivery of actives in capsules takes place in the stomach/gastro-intestinal system).
  • the edible film and/or capsule compositions of the present invention comprise at least one molecular weight-modified CMC material.
  • degradation may be accomplished through any type of well known method, such as acid, radiation, oxidation and heat degradation, preferably the degradation step is provided through enzymatic exposure.
  • the initial method step is actually providing the degrading CMC material for further use thereof.
  • Such a step may be accomplished similarly to that taught within either of the Timonen et al. patents discussed above.
  • a CMC having the desired degree of substitution and initial molecular weight is subjected to a preselected amount of cellulase enzyme in order to reduce the overall molecular weight of the CMC material itself to a level proper for film and/or capsule production.
  • the CMC selected for this step must exhibit a proper degree of substitution (i.e., the average amount of carboxymethyl groups per glucose unit) in order to permit the ultimate generation of a film and/or capsule exhibiting the requisite characteristics of rapid dissolution, dimensional stability, and low tackiness, at least.
  • the degree of substitution is preferably, though not necessarily, lower than about 0.95.
  • the initial molecular weight may be within a broad range as long as the ultimate molecular weight range meets the requirements that lead to the same type of proper film and/or capsule generation in terms of the physical characteristics noted above. Thus, an initial molecular weight range, as measured as by using GPC analysis of from 80,000 to about 3,000,000 is acceptable.
  • the thus preselected CMC starting material can then be exposed to an amount of cellulase that coincides, in combination with the amount of time of such exposure, pH and temperature with the ultimate degradation of the CMC material into individual strands thereof exhibiting a range of molecular weights from 1,500 to 75,000.
  • the molecular weight will be between about 20,000 and 50,000 for the modified CMC materials.
  • a lower molecular weight range i.e., from 1,500 to about 20,000
  • the cellulase can then be inactivated through heat exposure, as one example, thereby preventing further degradation of the CMC from occurring.
  • the enzyme can be removed from within the modified CMC solution used for film and/or capsule production.
  • the molecular weight range sought after for the modified CMC materials transfers to a viscosity measurement for the solutions used to ultimately produced the target films typically within a range of 10,000 mPas to 45,000 mPas. It has been found as well that such viscosity measurements appear to contribute to the overall effectiveness of the ultimately formed films and/or capsules in combination with the degree of substitution of the starting CMC materials themselves. Thus, it has been determined that such molecular weight and viscosity properties are critical to the success of the overall invention, at least when the sole film- forming component of the solution is the modified CMC material.
  • the modified CMC can be utilized as such a sole film-forming component.
  • Most commercially available films require the utilization of combinations of different polymers to attain desired film properties; however, it has surprisingly been determined that the modified CMC polymers utilized within this invention are sufficient on their own to achieve such results.
  • the ability to form a film and/or capsule that meets or exceeds the aforementioned physical characteristics as well as can withstand certain salt and relative humidity exposures without appreciably effecting the dimensional stability and usefulness of the ultimate end use product was unexpected.
  • a plasticizer in order to increase film flexibility or provide increases in dimensional stability and other physical characteristics of the subject films and/or capsules as well.
  • Such a molecular weight-modified CMC polymer exhibits excellent compatibility with such other possible polymers and thus their optional presence should not be problematic.
  • non-gelling viscosity building additives selected from the group consisting of cellulose ethers, such as methyl cellulose, (non-modified) carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and mixtures thereof; biogums, such as xanthan gum, diutan gum, rhamsan gum and welan gum, gellan gum, and mixtures thereof; and hydrocolloids such as carrageenan, pectin, gum arabic, guar, locust bean gum, gum tragacanth, tara gum, sodium alginate, acacia gum, pullulan, pustulan, scleroglucan, and mixtures thereof; and any combinations or mixtures thereof such different types of hydrocolloids.
  • non-gelling viscosity building additives selected from the group consisting of cellulose ethers, such as methyl cellulose, (non-modified) carboxymethylcellulose, hydroxyethylcellulose, hydroxyprop
  • additives that impart gel- forming characteristics to the modified CMC formulations include, without limitation, gel-forming additives selected from the group consisting of of gellan gum (high and low acyl forms), carrageenan (kappa and iota types), xanthan/locust bean gum, sodium alginate, curdlan, MHPC, pectin, and any combinations or mixtures thereof.
  • gel-forming additives selected from the group consisting of of gellan gum (high and low acyl forms), carrageenan (kappa and iota types), xanthan/locust bean gum, sodium alginate, curdlan, MHPC, pectin, and any combinations or mixtures thereof.
  • the optional polymeric additives listed above may be present therein in an amount of from 0.05 to 50% by weight of the entire film and/or capsule.
  • modified CMC particularly, whether alone or in combination with these other types of hydrocolloids and/or biogums, is the reduced viscosity exhibited thereby permits greater amounts of the modified CMC to be introduced within the film-forming solution than is customary. As discussed above, this permits a reduction in the amount of water needed for a proper film-forming composition to be produced and drastically reduces the time required for water evaporation. Furthermore, the film-forming solution can be easily and thoroughly mixed under relatively low energy levels such that a properly dispersed solution is accorded the film producer as well.
  • the modified CMC materials are present as long strands, rather than as coiled globules of CMC; thus, the avoidance of detrimental lumps within the film- forming solution is possible at the aforementioned low energy mixing levels.
  • the proper film-forming solutions thus will comprise from about 10 to about 50% of the modified CMC, from about 50 to about 90% by weight of water, and optionally, from 0 to about 12.5% by weight of a plasticizer.
  • the active ingredient is also incorporated within the film-forming solution and is thoroughly mixed therein as well for proper dispersion within the ultimate film.
  • Such an additive may be present in an amount of from about 0.001 to about 70% by weight of the entire composition.
  • the solution may also comprise other additional film-forming agents other than the hydrocolloids, cellulose ethers, and/or biogums listed above, such as, without limitation, polyvinyl pyrrolidone, polyvinyl alcohol, sodium alginate, polyethylene glycol, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, starch, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, , chitin, chitosan, levan, elsinan, collagen, gelatin, zein, gluten, soy protein isolate, whey protein isolate, casein, and mixtures thereof.
  • additional film-forming agents other than the hydrocolloids, cellulose ethers, and/or biogums listed above, such as, without limitation, polyvinyl pyrrolidone, polyvinyl alcohol, sodium alginate, polyethylene glycol, polyacrylic acid, methylmethacrylate copolymer
  • compositions of the present invention also comprise a safe and effective amount of a plasticizing agent to improve flexibility and reduce brittleness of the edible film composition.
  • Suitable plasticizing agents of the present invention include, but are not limited to, polyols (such as sorbitol; glycerin; polyethylene glycol; propylene glycol; acetylated monoglyceride; hydrogenated starch hydrolysates; corn syrups; and derivatives thereof; xylitol; glycerol monoesters with fatty acids; triacetin; diacetin; and monoacetin) and mixtures thereof.
  • the plasticizing agent of the present invention is glycerol.
  • compositions of the present invention may also comprise a safe and effective amount of an additive selected from the group consisting of a flavoring agent, an antimicrobial agent, an oral care and/or a pharmaceutical agent, a surfactant, a sweetener, a nutrient (such as a vitamin or mineral), and any combinations thereof.
  • Suitable flavoring agents include any well known food flavoring (of which there are a vast variety to choose from) including, without limitation, examples such as oil of wintergreen, oil of peppermint, oil of spearmint, clove bud oil, menthol, eucalyptol, lemon, orange, cinnamon, vanillin, and the like, and mixtures thereof.
  • the compositions may optionally comprise a vegetable oil.
  • the present invention may optionally comprise a safe and effective amount of an oral care active agent and/or a pharmaceutical active agent.
  • the oral care active agent suitable for use herein is selected from the group consisting of anticalculus agent, fluoride ion source, antimicrobial agents, dentinal desensitizing agents, anesthetic agents, antifungal agents, anti-inflammatory agents, selective H-2 antagonists, anticaries agents, nutrients, and mixtures thereof.
  • the oral care active agent preferably contains an active at a level where upon directed use, the benefit sought by the user is promoted without detriment to the oral surface to which it is applied.
  • oral conditions examples include, but, are not limited to, appearance and structural changes to teeth, whitening, stain removal, plaque removal, tartar removal, cavity prevention and treatment, inflamed and/or bleeding gums, mucosal wounds, lesions, ulcers, aphthous ulcers, cold sores, tooth abscesses, and the elimination of mouth malodor resulting from the conditions above and other causes such as microbial proliferation.
  • Suitable oral care actives include any material that is generally considered safe for use in the oral cavity and that provides changes to the overall appearance and/or health of the oral cavity.
  • the level of oral care substance in the compositions of the present invention is generally, unless specifically noted, from about 0.01% to about 50%, preferably from about 0.1% to aboixt 20%, more preferably from about 0.5% to about 10%, and even more preferably from about 1% to about 7%, by weight of the dry film composition.
  • the anticaries agent may be selected from the group consisting of xylitol, fluoride ion source, and mixtures thereof.
  • the fluoride ion source provides free fluoride ion during the use of the composition.
  • the oral care active agent is a fluoride ion source selected from the group consisting of sodium fluoride, stannous fluoride, indium fluoride, organic fluorides such as amine fluorides and sodium monofluorophosphate.
  • Sodium fluoride is the fluoride ion in another embodiment.
  • the anticalculus agent is selected from the group consisting of polyphosphates and salts thereof; diphosphonates and salts thereof; and mixtures thereof.
  • the anticalculus agent is selected from the group consisting of pyrophosphate, polyphosphate, and mixtures thereof.
  • the anticalculus agent is a polyphosphate, understood to mean a compound consisting of two or more phosphate molecules arranged primarily in a linear configuration, although some cyclic derivatives may be present. Counterions for these phosphates may be the alkali metal, alkaline earth metal, ammonium, C 2 -C 6 alkanolammonium and salt mixtures. Polyphosphates are generally employed as their wholly or partially neutralized water soluble alkali metal salts such as potassium, sodium, ammonium salts, and mixtures thereof.
  • the inorganic polyphosphate salts include alkali metal (e.g. sodium) tripolyphosphate, tetrapolyphosphate, dialkyl metal (e.g.
  • polyphosphates larger than tetrapolyphosphate usually occur as amorphous glassy materials.
  • the polyphosphates are those manufactured by FMC Corporation which are commercially known as Sodaphos, Hexaphos, and Glass H, and mixtures thereof.
  • Pyrophosphate salts may be utilized in a like manner to the polyphosphates noted above. Such would include alkali metal pyrophosphates, di-, tri-, and mono-potassium or sodium pyrophosphates, dialkali metal pyrophosphate salts, tetraalkali metal pyrophosphate salts, and mixtures thereof. More specifically, these may be, in non- limiting fashion, trisodium pyrophosphate, disodium dihydrogen pyrophosphate, dipotassium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, and mixtures thereof.
  • Optional agents to be used in place of or in combination with the pyrophosphate salt include such known materials as synthetic anionic polymers, including polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether (e.g., Gantrez), as described, for example, in U.S. Pat. No.
  • polyamino propoane sulfonic acid AMPS
  • zinc citrate trihydrate polyphosphates (e.g., tripolyphosphate; hexametaphosphate), diphosphonates (e.g., EHDP; AHP), polypeptides (such as polyaspartic and polyglutamic acids), and mixtures thereof.
  • polyphosphates e.g., tripolyphosphate; hexametaphosphate
  • diphosphonates e.g., EHDP; AHP
  • polypeptides such as polyaspartic and polyglutamic acids
  • Antimicrobial antiplaque agents may also by optionally present in the present compositions.
  • Such agents may include, but are not limited to, triclosan, 5-chloro-2-(2,4- dichlorophenoxy)-phenol, chlorhexidine, alexidine, hexetidine, sanguinarine, benzalkonium chloride, salicylanilide, domiphen bromide, cetylpyridinium chloride (CPC), tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC), octenidine, delmopinol, octapinol, and other piperidino derivatives; effective antimicrobial amounts of essential oils and combinations thereof for example citral, geranial, and combinations of menthol, eucalyptol, thymol and methyl salicylate; antimicrobial metals and salts thereof for example those providing zinc ions, stannous ions, copper
  • Anti-inflammatory agents may also be present in the oral compositions of the present invention.
  • Such agents may include, but are not limited to, non-steroidal antiinflammatory agents such as aspirin, ketorolac, flurbiprofen sodium, ibuprofen, acetaminophen, diflunisal, fenoprofen calcium, naproxen, indomethacin, ketoprofen, tolmetin sodium, piroxicam and meclofenamic acid, COX-2 inhibitors such as valdecoxib, celecoxib and rofecoxib, and mixtures thereof.
  • the present invention may also include a safe and effective amount of a selective H-2 antagonist such as, without limitation, cimetidine, etintidine, ranitidine, tiotidine, lupitidine, donetidine, famotidine, roxatidine, pifatidine, lamtidine, zaltidine, nizatidine, mifentidine, ramixotidine, loxtidine, bisfentidine, sufotidine, ebrotidine, and impromidine.
  • a selective H-2 antagonist such as, without limitation, cimetidine, etintidine, ranitidine, tiotidine, lupitidine, donetidine, famotidine, roxatidine, pifatidine, lamtidine, zaltidine, nizatidine, mifentidine, ramixotidine, loxtidine, bisfentidine, sufotidine, ebrotidine, and impromidine.
  • Nutrients include minerals, vitamins, oral nutritional supplements, enteral nutritional supplements, and mixtures thereof.
  • Minerals that can be included with the compositions of the present invention include calcium, phosphorus, fluoride, zinc, manganese, potassium and mixtures thereof.
  • Vitamins can be included with minerals or used separately.
  • Vitamins include Vitamins C and D, thiamine, riboflavin, calcium pantothenate, niacin, folic acid, nicotinamide, pyridoxine, cyanocobalamin, para- aminobenzoic acid, bioflavonoids, and mixtures thereof.
  • Oral nutritional supplements include amino acids, lipotropics, fish oil, and mixtures thereof.
  • Amino acids include, but, are not limited to L-Tryptophan, L-Lysine, Methionine, Threonine, Levocarnitine or L- carnitine and mixtures thereof.
  • Lipotropics include, but, are not limited to choline, inositol, betaine, linoleic acid, linolenic acid, and mixtures thereof.
  • Fish oil contains large amounts of Omega- 3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid.
  • Antioxidants that may be included in the oral care composition or substance of the present invention include, but are not limited to Vitamin E, ascorbic acid, Uric acid, carotenoids, Vitamin A, flavonoids and polyphenols, herbal antioxidants, melatonin, aminoindoles, lipoic acids and mixtures thereof.
  • Enteral nutritional supplements include, but, are not limited to protein products, glucose polymers, corn oil, safflower oil, and medium chain triglycerides.
  • Anti-pain or desensitizing agents and anesthetic agents can also be present in the oral care compositions or substances of the present invention.
  • Such agents may include, but are not limited to, strontium chloride, potassium nitrate, natural herbs such as gall nut, Asarum, Cubebin, Galanga, Scutellaria, Liangmianzhen, Baizhi, etc.
  • Anesthetic agents include lidocaine, benzocaine, etc.
  • the pharmaceutical active agent suitable for use herein is selected from the group consisting of sedatives, hypnotics, antibiotics, antitussives, antihistamines, non-sedating antihistamines, decongestants, expectorants, mucolytics, antidiarrheals, analgesics- antipyretics, proton pump inhibitors, general nonselective CNS stimulants, drugs that selectively modify CNS function, antiparkinsonism drugs, narcotic-analgesics, psychopharmacological drugs, laxatives, dimenhydrinates, and mixtures thereof.
  • Preferred pharmaceutical actives suitable for use as an active ingredient herein include antitussives, antihistamines, non-sedating antihistamines, decongestants, expectorants, mucolytics, analgesics-antipyretics, anti-inflammatory agents, antidiarrheals, and mixtures thereof.
  • Suitable surfactants are those which are reasonably stable and include nonionic, anionic, amphoteric, cationic, zwitterionic, synthetic detergents, and mixtures thereof.
  • compositions may optionally comprise sweetening agents including sucralose, sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts, thaumatin, aspartame, D-tryptophan, dihydrochalcones, acesulfame and cyclamate salts, especially sodium cyclamate and sodium saccharin, and mixtures thereof.
  • sweetening agents including sucralose, sucrose, glucose, saccharin, dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol, saccharin salts, thaumatin, aspartame, D-tryptophan, dihydrochalcones, acesulfame and cyclamate salts, especially sodium cyclamate and sodium saccharin
  • Coolants salivating agents, warming agents, coloring agents, and numbing agents can be used as optional ingredients in compositions of the present invention as well.
  • the film compositions utilized in accordance with the invention are formed by processes conventional in the arts, e.g. the paper-making and/or film making industries. Generally the separate components of the film are blended in a mixing tank until a homogeneous mixture is achieved. Thereafter, the films can be cast to an acceptable thickness, on an appropriate substrate. Examples of such substrates include Mylar, continuous moving stainless steel belt (eventually entering a dryer section), release paper and the like. The webs are then dried, e.g. in a forced-air oven. The temperature of the drying air and length of drying time depend on the nature of the solvent utilized as is recognized in the art.
  • the films contemplated herein are dried at a temperature between about 25°C (i.e., ambient temperature) and 14O 0 C (with a lower temperature preferred to reduce costs), for a duration of about 20 minutes to about 60 minutes, in another embodiment from about 30 to about 40 minutes. Drying of these films should be carried out in a way that moisture gradients are minimized in the film. Such gradients come from rapid drying and lead to curling and lack of dimensional stability. When dried properly, the films will have a final water activity of 0.5 (+/- 0.25) so that they do not either take up or lose significant amount of water when exposed to normal ambient conditions. The moisture content will vary depending upon the composition of the film, it's water activity rather than water content that is the parameter to be controlled.
  • Films with a low water content may be dried in as little as 30 minutes at 4O 0 C.
  • the optimal temperature of the film during drying is usually lower than 65C°. Higher temperatures can be used, especially if the film is dried simultaneously from the top and bottom. This can be accomplished by using a heated metal belt of the bottom and indirect intra-red heating from above. Microwave techniques and other novel drying technologies can also be used successfully.
  • the film After exiting from the dryer section of the casting belt, the film can be wound on a spool for storage under sanitary conditions. The film can be slit into two inch rolls for further cutting to form 1 inch by 2 inch (or other desired dimensions) and then stacked and subsequently individually packaged.
  • Extrusion is also a possible method of film manufacture.
  • the mechanical particulars of the extrusion process e.g. the particular equipment utilized, the extruding force, the shape and temperature of the orifice are considered to be within the skill of the art and can be varied in a known manner to achieve the physical characteristics of the films described herein.
  • the films herein are generally between about 1 and about 10 mils (about 0.025 mm to about 0.25 mm), in another embodiment are from about 1.2 to about 2.5 mils (about 0.03 mm to about 0.064 mm) thick.
  • a convenient width for such films is about 0.75 to about 1 inch, although the width of the film is not particularly critical to the practice of the invention.
  • the film can be produced in any length. However, in view of the fact that the novel dosage forms produced in accordance with the invention are suited to high speed manufacture, the films should be prepared in large quantity, e.g. 15,000 feet or more which can be stored, e.g. on cores or spools.
  • the capsules made therefrom may be produced through typical capsule- making procedures utilizing the same basic solutions as the film-making methods.
  • the required modified CMC may be applied in hard (two-piece) and/or soft (one-piece) capsules.
  • hard capsules connotes that such materials must retain their shape from the time of manufacture through being filled and ultimately until they are ingested for use.
  • Soft capsules exhibit a soft shell only at the moment they are formed and filled.
  • One-piece capsules are generally sold as formulated products whereas hard capsules are generally manufactured empty and filled at a later time.
  • Gelatin has traditionally been the material of choice within the capsule industry. Gelatin exhibits a number of properties that make such a material a proper candidate for capsule manufacture including good film forming properties (strength and flexibility, primarily), good solubility in biological fluids at typical body temperature, low viscosity at 50°C at high solids concentrations, and a gel state at low temperatures. Likewise, methylhydropropyl cellulose has recently found favor within the capsule industry for the same basic reasons.
  • Soft capsules containing gelatin are made by passing two flexible sheets of gelled plasticized gelatin solution between a pair of rotating cylinders.
  • the gelatin sheets are passed over and are sealed together by mechanical pressure and heat.
  • the films are half sealed before the filling process starts.
  • the cylinders have cavities in their surfaces and the gelatin sheet is forced into their shape by the pressure of the fill material as it is pumped between the cylinders. Subsequent to such a step, the resultant capsules are then dried.
  • the gelatin solution requires a significant quantity of plasticizer to form the necessary flexible sheets for introduction within the capsule- production process.
  • Hard capsules containing gelatin are made by dipping 'cold' stainless steel mold pins at a temperature of 22 0 C in a 30-40% gelatin solution present at 50-60 0 C.
  • the pins will pick up the target gelatin due to gelling while the excess runs off.
  • the viscosity of the gelatin solution determines the quantity picked up by the molds during capsule formation.
  • the pin bars are then rotated in order to facilitate spread of the gelatin as uniformly as possible over the subject mold surface.
  • the last step is a drying step.
  • Hard capsules containing MHPC are made on smaller mould pins to enable capsules with thinner walls to be made. This is required to give them sufficient strength to be filled and retain the same external dimensions as a gelatin capsule.
  • Two methods are used. One is using thermal gelation of HPMC. The other is using a gelling agent (e.g. carrageenan or gellan gum) and a gelation promoter.
  • a gelling agent e.g. carrageenan or gellan gum
  • typically a gelling agent should be added. In case of soft capsules this is required to form a wet sheet together with the modified CMC, that will be mechanically deformable.
  • the gelling agent is needed to get sufficient surface gelling at the mold pins thereby picking up sufficient modified CMC material to form the required (uniform) capsule dimension.
  • the gelling agent should not compromise the modified CMC film- forming properties, nor cause too great a viscosity increase within the solution.
  • the final modified CMC-containing capsule films should have a suitable strength. Furthermore, the capsules should be readily soluble in biological fluids at body temperature.
  • modified CMC can be used to form capsules
  • the low acyl version of this product has a setting temperature of approximately 4O 0 C (within the same range as gelatin).
  • the gellan gum is much higher in gel strength than commonly used gelatins and so only a low concentration can be used. Higher levels result in gellan gum-alone solutions that are too thick and viscous to be processed.
  • Using the modified CMC in conjunction with gellan gum allows the CMC to function as a film former and the gellan gum to thermally set and form the capsule in a manner similar to the gelatin.
  • Other gelling hydrocolloids can function in the same way with the only requirement being that they have an easily triggered gel mechanism.
  • hydrocolloids are familiar with the thermal gelation of xanthan and locust bean gums or with the calcium gelation mechanism of sodium alginate, and such possible alternatives are thus non-limiting examples of potential gelling hydrocolloids for this purpose.
  • a wide range of gelling hydrocolloids can be used in conjunction with the modified CMC when it is realized that the film forming properties of the modified CMC can be effectively paired with the gel forming properties of the second hydrocolloid system.
  • the pH was then adjusted again to 5.8 using the same phosphoric acid solution.
  • the reaction was performed at 50 0 C while stirring for 16 hours and was eventually stopped by inactivating the enzyme in an autoclave at 121 0 C for one hour.
  • the resultant modified CMC solutions were then dried by either freeze-drying or spray drying.
  • Methocel® E5 sample exhibits excellent dissolution rates
  • films prepared with such materials exhibit excessive adhesion characteristics and thus, in actuality, such films would exhibit much slower dissolution in practice than modified CMC films.
  • modified CMC materials exhibited much better low adhesion properties and thus in practice provided much better quick dissolution capabilities than such hydroxypropylmethylcellulose materials.
  • the modified CMC types exhibited excellent solubility times and a high concentration of the modified CMC can be prepared as compared with the other hydrocolloids tested.
  • the modified CMC was weighed out and dissolved into tap water.
  • glycerol was weighed out and added to the dissolved modified CMC solution, (preferred; could be premix, too) Air bubbles within the resultant solution were removed by centrifugation or by vacuum. That solution was then cast using a draw-down bar on a plastic sheet into thin even layers. The layers were then dried at room temperature to form films exhibiting final thicknesses of between 20 and 500 ⁇ m.
  • the remainder of the solution utilized to form the films was tap water (thus, if 50% was CMC, and the plasticizer: CMC ratio is 1:10, then 5% of the solution was plasticizer, and 45% was then tap water, for example). Also, if no plasticizer was added, the term "None" is used and thus the remainder of the film- producing solution was tap water alone. Additionally, film example 18 included 6% (ratio CMC: modified CMC - 1: 6) of non-modified CMC (CEKOL® 30) in combination with the noted modified type, and thus the amount of tap water was adjusted accordingly. Furthermore, film example 23 included 1% of pectin GENU® X-934-04) in combination with the noted modified type, with 22.8 g of water. Lastly, the notation of G after the plasticizer: CMC ratio denotes glycerol as the plasticizer, whereas the notation of S denotes the utilization of sorbitol.
  • Film Examples 1-4 from Table 3 were tested for flexibility. The films produced thereby were bent backward length- wise (hairpin bending) to investigate the breaking point thereof. If the film exhibiting cracking when bent in such a fashion, it was considered a failure. Film Example numbers 2-4 exhibited no cracking. Film Example 1 exhibited greater brittleness. Film Examples 3 and 4 exhibited greater flexibility overall, but due to the high plasticizer content the films are tacky. Thus, in terms of molecular weight, at least, the higher the molecular weight, coupled with lower amounts of plasticizer provided excellent flexibility results without tackiness.
  • the modified CMC films measured provide excellent dissolution in comparison with all of these standard types.
  • Certain properties such as tensile strength, elongation, toughness, and elastic modulus were measured for resultant films as well to indicate the viability of such films as potential commercial products. Such measurements were taken through standard techniques. A texture analyzer from Stable Micro Systems equipped with tensile grips was used to determine the mechanical properties of the films at 50% RH. To determine the influence of molecular weight, Film Example numbers 20 and 21 were analysed for such mechanical properties. Film Example 20 has a higher molecular weight than Film Example 21 (MW of 50500 versus 21200). The average of 6 measurements was calculated and shown in table 6.
  • the toughness of Film 20 is almost 3 times as high as Film 21, while the elongation of film 20 is only 1.3% bigger than the elongation for film 21.
  • the E-modulus and the tensile strength of Film 20 is about twice as high as for Film 21.
  • Modified CMC has a high clarity and low haziness. This is already visible when the solutions are prepared. Modified CMC was compared to other hydrocolloids used for making films. The clarity and haziness were measured with a BYK-Gardner haze-gard plus of 10 % solutions of hydrocolloids. If the DS of the modified CMC is not too low the clarity is high and the haziness is low. Other hydrocolloids may have a high clarity, but they can have a high haziness like the pectin samples. The results are shown in the table below. Each sample solution mentioned below was measured at the same thickness (2 mm). TABLE 7
  • the modified CMC films having not too low DS levels, exhibited excellent measurements in both properties as opposed to the comparatives (MHPC is an exception).
  • plasticizers than glycerol can be used to prepare films from modified CMC.
  • Film Example numbers 17 and 22 prepared with sorbitol as a plasticizer resulted both in flexible and not tacky films tested in humidity range from 20% up to 70% relative humidity (RH).
  • Such a film was produced in accordance with the composition of the preceding table through the following process: Modified CMC was added to the water and glycerin while mixing at 1200 rpm with a propeller mixer. After addition of the modified CMC the mixing was continued at high speed. After ⁇ 15 minutes the sucralose was added. Addition of citric and malic acid was started when the sucralose had fully dispersed. After all the acid was added first the flavor was added and then the color. When the sample was uniform in appearance, the mixer was removed and the sample was deaerated using either vacuum or centrifugation.
  • Such a film was produced in accordance with the composition of the preceding table and in accordance with the following method: Modified CMC was added to the water and glycerin while mixing at 1200 rpm with a propeller mixer. After addition of the modified CMC the mixing was continued at high speed. After -15 minutes the remaining ingredients were added and when the sample was uniform in appearance the mixer was removed and the sample was deaerated using either vacuum or centrifugation. A portion of the solution was poured on to the plastic sheet and a draw down bar was used to draw the solution down into a thin layer of a thickness of about 0.01 inch. The films were allowed to stand undisturbed until thoroughly dried. Final film thickness was 0.002 inch. The resultant films exhibited excellent dissolution times (on par, again, with those presented above) and surfactant delivery capability.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Polymers & Plastics (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Inorganic Chemistry (AREA)
  • Biotechnology (AREA)
  • Materials Engineering (AREA)
  • Genetics & Genomics (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • General Preparation And Processing Of Foods (AREA)
  • Jellies, Jams, And Syrups (AREA)
  • Enzymes And Modification Thereof (AREA)
EP06827160A 2005-11-01 2006-10-31 Filme und kapseln aus modifizierten carboxy-methylcellulose-materialien und herstellungsverfahren Withdrawn EP1954250A2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US11/264,260 US20070098779A1 (en) 2005-11-01 2005-11-01 Films and capsules made from modified carboxymethylcellulose materials
US11/264,262 US20070166371A1 (en) 2005-11-01 2005-11-01 Methods of producing films and capsules made from modified carboxymethylcellulose materials
PCT/US2006/042452 WO2007053608A2 (en) 2005-11-01 2006-10-31 Films and capsules made from modified carboxymethycellulose materials and methods of making same

Publications (1)

Publication Number Publication Date
EP1954250A2 true EP1954250A2 (de) 2008-08-13

Family

ID=38006458

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06827160A Withdrawn EP1954250A2 (de) 2005-11-01 2006-10-31 Filme und kapseln aus modifizierten carboxy-methylcellulose-materialien und herstellungsverfahren

Country Status (11)

Country Link
EP (1) EP1954250A2 (de)
JP (1) JP5364377B2 (de)
KR (2) KR20080106160A (de)
CN (2) CN103772520B (de)
AP (2) AP2878A (de)
AU (2) AU2006308904B9 (de)
CA (1) CA2628207A1 (de)
EA (2) EA015170B1 (de)
MX (3) MX2008005643A (de)
WO (2) WO2007053612A2 (de)
ZA (1) ZA200804213B (de)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110027838A1 (en) 2009-07-31 2011-02-03 Harding Nancy E Sphingomonas Strains Producing Greatly Increased Yield Of PHB-Deficient Sphingan (Diutan)
DK3095447T3 (da) 2006-02-03 2022-01-31 Opko Renal Llc Behandling af vitamin d-insufficiens og -mangel med 25-hydroxyvitamin d2 og 25-hydroxyvitamin d3
CN101553261B (zh) 2006-06-15 2014-01-29 生物高聚物工程公司Dba生物治疗公司 葡聚糖的制备
PL2679228T3 (pl) 2006-06-21 2018-07-31 Opko Ireland Global Holdings, Ltd. Terapia z użyciem środka do uzupełniania witaminy D i środka do zastępowania hormonami witaminy D
JP5501956B2 (ja) 2007-04-25 2014-05-28 シトクロマ インコーポレイテッド ビタミンｄ化合物およびワックス状担体を含有する制御放出性経口組成物
EP3335712A1 (de) 2007-04-25 2018-06-20 Opko Renal, LLC Verfahren zur sicheren und effektiven behandlung und vorbeugung von sekundärem hyperparathyroidismus bei chronischer nierenerkrankung
CN101668532B (zh) 2007-04-25 2014-08-20 赛特克罗公司 治疗维生素d不足和缺乏、继发性甲状旁腺功能亢进症和维生素d-响应疾病的组合物及其相应的制药用途
US20080274182A1 (en) * 2007-05-03 2008-11-06 Regina Helena Alida Boekema Tablet coatings made from modified carboxymethylcellulose materials
US20100234329A1 (en) * 2007-10-31 2010-09-16 Belanger Eve Ingestible film composition
CN102046812A (zh) 2008-04-02 2011-05-04 赛特克罗公司 用于维生素d缺乏症和相关障碍的方法、组合物、用途和试剂盒
LT2552484T (lt) 2010-03-29 2020-04-27 Opko Ireland Global Holdings, Ltd. Būdai ir kompozicijos, skirti paratiroidų lygiams sumažinti
US9296939B2 (en) 2010-05-05 2016-03-29 Halliburton Energy Services, Inc. Compositions for modifying rheological properties of cement systems
US9296943B2 (en) 2012-05-22 2016-03-29 Schlumberger Technology Corporation Subterranean treatment fluid composition and method of treatment
KR20140072716A (ko) * 2012-12-05 2014-06-13 삼성정밀화학 주식회사 헤이즈가 개선된 필름
KR101847947B1 (ko) 2013-03-15 2018-05-28 옵코 아이피 홀딩스 Ⅱ 인코포레이티드 안정화되고 변형된 비타민 ｄ 방출 제형
KR102161001B1 (ko) * 2013-12-31 2020-09-29 롯데정밀화학 주식회사 경질 캡슐용 수성 조성물 및 이를 사용하여 제조된 경질 캡슐
KR102199595B1 (ko) * 2013-12-31 2021-01-07 롯데정밀화학 주식회사 경질 캡슐용 수성 조성물 및 이를 사용하여 제조된 경질 캡슐
KR102199596B1 (ko) * 2013-12-31 2021-01-07 롯데정밀화학 주식회사 경질 캡슐용 수성 조성물 및 이를 사용하여 제조된 경질 캡슐
EP3166616B1 (de) 2014-07-10 2021-04-07 Biothera, Inc. Beta-glucan in kombination mit antikrebsmittel mit beeinflussung der tumormikroumgebung
JP2017523220A (ja) 2014-08-07 2017-08-17 オプコ アイルランド グローバル ホールディングス リミテッド ２５−ヒドロキシビタミンｄを用いる補助的療法
CN107106593B (zh) 2014-11-06 2021-05-07 百奥赛诺公司 影响肿瘤微环境的β-葡聚糖方法与组合物
BR112018069727A2 (pt) 2016-03-28 2019-02-05 Opko Ireland Global Holdings Ltd métodos de tratamento com vitamina d
US11815435B2 (en) 2017-02-24 2023-11-14 Hibercell, Inc. Beta glucan immunopharmacodynamics
CN106977618B (zh) * 2017-04-13 2022-07-01 张星昊 一种从定优胶发酵液中提取定优胶的方法
KR102065953B1 (ko) * 2018-02-07 2020-02-11 충남대학교산학협력단 카복시메틸나노셀룰로오스 복합필름 제조용 조성물, 필름 및 이의 제조방법
CA3105187A1 (en) 2018-06-28 2020-01-02 Arx, Llc Dispensing method for producing dissolvable unit dose film constructs
CN111807785B (zh) * 2020-07-17 2022-02-15 中铁建工集团有限公司 一种大体积自密实混凝土及其制备方法
CN112680435B (zh) * 2021-01-25 2022-03-25 中国石油大学(华东) 一种鞘氨醇胶裂解酶及酶解鞘氨醇胶的制备方法

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6696561B1 (en) * 1909-07-09 2004-02-24 Basf Aktiengesellschaft Corynebacterium glutamicum genes encoding proteins involved in membrane synthesis and membrane transport
IL79165A0 (en) * 1985-06-28 1986-09-30 Merck & Co Inc Heteropolysaccharide s-657 and its preparation
US5175278A (en) * 1985-06-28 1992-12-29 Merck & Co., Inc. Heteropolysaccharide S-657
US5366755A (en) * 1989-02-10 1994-11-22 Maritta Timonen Foodstuffs containing novel degraded cellulose derivatives
US5550189A (en) * 1992-04-17 1996-08-27 Kimberly-Clark Corporation Modified polysaccharides having improved absorbent properties and process for the preparation thereof
US5985623A (en) * 1995-01-24 1999-11-16 Shin-Etsu Bio, Inc. DNA segments and methods for increasing polysaccharide production
JPH09252775A (ja) * 1995-01-24 1997-09-30 Shin Etsu Chem Co Ltd Ｄｎａセグメント及び多糖類の高生産方法
ATE190971T1 (de) * 1995-12-15 2000-04-15 Monsanto Co Verfahren zur verbesserten rheologischen steuerung bei zementsystemen
US6103671A (en) * 1997-11-20 2000-08-15 Texas United Chemical Company Llc. Glycol solution drilling system
GB9924634D0 (en) * 1999-10-19 1999-12-22 Univ St Andrews Enzyme
US6627785B1 (en) * 2000-02-29 2003-09-30 Virginia Commwealth University Wound dressings with protease-lowering activity
US7439044B2 (en) * 2003-03-21 2008-10-21 Cp Kelco U.S., Inc. High viscosity xanthan polymer preparations
US7052540B2 (en) * 2004-03-11 2006-05-30 Eastman Chemical Company Aqueous dispersions of carboxylated cellulose esters, and methods of making them
US20060041961A1 (en) * 2004-03-25 2006-02-23 Abad Mark S Genes and uses for pant improvement
US7888333B2 (en) * 2005-02-04 2011-02-15 Cp Kelco U.S., Inc. Targeted gene deletions for polysaccharide slime formers

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2007053608A2 *

Also Published As

Publication number Publication date
AP2008004489A0 (en) 2008-06-30
MX2008005643A (es) 2008-12-09
MX2008005874A (es) 2008-11-27
WO2007053608A2 (en) 2007-05-10
ZA200804213B (en) 2022-03-30
AU2006308904B9 (en) 2013-01-10
AP2008004491A0 (en) 2008-06-30
KR20080106160A (ko) 2008-12-04
AP2878A (en) 2014-03-31
MX348439B (es) 2017-06-13
WO2007053608A3 (en) 2009-01-22
CN103772520B (zh) 2018-04-10
EA200801224A1 (ru) 2009-04-28
EA200801223A1 (ru) 2009-06-30
AU2006308904A1 (en) 2007-05-10
KR101372110B1 (ko) 2014-03-14
CN103772520A (zh) 2014-05-07
CN101558165A (zh) 2009-10-14
JP5364377B2 (ja) 2013-12-11
CA2628207A1 (en) 2007-05-10
JP2009515512A (ja) 2009-04-16
AU2006308904B2 (en) 2012-12-06
WO2007053612A2 (en) 2007-05-10
WO2007053612A3 (en) 2007-12-06
AU2006310988A1 (en) 2007-05-10
KR20090016655A (ko) 2009-02-17
CN101558165B (zh) 2013-07-03
EA015170B1 (ru) 2011-06-30

Similar Documents

Publication Publication Date Title
WO2007053608A2 (en) Films and capsules made from modified carboxymethycellulose materials and methods of making same
US20070098779A1 (en) Films and capsules made from modified carboxymethylcellulose materials
RU2266104C2 (ru) Пленка, освежающая дыхание
CN1297601C (zh) 改性淀粉成膜组合物及其用途
CA2522295C (en) Homogeneous, thermoreversible gel film containing kappa-2 carrageenan and soft capsules made therefrom
US8840935B2 (en) Orally administrable films and preparation thereof
CA2520383C (en) Rapidly dissolving edible film compositions with improved film strength and stability
JP2003505565A (ja) プルラン膜組成物
AU2002313766A1 (en) Breath freshening film
US20080274182A1 (en) Tablet coatings made from modified carboxymethylcellulose materials
AU2020264030B2 (en) Tooth whitening film, process of manufacture thereof and a method of using such a film
TW200848094A (en) Fast disintegration monolayer film for buccal administration of active substances
US20070166371A1 (en) Methods of producing films and capsules made from modified carboxymethylcellulose materials
US20240050198A1 (en) Dental kit comprising a dental aligner or a mouth tray and dissolvable films
JP7380545B2 (ja) 皮膜組成物及び該皮膜組成物を用いたカプセル剤
WO2023250297A1 (en) Film forming delayed/enteric formulations for hard shell capsules, films and coatings

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20080602

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA HR MK RS

RIC1 Information provided on ipc code assigned before grant

Ipc: H05K 1/09 20060101AFI20090218BHEP

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: CP KELCO U.S., INC.

RIN1 Information on inventor provided before grant (corrected)

Inventor name: CLARK, ROSS

Inventor name: HOPMAN, ANJA MARIA CHRISTINA PETRONELLA

Inventor name: VAESSEN-VAN HOVEN, HENRICE WILHELMINA CORNELIA

Inventor name: HANZEN, ANDRIES

R17D Deferred search report published (corrected)

Effective date: 20090122

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20100601