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WO2009070978A1 - Libération rapide dans la cavité buccale des produits de santé et procédé de préparation associé - Google Patents

Libération rapide dans la cavité buccale des produits de santé et procédé de préparation associé Download PDF

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Publication number
WO2009070978A1
WO2009070978A1 PCT/CN2008/001889 CN2008001889W WO2009070978A1 WO 2009070978 A1 WO2009070978 A1 WO 2009070978A1 CN 2008001889 W CN2008001889 W CN 2008001889W WO 2009070978 A1 WO2009070978 A1 WO 2009070978A1
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Prior art keywords
oil
preparation
dispersant
oily
soluble
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PCT/CN2008/001889
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English (en)
Chinese (zh)
Inventor
Yu He
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Individual
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Individual
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    • 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

Definitions

  • the invention withdraws a vitamin oral release preparation and a preparation method thereof, and belongs to the technical field of a medullary preparation.
  • the health care products referred to in this patent may be cage foods, functional foods, health products, new resource foods, and food forms.
  • Oral immediate release dosage form as a new type of preparation is more popular with consumers.
  • the tablet does not require water to be taken, and the saliva dissolves rapidly in the mouth, which provides convenience for patients who have poor swallowing function and inconvenient water intake, and has broad market prospects.
  • These dosage forms can disintegrate and dissolve in the legs, have a quick onset, improve the absorption and bioavailability of the functional ingredients, and reduce the irritation to the esophagus and gastrointestinal tract.
  • the oral immediate release preparations include two kinds of oral instant preparations and oral rapid disintegration preparations, all of which adopt the rapid absorption of oral water as the quick release method of the preparation.
  • the object of the present invention is: ⁇ 3 ⁇ 4 for a health care product oral immediate release preparation utilizing a hot melt mechanism and its manufacture: a method for modifying a conventional medullary preparation method by a broad spectrum adaptive preparation platform technology
  • a very ideal oral immediate release dispersion system (Fig. 1).
  • the water-soluble dispersant and the main ingredient are uniformly distributed in the oil's dispersant, which can improve the efficacy of health care products under the premise of reaching the taste of the town.
  • the rate of dispersion of the ingredients in the mouth and the rate of absorption of the active ingredient are uniformly distributed in the oil's dispersant, which can improve the efficacy of health care products under the premise of reaching the taste of the town.
  • the rate of dispersion of the ingredients in the mouth and the rate of absorption of the active ingredient are uniformly distributed in the oil's dispersant, which can improve the efficacy of health care products under the premise of reaching the taste of the town.
  • the basic raw material of the preparation is a main material and an auxiliary material, and the main ingredient is the raw material of the product; the auxiliary material is an oily dispersant; the weight percentage of the main material is 9% ⁇ The percentage by weight of the auxiliary material is 20% ⁇ 99. 9%.
  • the auxiliary material is an oily dispersing agent and a water-soluble dispersing agent, a flavoring agent and an emulsifier, wherein the water-soluble dispersing agent, the flavoring agent and the emulsifier account for not more than 85% by weight of the auxiliary material.
  • a functional filler may be added to the main material; the functional filler accounts for not more than 98% by weight of the main material; the functional filler includes: high-quality polymers of natural origin, sugars, cellulose and Derivatives, starches and derivatives thereof, cyclodextrins and derivatives thereof, polymers, inorganic salts, pH adjusters.
  • the oily dispersing agent comprises artificial oils or natural oils, which are worms or combinations, and can be classified into two types: vegetable oils and animal fats, and the oily dispersing agent should be added in an amount of not less than the oil content of the finished product. 15%, it is necessary to satisfy the formulation in the slurry state, the oil is the continuous phase.
  • the oily dispersing agent can also be finely soluble in a grease surfactant;
  • the oil-soluble surfactant is lecithin, polyethylene glycol, polyether, Span, Tween, sucrose fatty acid ester, mono-fatty acid glyceride , di-fatty acid glycerides, tri-fatty acid glycerides, polyglycerides, «alkanol mono-fatty acid esters, p-polyglycol fatty acid esters, fat derivatives, stearyl alcohol, cetyl alcohol, semi-synthetic fatty acids Ester, propylene glycol fatty acid ester, organic acid monoglyceride, monool fatty acid ester, which are used singly or in combination,
  • the oily oil used in the oil dispersant has a melting point of i ⁇ 20 ⁇ 70 °C.
  • the water-soluble dispersing agent in the auxiliary material is a sugar; the sugar includes glucose, candied fruit, sucrose, brown sugar, brown sugar, white sugar, occupation, starch sugar, maltose, verbasnic sugar, lactose, dextrin, erythritol, wood Sugar alcohol, fructitol, mannitol, sorbitol, lactitol, galactitol, maltitol, isomalt, isomalt, palitol, isomalt, oligo-isomalt, arabinose Alcohol, oligo-isomaltose, oligosaccharide, galacto-oligosaccharide, oligomannose, oligofructose, oligo-maltose, oligo-oligo-oligosaccharide, oligo-fructose, oligo-milk, low-poly cane Fructose, branched oligofructose,
  • the water-soluble ingredient can be used in a single shed or in combination.
  • the water-soluble dispersing agent in the auxiliary material can also be made of water-soluble honey, bee king, Amino acids, a-base acid salts, common salt salts, peptides, proteins, which can be singly or combined.
  • the manufacturing method of the oral release preparation of the health care product, the 3 ⁇ 43 ⁇ 4 process flow is as follows:
  • the solid particles are refined and uniformly dispersed in the oily dispersant to become a mass, the fineness of the particles is 95% of the weight of the preparation below 200, and the solid particles are dispersed in the oily dispersant by stirring.
  • the weight percentage of the amount of the oily dispersant should be equal to not less than 15% of the oil content in the finished product, and the flow rate of the bucket can be flowed under the cattle at 22 ⁇ 60 °C; according to the stage of the addition of the oily dispersant, the solid particles are refined.
  • the method is dry pulverization, semi-dry pulverization or wet pulverization;
  • the finished product is prepared by a cooling molding method or a powder molding method.
  • the solid particle refining may be carried out by a grinding method, which is a roll grinding method, a refining method, a ball milling method, a vibration grinding method or a mixing method.
  • the dry pulverization is refined under the low oil content of the material, and the pulverized state of the material is a dry powder having fluidity; specifically, all the oil-insoluble solid materials " ⁇ main ingredient 3 ⁇ 4 soluble dispersant are mixed, added or
  • the semi-dry pulverization is carried out under the condition that the oil content of the material is moderate, and the pulverized state of the material is a wet semi-dry state; specifically, all the oil-insoluble solid materials are added.
  • the wet pulverization is refined under the condition that the material has high oil content, and the material is pulverized in liquid state. Or paste state; specifically, all the oil-insoluble solid materials ⁇ 3 ⁇ 4 material 3 ⁇ 4: soluble dispersant mixed, with or without some or all of the oily dispersant, pulverized to the final fineness, after the fineness is reached, then the remaining
  • the sleeve dispersing agent is uniformly stirred and discharged, and the oily dispersing agent can be added in stages.
  • the oily dispersant of the present invention is an important component of the present invention, and its function is to uniformly disperse a solid component in an oily dispersant.
  • the oily dispersant has a melting point and a human being, that is, 3 ⁇ 43 ⁇ 4 is liquid when it is human, and it is solid when it is lower than human (normal temperature).
  • This hot melt oral release is completely different from the traditional aqueous immediate release mechanism and has not been reported.
  • the oral cavity causes the oily dispersant to be melted by heat. With the gradual purification of the oily dispersant, the solid component containing the health product is distributed in the mouth with the liquid oily dispersant in the form of a dip in order to complete The initial release process of the ingredients. ,
  • All the solid components in the component of the present invention are uniformly dispersed in the oily dispersant, in a slurry state at a temperature exceeding normal temperature, in a solid state at a normal temperature, and the solid component is encapsulated in an oily dispersant in a solid form. .
  • the slurry, cold state is solid and reversible.
  • the present invention utilizes such a reversible property, and can maintain the dispersion stability of a solid component at a normal temperature storage (preventing agglomeration or sedimentation of a solid component which is liable to occur in a micro- ⁇ state, precipitation of oil and fat) and stability of the component itself (hygroscopicity, Oxidation, etc.).
  • the preparation is a solid pre-emulsified dispersion system. After receiving oral heat and absorbing a small amount of saliva, it enters the body with a water-in-oil emulsified liquid. When the stomach liquid phase is converted into an oil-in-water dispersion, the functional ingredients are quickly dispersed. Since the surface is adsorbed with an emulsifier and an oil-soluble dispersant, no secondary agglomeration occurs.
  • the weight percentage of the main material is 0. 1% ⁇
  • the weight of the main material is 0. 1% ⁇ 9% ⁇ 80%
  • the weight percentage of the auxiliary material is 20% ⁇ 99. 9%.
  • the basic raw material of the preparation consists of two parts, a main ingredient and an auxiliary material.
  • the main ingredient of the main ingredient is the raw material of health care products, which refers to foods with specific drape function or for the purpose of supplementing vitamins and minerals. It is suitable for a specific group of people to eat foods that have the function of regulating the body, do not treat diseases, and cause any acute, subacute or chronic harm to 4 cups.
  • the main components of the preparation including but not limited to traditional Chinese medicine or natural source materials, chemicals and biological products, are deleted individually or in combination. It can be selected from, but not limited to, one or more of the following components: vitamins and provitamins, minerals, fungi, probiotics, edible fungi, amino vines, proteins and peptides, enzymes, microbial ferments, polysaccharides, Chinese herbal medicines ( Chinese herbal medicines), dietary fiber, spices, tea, edible or medicinal flowers, pollen and bee products. Some ingredients may be species of animal and plant and mineral-derived substances in the non-traditional Chinese medicine category.
  • the main component may be in the form of a virgin medicinal material, a fresh drug, a decoction piece, a granule, a powder, an extract and a purified or semi-synthetic product thereof, a synthetic or semi-synthetic product, an extract and a purified or purified product thereof, a fermentation product, and 7 Or a mixed or combined form of an enzymatic hydrolysate, an effective part, a monomer component, or the like.
  • a functional filler may be added to the main material, and the functional filler accounts for not more than 98% by weight of the main material.
  • the volatile and oily components in the main component may be directly added as an oily dispersant, or may be added as a solid component after solidification (including inclusion, adsorption, solid dispersion, etc.) of the functional filler to protect the component from being prepared. Loss in.
  • a functional filler can be added to improve the dosage and stability of preparation and administration.
  • a functional filler may also be selectively added to the main material.
  • a filler such as lactose, dextrin, and modified starch is often added before drying to avoid sticking during drying.
  • the main ingredient is a live bacterial preparation, it is easy to oxidize and react with heat and unstable components, and it is often used to remove the coating, embedding, m pretreatment process, and use functional fillers.
  • Functionally filled but not limited to, high molecular weight polymers, sugars, cellulose and its derivatives, starch and its derivatives, cyclodextrin and its derivatives, polymers, inorganic salts, pH regulators .
  • high-molecular polymers of natural origin include, but are not limited to, shellac, peach gum, gum arabic, xanthan gum, locust bean gum, Guaiac gum, bismuth gum, pectin, carrageenan, gelatin, karaya gum, Indian gum, white gum, celery gum, red gum, xihuang 3 ⁇ 4, xihuang gum, card, tower Suspect, locust bean gum, guar gum, acacia gum, ancient gum, English bean gum, paulownia gum, carrageenan, seaweed salt, apricot gum, agar, dextran, shell and its derivatives Things, 33 ⁇ 4 ⁇ , casein, etc.
  • Sugars include but are not limited to:
  • Glucose fructose, sucrose, brown sugar, brown sugar, sucrose, occupation, starch sugar, malt mash, vermiculite, lactose, dextrin, erythritol, alcohol, fructositol, mannitol, sorbitol, lactose Alcohol, galactitol, maltitol, isomalt, isomalt, paraquat, isomalt, oligo-isomalt, arabitol, oligo-isomalt, oligosaccharide, galactooligosaccharide , oligomannose, oligofructose, oligosaccharide, low 3 ⁇ 4 «, oligoglucosamine, oligofructose, oligosaccharide, low poly cane fructose, branched oligofructose, cow oligosaccharide, seaweed Sugar, chitosan oligosacchari
  • Cellulose and its derivatives include but are not limited to:
  • Starch and its derivatives include but are not limited to:
  • Modified starch carboxymethyl starch, sodium carboxymethyl starch, methylol starch, hydroxy starch propionate, ? Gelatinized starch, dextrin, etc.
  • Cyclodextrins and their derivatives include, but are not limited to:
  • Cyclodextrin methyl cyclodextrin, hydroxypropyl cyclodextrin, hydroxyethyl cyclodextrin, polymer cyclodextrin, ethyl cyclodextrin, branched cyclodextrin, and the like.
  • Poly includes but is not limited to:
  • Polyvinyl alcohol polyvinyl butyral, styrene-vinyl pyridine copolymer, acrylic resin, arsenic acid tree (card surface, crospovidone, povidone, polyvinyl acetate, acrylic acid Ester copolymer, polylactic acid, polyamino acid, polycarboxyacetic acid, polyethylene glycol, polyether, ion exchange resin, and the like.
  • Inorganic materials include but are not limited to:
  • Talc powder calcium carbonate, carbon hard, sulfur, calcium hydrogen hydride, phosphorus silicate, magnesium oxide, aluminum hydroxide, silicon dioxide, activated clay, alumina, sodium chloride, titanium dioxide, and the like.
  • ⁇ modifiers include, but are not limited to:
  • Carbon surface, carbon Wei potassium sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, phosphorus with dipotassium, citric acid, tartaric acid, succinic acid, fumaric acid, adipic acid, malic acid, lactic acid and the like.
  • Oily dispersant oily dispersant:
  • the melting point of the oily dispersant needs to satisfy the solid form of the finished preparation at normal temperature, and the oily dispersant melts when it is close to the human body #3 ⁇ 4.
  • the melting point of the preparation is between 23 and 46 ° C, more preferably between 3 ⁇ 426 and 39 ° C, and optimal between 7 and 36 ° C.
  • the melting point is high Immediate release tt ⁇ , the lower the melting point, the easier the finished product is to save.
  • the melting point can be as low as 18 °C.
  • the melting point of the formulation essentially depends on the melting point of the oily dispersant.
  • the oily dispersant is used alone or in combination of fats and oils, and the blending amount of the oil or the oil of two or more different melting points is adjusted to meet the melting point requirement of the preparation.
  • the melting point of the oil used in the oily dispersing agent is generally i ⁇ 20 ⁇ 70 ° C, preferably the melting point is in the range of 10 ° C to 60 ° C, more preferably the melting point is in the range of 22 to 40 ° C, and most preferably the melting point is Between 26 and 36 ° C.
  • the oily dispersant includes, but is not limited to, Ai oils, natural oils or processed (including but not limited to refining, refining, degumming, wintering, crystallization separation, hydrogenation, solidification, transesterification, esterification, beach reorganization, sub-division) Oils for lifting, upgrading, oil-hydrogen separation, hydrolysis, alcoholysis, turning and other oil processing methods, which are formed alone or in combination.
  • the oily dispersant can be classified into two types, namely vegetable fats and animal fats.
  • the vegetable oil and fat refers to vegetable-derived fats and oils, including sputum, not limited to vegetable oils, refined vegetable oils, and hydrogenated vegetable oil-refined vegetable oils.
  • vegetable oils palm kernel oil, coconut oil, corn oil, soybean oil, rapeseed oil, cottonseed oil, peanut oil, sunflower oil, sesame oil, miscellaneous oil, olive oil, safflower oil, kapok oil, evening primrose oil, cattle Oil tree oil, juniper oil, wheat germ oil, Litsea cubeba oil, fragrant fruit fat, black glutinous rice, peach kernel oil, walnut oil, grape seed oil, sea buckthorn oil, pumpkin seed oil, pine nut oil, canola oil, Apple seed oil, pomegranate seed oil, su seed oil, carrot seed oil, blackcurrant oil, perilla oil, broccoli oil, sesame oil, castor oil, almond oil, babassu oil, tea tree oil, tea seed oil, camellia oil, Hazelnut oil and the like are processed or un
  • the animal fat refers to animal-derived fats and fats, including but not limited to butter, cream substitutes, and used butter, chicken oil, sheep oil, lard, fish oil, whale oil, porpoise, squalene, etc. They are processed or unprocessed as raw materials, they are used in combination or in combination.
  • Oily dispersants may also be surfactants that are soluble in oils and fats, including but not limited to lecithin, polyethylene glycol (PEG), polyether (poloxamer), span, tween, sucrose fatty acids.
  • Esters mono-fatty acid glycerides, di-fatty acid glycerides, tri-fatty acid glycerides, polyglycerol fatty acid esters, alcoholic anhydride mono-fatty acid esters, sorbitan fatty acid esters, fatty acids and derivatives thereof, stearyl alcohol, Cetyl alcohol, semi-synthetic fatty acid esters, propylene glycol fatty acid esters, organic acid monoglycerides, monohydric alcohols, which are used in combination or in combination, partially or completely in place of vegetable oils or animal fats. : The amount of the oily dispersant to be added needs to satisfy the formulation in the state of charge, and the oil is 3 ⁇ 4 ⁇ phase.
  • the main material also contains a certain amount of oily components, it can be used as a substitute for some oily dispersants, and the addition of the oil dispersant can be adjusted as needed.
  • the oil's thief in the main ingredient may affect the melting point of the finished product, and the melting point of the oily dispersant may be adjusted as needed.
  • the freezing point and the melting point of the oil may be different, and sometimes the difference in melting point of the different crystals formed by the oil may occur.
  • the crystal type and proportion may be adjusted to adjust the point (commonly known as temperature regulation) to form a high melting point crystal to improve stability. .
  • excipients - water-soluble dispersants, flavoring agents, emulsifiers, etc.
  • the oil in the oral cavity can be absorbed and dissolved after the oily dispersant is melted, thereby further improving the immediate release characteristics of the present J agent.
  • the composition of the water-soluble dispersant is a sugar, and its main feature is water solubility, which is divided into monosaccharides, disaccharides, sugar alcohols, oligosaccharides and polysaccharides.
  • the saccharide includes, but is not limited to, glucose, fructose, sucrose, brown sugar, brown sugar, white sugar, rock sugar, fermented fiber, maltose, Verbasin, lactose, dextrin, erythritol, alcohol, fructitol, mannitol, sorbitol, lactitol, galactitol, maltitol, isomalt, isomalt, pras Alcohol, isomalt, oligo-isomalt, arabitol, oligo-isomalt, soy oligosaccharide, galactooligosaccharide, oligomannose, oligofructose, oligo-maltose, oligomeric oligoglucosamine Sugar, oligofructose, oligosaccharide, low poly cane fructose, branched oligofructose, cow oligosaccharide, trehalose,
  • the water-soluble dispersing agent may also be a water-soluble honey, a royal jelly, an amino acid, an amino acid salt, a salt, a peptide, or a protein, which may be used singly or in combination.
  • the main ingredient sometimes has a certain water-soluble component, which can replace the water-soluble dispersant to some extent.
  • the addition or addition ratio of the water-soluble dispersant can be determined according to the content of the water-soluble component in the specific main ingredient. If the main material is a water extract, it is possible that the water-soluble dispersant is not added or added less.
  • Water-soluble dispersing agents generally have a flavoring function. If the amount of addition is not enough, no addition or insufficient flavoring ability, it is necessary to add 5 tongues as a flavoring agent.
  • Flavoring agent In order to improve the mouthfeel of the preparation, a flavoring substance (flavoring agent) may be added. The flavoring agent may be selectively added according to the mouth of the main ingredient and the final product positioning. Flavoring agents include, but are not limited to, non-sugar sweeteners, aromatics II, inclusion agents, adsorbents, flavoring agents, sour agents, flavoring agents, flavoring agents; also include, but are not limited to, coffee, milk powder commonly used in the food industry. , cream, vanillin, ethyl maltol and food flavors, spices.
  • flavoring agent contains grease or surfactant
  • S ⁇ can be used as a substitute for some oily dispersing agent, and the addition of the oily dispersing agent can be adjusted according to the need.
  • Emulsifiers To help form the continuous phase of the oil, an active agent is added to reduce the surface energy.
  • the surfactant is used in a water-in-oil type to reduce the viscosity of the material or reduce the amount of grease. It can also be formulated with a water-in-oil/oil-in-water surfactant. If the oily dispersant in the formulation already contains a surfactant, this can also be omitted.
  • Surfactants include, but are not limited to, lecithin, polyethylene glycol (PEG), poloxamer, span, tween, sucrose fatty acid esters, mono-fatty acid glycerides, di-fatty acid glycerides , triglyceride, polyglycerol fatty acid ester, xylitol monoester, sorbitan, fatty acid, hexadecanol, cetyl alcohol, semi-synthetic fatty acid ester , propylene glycol fatty acid ester, organic acid monoglyceride, monool fatty acid ester.
  • the weight percentage of the main material and the auxiliary material the weight percentage of the main material in the proportion of the overall formulation of 0. 1% ⁇ 80%, the weight percentage of the auxiliary material accounted for 20% ⁇ 99. 9% of the overall preparation ratio.
  • the preparation of the slurry firstly refines the solid particles, and also liquefies the refined solid particles, and uniformly disperses the refined solid particles in the oily dispersant, and the final fineness of the refining is the weight of the preparation. 95% is below 200 «, the liquefaction process is to disperse the solid particles with the oily dispersant by means of stirring; the weight percentage of the oily dispersant should be equal to not less than 15% of the oil content in the finished product, in the case of 22 ⁇ 60 ° C can be free (or forced) under the flow of cattle; added according to oily dispersant
  • Different stages are: dry pulverization, semi-dry pulverization or wet pulverization; wherein wet pulverization can also be carried out simultaneously with both refining and liquefaction, and dry pulverization and semi-dry pulverization can also be deleted.
  • the refining method may be a grinding method, which may be a roll grinding method, a fine grinding method, a ball milling method, a vibration grinding method or a mixing method.
  • ⁇ Liquefaction is a necessary process for the solid raw material to become a slurry. The purpose is to make the solid material into a dispersed phase (non-continuous phase) and the oily dispersant as a liquid continuous phase. Stirring is a necessary means to achieve dispersion.
  • the temperature of the oily dispersant must be such that the oily dispersant in the material is in liquid form, in principle not less than 22 ⁇ (when the liquid oil is crystallized, it will appear below the melting point but still liquid), generally 26 ⁇ or more;
  • the oily dispersant should reach the continuous phase and ensure that the weight percentage of the added amount should satisfy the oil content of the finished product not less than 15%, generally more than 20%.
  • three methods can be combined, such as fe3 ⁇ 4 dry pulverization, and some oily dispersant is added to the wet pulverization condition before the final fineness is reached, and then wet pulverization: final fine degree.
  • the combination of a smashing method is carried out in the order of dry 3 ⁇ 4 ⁇ semi-dry 3 ⁇ 4 ⁇ 3 ⁇ 4, combined in two or three ways.
  • Dry pulverization (Fig. 3): This process uses a method of refining and reliquefying. It is refined under the condition that the oil content of the material is low, and the material is pulverized in the form of a dry powder having fluidity. The addition or non-existing amount of the oily dispersant depends on whether the total oil content of the pulverized material satisfies the dry pulverization state and the process requirement, and the original oil content of the solid material is included in the total oil content.
  • Liquefaction is further carried out. ⁇ Add the remaining oily dispersant and stir evenly to form a slurry. The oily dispersant can be added in stages. This dry pulverization may be carried out by adding a part of the oily dispersant to a half-milling pulverization condition at any fineness before pulverization to the final fineness, and then semi-dry pulverization until final fineness.
  • the dry pulverization may also be carried out by adding a part of the oily dispersant to the wet pulverization condition at any fineness before pulverization to the final fineness> Further wet pulverization final fineness 0
  • Dry pulverizing equipment includes but is not limited to: vibrating mill, rotor mill, jet mill, ball mill, sand mill (bead mill), Raymond mill, planetary mill, impact mill, silver smash Machine, roller mill, vertical mill, etc.
  • Refinement ⁇ Carcass is the mixing of all oil-insoluble solid materials (main material and water-soluble dispersant), adding (or not adding) part of the oily dispersant, crushing to the final fineness, and after the fineness is reached, the wet half Dry state.
  • Liquefaction is further carried out. ⁇ Add the remaining oily dispersant and stir evenly to make the material discharge. The oily dispersant can be added in stages. This semi-dry pulverization may also be carried out by adding a part of the oily dispersant to the wet pulverized cake at any fineness before pulverization to the final fineness, followed by wet pulverization until final fineness.
  • Semi-dry pulverizing equipment includes but is not limited to: roller mill, vibrating mill, rotor mill, hammer mill, ball mill, sand mill (bead mill), drum refiner (scraper type grinding) Machine), colloid mill, etc.
  • the oil-insoluble solid materials (the main material and the water-soluble dispersant) are mixed, and some (or all) of the oily dispersant is added (or not added) to become a diesel material, and pulverized to a final fineness. After the fineness is reached, the oily dispersant can be added in stages.
  • Wet pulverizing equipment includes but is not limited to: drum refiners (scraper refiners), ball mills, sanders (bead mills), basket mills, roller mills, vibratory mills, rotor mills Machine, colloid mill, planetary mill, high shear dispersant, homogenizer, etc.
  • the addition of the oily dispersant needs to grasp the addition time and the addition amount according to whether the viscosity characteristics of the material are adapted to the process efficiency of the stage.
  • the final amount of finished product is based on the flow rate of 22 ⁇ 60 °C.
  • the original oil content of the solid material varies depending on the raw material. In some extreme cases, the original oil content of the solid material has reached the oil content requirement of the finished product, and it is not necessary to add an oily dispersant.
  • the oily dispersant is heated to a liquid state if it is solid at normal temperature.
  • the weight percentage of the oily dispersant added should satisfy the finished oil content of not less than 15%, more preferably not less than 20%, and most preferably not less than 26%.
  • the finished oil content refers to the sum of the weight percentage of the finished product including the oil, the oil-soluble surfactant and other oil-soluble substances in the finished product.
  • Final fineness of the preparation 95% of the weight of the preparation may be below 200 «(g
  • the preparation is preferably in the « state. If the rubber particles are coarse, there is a grainy feeling in the mouth, and it is difficult to make a living. The fineness can be detected before the molding or after the molding is heated or the solvent is added to the liquid hopper.
  • the feed size of the main material In order to improve the effect of the refining process, it is necessary to control the feed size of the main material to be less than 10 gallons, and the g3 ⁇ 4 sub-controlling is to control the main material below 10 mesh, and more preferably the main material is controlled to be more than 95% below 100 mesh, most The good thing is that the main material is controlled at 95% below 200 mesh.
  • Emulsifiers are commonly used in lecithin and can be added as needed during the molding process.
  • the preparation is a solid-dispersed hot-melt immediate release system
  • the solid material should be well dispersed in the oil phase dispersant and must be well stirred.
  • the process of refining the solid particles is also a process of stirring and dispersing, the oil dispersant is added in a high amount, the grinding process is liquid (slurry), and the refining and dispersing are simultaneously performed, and the solid particles are completed at the time of discharging. Refine and disperse.
  • the purpose of the agitation is to increase the uniformity of the solid material in the grease to prevent the formation of agglomerates, and to appropriately reduce the moisture.
  • the agitation here can also be referred to as refining.
  • the M1 is mixed to gradually open the agglomerated particles, and the oily dispersant is gradually applied to the surface of the solid particles. After the solid particles are completely wetted and coated by the oily dispersant, the oily dispersant is formed into a continuous phase and liquefied.
  • high stirring power is required, when oily dispersant When it becomes a continuous phase, the power is greatly reduced until the addition of the oily dispersant is completed. It is important to disperse the agglomerated particles before the power is greatly reduced. Otherwise, the grease forms a continuous phase and then the agglomerated particles are dispersed only by stirring the fine particles.
  • Cooling molding 3 ⁇ 4 ⁇ " 3 ⁇ 4 materials are used for thermal fluidity and curing properties, including mold, casting, flat casting, cold forming, cutting, extrusion, and release molding. Winding molding, etc.
  • the material which has been refined and liquefied (22 to 60 ° C) is quantitatively thrown into a predetermined mold, and then cooled, solidified, demolded, and taken out after packaging.
  • Planar casting means that the material (22 ⁇ 60.C) which has been refined and liquefied is quantitatively discontinuously poured on the surface of the stationary or continuous boat, and is solidified and taken out of the package.
  • Cold press molding means that the material that has been refined and liquefied (22 ⁇ 60°C) has not been cooled and molded, and is quickly cooled and formed by low temperature (less than 20 °C) metal mold positioning, demoulding, and taking out the package.
  • Cut-to-form means that the material which has been refined and liquefied (22 ⁇ 48 °C) is continuously extruded or thrown on the surface of static or continuous motion, quantitatively cut before solidification and solidification, and solidified and taken out of the package.
  • Extrusion means that the material that has been refined and liquefied (22 ⁇ 46 ° C) is extruded from two equal speed inwardly rotating circular rolls with symmetrical impressions before completely cooling and solidifying. After deburring, it can be polished, coated with sugar or film.
  • the mold release molding means that the material which has been refined and liquefied (22 to 60 ° C) is quantitatively poured into a predetermined mold, and then the seal is solidified, and may be sealed during solidification or after solidification. This method of mold is sold with the product.
  • Powder molding method The powder is solidified into powder and then pressed and formed.
  • the preparation of the powder or granules includes, but is not limited to, spray granulation, extrusion granulation, agitation granulation, cleavage, and the like.
  • the press forming method can be formed by a tablet press or other die pressing method.
  • the spray granulation method means that the material (22 to 60) which has been subjected to refining and liquefaction is sprayed as a mist by a spray head, and the cooled gas cools the moving mist to solidify the material into powder or granules.
  • the extrusion granulation method means that the material which has been subjected to refining and liquefaction (22 to 48 ° C) is continuously extruded into pellets by an extruder.
  • Stirring granulation method means that the material which has been refined and liquefied (22 ⁇ 46 ° C) is continuously stirred into granules or powder under the cooled cake.
  • the cutting method means that the refining and liquefaction will be completed. The solid material is cut into granules, smashed, pulverized, etc. to form granules or powder.
  • Granules or powders made by these methods can also be used directly.
  • the moisture content of the finished preparation should not be higher than 6% of the weight of the finished preparation, and the hazelnut is 3%.
  • the finished product of the present invention has a melting point of 23 to 46 ⁇ , and the preparation may be contained or chewed.
  • the process of chewing is a process in which mechanical energy is converted into heat energy, and the heat generated by chewing is also added to the oily dispersing agent to improve the exudation degree of the main component.
  • the preparation may also be heated into a paste or a liquid.
  • the preparation of the patent household can be compounded twice after molding, and the preparation prepared by the method of the patent can be used in combination, and the preparation can be used as a raw material of other dosage forms in combination with other ingredients.
  • the dosage form is solid or heated to a liquid or paste form, and the molding method can be formed according to the method of the patent, or can be formed according to other simultaneous molding methods.
  • the preparation is used as the outer shell, and liquid, paste or solid is added in the middle; filling ⁇ is filled into other foods in the form of slurry or solid form of the preparation.
  • the above methods can be used individually or in combination. ⁇
  • the invention provides a product oral immediate release preparation and a preparation method thereof, the advantages and effects thereof are as follows: the medicament prepared according to the method has wide adaptability, large drug loading amount, and can achieve a better taste. To improve the dispersion rate of the ingredients of the health care products in the mouth, the preparation of lOOOfflg can be fully liquefied within 10 ⁇ 20 seconds (this data will vary depending on temperature, formula and shape), and it is convenient to take without drinking water. .
  • Fig. 1 is a schematic diagram showing the existence state of various components in the best oral speed « ⁇ 1"
  • FIG. 2 is a flow chart of a method for manufacturing an oral release form of a health care product according to the present invention
  • Figure 3 is a dry pulverization process flow chart
  • Figure 4 is a semi-dry pulverization process flow chart
  • Figure 5 is a flow chart of the wet pulverization process
  • Figure 6 is a flow chart of the roll grinding process of the specific embodiment 1.
  • Figure 7 is a flow chart of the finishing process of the specific embodiment 2
  • Figure 8 is a flow chart of the ball milling process of the specific embodiment
  • Figure 9 is a flow chart of the vibration grinding method of the specific embodiment 4.
  • Figure 10 is a flow chart of the mixing method of the specific embodiment 5
  • Preparation of the slurry First, refine the ⁇ 3 ⁇ 4 by semi-dry method and roll grinding method (see Figure 6). Specifically: 200Kg of the main material is pulverized to 200 mesh, 300Kg of white sugar and 180Kg of hydrogenated vegetable oil (36 ⁇ 60°C) are added to be mixed, and it is pre-ground into a two-roll mill (or three-roll mill) to 60 ⁇ 130, and then five rolls. Grinding machine (or three-roll mill) grinds to 20 ⁇ 33 counties.
  • the material is put into the All-in-one (mixer) for refining (stirring) for 6 hours, during which time 90Kg of hydrogenated vegetable oil is gradually added according to the viscosity of the material, and 30Kg is reserved and added with lecithin one hour before the end.
  • This process can also be used as a raw material for the white beach. After mixing the ingredients, it is ground without a pre-grinding 3 ⁇ 43 ⁇ 4 ⁇ five-roll mill (or three-roll mill).
  • Molding After refining (stirring), the material is discharged, poured into a preset mold, and then P is solidified, and the package is taken out, 10g/piece.
  • the main ingredient is g, auxiliary material (sugar 300, hydrogenated vegetable oil smoked g, lecithin 10Kg)
  • (2) Preparation of prize materials Refining and liquefaction simultaneously carry out a “3 ⁇ 4 mixing method (see Figure 10). Specifically: 200Kg of the main material is pulverized to 300 mesh, 200Kg of pre-ground milk powder, 300Kg of white sugar and hydrogenated vegetable oil are added. 370Kg of mixed slurry, refining (stirring) or grinding in a refiner (mixer) or scraper refiner for 3 ⁇ 6 hours, reserved 30Kg hydrogenated vegetable oil (36 ⁇ 60:C) at the time of mitri and lecithin Join together.
  • Molding refining (stirring) or grinding to discharge, pouring into a preset mold, then cooling and solidifying, taking out the package, lOg/block.
  • the above-mentioned production process is controlled below 70 , and the comfort is below 60 ° C, and more preferably below 48 ⁇ .
  • the slurry before casting can be mixed with nuts such as nucleus, sesame or almond, m ⁇ .
  • the slurry should be kept flowing (generally 31 ⁇ or more), and the form of the nuts can be Granules, granules or granules.
  • the straight cake can be solidified or placed in a preset mold and then cooled and solidified, and the package is taken out. This combination is one of the flexible applications of this patent, too
  • the oily dispersant of the preparation needs to receive the heat of the oral cavity and is converted into a liquid, and the solid particles wrapped in the oily dispersing agent are detached and released into contact with the saliva in the oral cavity, and then the solid formed by mixing and pulverizing is mixed.
  • the aqueous dispersant in the granules dissolves in the saliva in the oral cavity, so that the solid main component is rapidly dispersed in the oral cavity.
  • the aqueous dispersant and the main material must be evenly distributed in the oil dispersant, and the higher the aqueous dispersant is released, which is directly related to the dosage of the main component;
  • the agent should be as difficult as possible.
  • Increasing the melting rate of the oily dispersant can be solved by reducing the melting point of the oil, and the temperature effect of the finished product is: a more practical method is to add the amount of the oily dispersant to reduce the amount of heat absorbed from the mouth by the molten fat. Thereby improving the immediate release effect.
  • the material is exchanged with air at a certain temperature in the mixing and stirring (refining) process to evaporate water.
  • the process of mixing and stirring (refining) is the heat production process.
  • the proportion of oily components and the temperature of the ship's vertical material are in an effective viscosity.
  • the viscosity is higher: the higher the torque requirement of the equipment, the higher the heat production of the material. vice versa.
  • the material can be heated and ventilated. However, if it is required by the 3i process during the preparation process, it needs to be cooled.
  • the aforementioned grinding device can also achieve the effect of refining the material and evaporating the water by adjusting, ventilating or sealing the vacuum of the crushing chamber of the device.
  • the removal of 7j is not only beneficial to reduce the viscosity of the prize before the solidification » the amount of grease, but also the density of the solid discontinuous phase dehydration, improve the hardness of the finished product, help to form a good oil dispersion system, and prevent the moisture in the storage process.
  • External migration to improve the preservation of finished products. €S requires ®i to avoid solid non-phase hydration, improve oral release performance and improve the basic raw materials of the preparation.
  • the main ingredient is «#product raw material, the auxiliary material is oily.
  • the preferred ratio of the oily dispersant is 23 to 56% by weight, and the weight percentage of the raw material of the health care product is 34 to 76. 9% emulsifier 0. ⁇ % 0 oily dispersant raw material emulsifier
  • the weight percentage of the water-soluble dispersing agent is 0. 1 ⁇ 76%, flavoring agent 0.
  • the weight percentage of the water-soluble dispersing agent is 0. 1 ⁇ 76%, flavoring agent 0. 0 ⁇ 36%, emulsifier 0. 1 ⁇ 100/ 0 .
  • the oral cavity immediate release preparation, the specific raw material combination paste is as follows:
  • the emulsifier is 0. 1 ⁇ 10%.
  • the weight percentage of the raw material of the health care product is 3 ⁇ 76.9%, and the emulsifier is 0.1 to 10%.
  • the weight ratio of the oily dispersant is 23 ⁇ 56%
  • the weight percentage of the raw material of the health care product is 0. ⁇ 76%
  • the weight percentage of the water-soluble medullary sputum is 0. 0 ⁇ 76%

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une préparation à libération rapide par voie orale et son procédé de production. La matière première de la préparation se compose de 0,1% à 80% en poids de composant de santé comme matière première principale et de 20% à 99% en poids de l'émulsifiant huileux comme adjuvant. Son procédé de production consiste notamment : à préparer la matière première, à affiner et fluidifier cette matière première pour former la suspension épaisse, et à mouler cette suspension épaisse. Au stade de l'affinage, la granulométrie finale de 95% en poids de la matière de la préparation est inférieure à 200 micron. Au stade de la fluidification, les particules solides sont dispersées dans l'émulsifiant huileux par agitation et l'émulsifiant huileux utilisé dans une proportion telle que le contenu huileux de la préparation n'est pas inférieur à 15% en poids.
PCT/CN2008/001889 2007-11-22 2008-11-19 Libération rapide dans la cavité buccale des produits de santé et procédé de préparation associé Ceased WO2009070978A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN200710188018 2007-11-22
CN200710188017 2007-11-22
CN200710188017.4 2007-11-22
CN200710188018.9 2007-11-22

Publications (1)

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WO2009070978A1 true WO2009070978A1 (fr) 2009-06-11

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PCT/CN2008/001889 Ceased WO2009070978A1 (fr) 2007-11-22 2008-11-19 Libération rapide dans la cavité buccale des produits de santé et procédé de préparation associé

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WO (1) WO2009070978A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102599601A (zh) * 2012-04-05 2012-07-25 刘冬梅 一种藏红花养生保健水及制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08333243A (ja) * 1995-06-05 1996-12-17 Nippon Kayaku Co Ltd 口腔内感触の良好な錠剤
CN1555812A (zh) * 2004-01-12 2004-12-22 北京正大绿洲医药科技有限公司 蜂胶滴丸及其制备方法
CN1561214A (zh) * 2001-09-27 2005-01-05 法马西亚公司 新制剂及其用途
CN1764440A (zh) * 2003-03-26 2006-04-26 辉瑞健康公司 包含活性成分和可可粉的制剂及其用途
US20060263397A1 (en) * 2002-12-12 2006-11-23 Wenji Li Free-flowing solid formulations with improved bio-availability of poorly water soluble drugs and process for making the same
CN101194916A (zh) * 2007-11-22 2008-06-11 何煜 一种口腔速释制剂及其制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08333243A (ja) * 1995-06-05 1996-12-17 Nippon Kayaku Co Ltd 口腔内感触の良好な錠剤
CN1561214A (zh) * 2001-09-27 2005-01-05 法马西亚公司 新制剂及其用途
US20060263397A1 (en) * 2002-12-12 2006-11-23 Wenji Li Free-flowing solid formulations with improved bio-availability of poorly water soluble drugs and process for making the same
CN1764440A (zh) * 2003-03-26 2006-04-26 辉瑞健康公司 包含活性成分和可可粉的制剂及其用途
CN1555812A (zh) * 2004-01-12 2004-12-22 北京正大绿洲医药科技有限公司 蜂胶滴丸及其制备方法
CN101194916A (zh) * 2007-11-22 2008-06-11 何煜 一种口腔速释制剂及其制备方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102599601A (zh) * 2012-04-05 2012-07-25 刘冬梅 一种藏红花养生保健水及制备方法
CN102599601B (zh) * 2012-04-05 2013-10-23 刘冬梅 一种藏红花养生保健水及制备方法

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