CN105121559A - Production of inorganic/organic composite materials by reactive spray drying - Google Patents
Production of inorganic/organic composite materials by reactive spray drying Download PDFInfo
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- CN105121559A CN105121559A CN201480019159.6A CN201480019159A CN105121559A CN 105121559 A CN105121559 A CN 105121559A CN 201480019159 A CN201480019159 A CN 201480019159A CN 105121559 A CN105121559 A CN 105121559A
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09C—TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES ; PREPARATION OF CARBON BLACK ; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS
- C09C1/00—Treatment of specific inorganic materials other than fibrous fillers; Preparation of carbon black
- C09C1/02—Compounds of alkaline earth metals or magnesium
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09C—TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES ; PREPARATION OF CARBON BLACK ; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS
- C09C1/00—Treatment of specific inorganic materials other than fibrous fillers; Preparation of carbon black
- C09C1/02—Compounds of alkaline earth metals or magnesium
- C09C1/021—Calcium carbonates
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09C—TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES ; PREPARATION OF CARBON BLACK ; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS
- C09C1/00—Treatment of specific inorganic materials other than fibrous fillers; Preparation of carbon black
- C09C1/02—Compounds of alkaline earth metals or magnesium
- C09C1/025—Calcium sulfates
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09C—TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES ; PREPARATION OF CARBON BLACK ; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS
- C09C1/00—Treatment of specific inorganic materials other than fibrous fillers; Preparation of carbon black
- C09C1/02—Compounds of alkaline earth metals or magnesium
- C09C1/028—Compounds containing only magnesium as metal
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09C—TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES ; PREPARATION OF CARBON BLACK ; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS
- C09C1/00—Treatment of specific inorganic materials other than fibrous fillers; Preparation of carbon black
- C09C1/04—Compounds of zinc
Abstract
Disclosed is a method for producing composite materials by reactive spray drying, wherein a liquid phase A, which contains inorganic cations, and a liquid phase B, which contains anions that form a salt which is insoluble in the mixture of the fluid phases in conjunction with the inorganic cations, are jointly sprayed with at least one multi-material nozzle, and wherein at least one hydrophobic active ingredient is present in dissolved form in at least one liquid spraying phase, and wherein the salt formed from the cations of phase A and the anions of phase B has a solubility of less than 0.02 mol/l in the neutral aqueous milieu.
Description
Describe
The present invention relates to the method being prepared inorganic-organic composite material by reaction spraying dry, the organic phase wherein in matrix material forms at least one organic active ingredients, and inorganic phase forms sl. sol. inorganic salt at the standard conditions.In addition, the present invention relates to corresponding matrix material and uses thereof.
The inorganic-organic material of the calcium carbonate that can embed based on biomolecules is that itself is known, and wherein said material is obtained by intermediate processing, and the activeconstituents be embedded in calcium carbonate matrix is water-soluble substances.Such as, the people such as A.Elabbadi, JournalofMicroencapsulation, 2011; 28 (1): 1-9 describe green tea extract microencapsulation in calcium carbonate and calcium phosphate particles.The people such as M.Fujiwara, ChemicalEngineeringJournal137 (2008) 14-22 describes encapsulated for water-soluble biological molecule such as bovine serum albumin in calcium carbonate micro-capsule.The people such as A.I.Petrov., Biotechnol.Prog.2005,21,918-925 also describe and by co-precipitation, water-soluble biological molecule such as bovine serum albumin are embedded or is adsorbed in calcium carbonate.
US2009/0104275 describes the preparation of the Regular Insulin of microencapsulation, and wherein microencapsulation can be undertaken by co-precipitation.
US2009029902 describes the mixture of calcium carbonate and protein and calcium carbonate binding domain.Described mixture can by obtaining from water-soluble serous precipitation.
WO2008000042 describes the nanoparticle formulations of the activeconstituents being slightly soluble in water, and wherein said preparation by grinding acquisition by activeconstituents together with water-soluble inorganic salt.
In WO0105731, by by melting the amorphous glass sample product that obtains of inorganic salt mixt and activeconstituents mechanically mixing and granulating.
WO2009077147 describes the pharmaceutical preparation by activeconstituents and particle alkalescence solids mixing being obtained, and wherein said alkali grain solid is basic metal or alkaline earth salt.
EP-A1905427 describes and embeds activeconstituents in inorganic matrix, wherein only describes inorganic salt soluble in water if sodium carbonate is as inorganic matrix.
WO2012/027378 describes the preparation of granular active ingredients preparation, wherein by inorganic carrier material such as calcium carbonate and hydrophobic drug activeconstituents coprecipitation in mixing section.
But a shortcoming of the intermediate processing in mixing section is the tendency that mixing section has fast blocking.In addition, coprecipitate has the trend of activeconstituents recrystallization, and it causes the release of activeconstituents poorer, and therefore causes the decline of bioavailability.
An object of the present invention is to provide the method that simple and economically feasible preparation comprises the inorganic-organic composite material of bioactive ingredients, which obviate the shortcoming of prior art.
Therefore, have been found that the method being prepared matrix material by reaction spraying dry, many substance nozzle are wherein used to be sprayed together with comprising the liquid phase B of negatively charged ion (forming the salt being insoluble to liquid phase mixture with inorganic cation) by the liquid phase A comprising inorganic cation, and wherein there is the hydrophobic active ingredient of at least one solubilized form at least one liquid phase, and the salt that the negatively charged ion of the positively charged ion of phase A and phase B is formed has the solubleness lower than 0.02mol/L in neutral aqueous medium.Neutral aqueous medium represents the pH of 7+/-0.5.Aqueous medium preferably represents the pure aqueous medium that there is not other solvent.The solubleness that solubleness refers at the standard conditions (at 20 DEG C and 0.101325MPa).
Hydrophobic active ingredient can be present in one of liquid phase A or B in dissolved form or can be introduced in described method with the form be dissolved in another kind of liquid phase.
In the context of the present invention, matrix material is those materials wherein a kind of component be embedded in another kind of component matrix.In the matrix material obtained by method of the present invention, hydrophobicity organic active ingredients is present in embedding form in the matrix (" base status ") of the salt of inorganic cation, and described base status exists with amorphous form.Hydrophobic active ingredient is also preferably metamict.Metamict represents that the activeconstituents that is no more than 5% weight or base status exist in crystalline form in this case, and this state is measured by XRD (X-ray diffraction) mode.
Applicable base status of the present invention is can under certain conditions by least two kinds of liquid phases are contacted the salt obtained, wherein one comprises inorganic cation mutually, and the second or another kind comprise the negatively charged ion forming the salt being slightly soluble in water with the positively charged ion of other liquid phase mutually.As defined, the salt obtained only is slightly soluble in water, but is soluble in acidic medium, decomposes sometimes.
According to the present invention, the inorganic cation of base status is the well-tolerated metallic cation of preferred physiology.Specifically, the positively charged ion be applicable to is calcium ion, magnesium ion or zine ion or its mixture.Particularly preferably be calcium ion.
When the present invention is for being insoluble to the salt in neutral aqueous medium described in obtaining, the counter ion be applicable to of base status are inorganic and both organic anions.The negatively charged ion be applicable to is also by cationic patterns affect.Therefore, such as, some calcium salts are slightly soluble in water, and corresponding magnesium salts is soluble in water.Therefore, for all negatively charged ion of hereafter specifying, the solubleness of possible salt should be determined.Because these are known in the literature, so those skilled in the art adopt plain mode to be possible.
The inorganic anion being slightly soluble in the base status of water obtained be applicable to is selected from carbonate, phosphate radical, sulfate radical or mixed anion, such as, and hydroxyapatite.
According to an embodiment, the applicable organic anion being slightly soluble in the base status of water is the organic mono-of physiological compatible or the negatively charged ion of polyprotonic acid.This embodiment relates to the base status of the calcium salt comprised as the salt being slightly soluble in water.The calcium salt be applicable to is selected from citrate of lime, calcium lactate and caoxalate.
Obtain liquid phase A by being dissolved in the medium of selection by corresponding diffluent salt, it comprises the to be formed positively charged ion being slightly soluble in the base status of water.The salt be applicable to is calcium chloride, nitrocalcite, lime acetate, magnesium chloride, magnesium nitrate, magnesium acetate, magnesium citrate, magnesium lactate, zinc chloride, zinc nitrate or zinc acetate.As being suitable for, described salt can also for the formation of their list-, two-or semihydrate.
As solution, the salt introduced in described method is following salt together with the positively charged ion being slightly soluble in the base status of water to be formed in liquid phase A: preferably salt soluble in water or that be soluble in organic solvent or organic-water mixture.
Together with the negatively charged ion being slightly soluble in the base status of water to be formed in liquid phase A as solution the salt introduced in described method be soluble in water or be soluble in hydrophilic organic solvent or the ammonium salt of soluble in water-organic mixture or an alkali metal salt.In addition, what be also applicable to is the molten magnesium salts of phase commute.Carbonate, supercarbonate, vitriol, phosphoric acid salt, hydrophosphate that the salt be applicable to is particularly soluble in water.In addition, the ammonium of organic salt such as citric acid, lactic acid or oxalic acid, basic metal or magnesium salts are applicable.Liquid phase B (introducing the anionic group being slightly soluble in the base status of water by it) is preferably water-based.Optionally, phase B can also comprise organic solvent.
How the salt component of liquid phase A and B combines depends on the required type being slightly soluble in the base status of water.It is evident that, for the base status being slightly soluble in water, can not simultaneously as the positively charged ion providing anionic group be dissolved in liquid phase B as the positively charged ion providing cationic component to introduce liquid phase A.
The positively charged ion of liquid phase A under any circumstance must form the salt that the solubleness being slightly soluble in water is less than 0.02mol/L (at 20 DEG C and 0.1MPa) with the negatively charged ion of liquid phase B.
Therefore, such as, magnesium salts such as magnesium chloride can react with the volatile salt be dissolved in phase B or alkaline carbonate as the cationic salt that provides of phase A, obtains corresponding sl. sol. magnesiumcarbonate.Similar, such as, calcium salt such as calcium chloride can react as cationic salt and the magnesium salts be dissolved in the phase B such as magnesium citrate that provides of phase A, obtains corresponding sl. sol. citrate of lime.
For different liquid phases spraying be applicable to solvent in addition to water, or the hydrophilic organic solvent not limited with the miscibility of water, such as methyl alcohol, ethanol, glycerine, 1,2-propylene glycol, low molecular poly, such as PEG200, PEG300, PEG600 or acetone, acetonitrile, methyl-sulphoxide, dimethyl formamide, N-Methyl pyrrolidone, 2-methyl cellosolve or tetrahydrofuran (THF).The hydrophilic organic solvent used is preferably ethanol.
In solvent, the concentration of each feed material is that case is specific, and depends on the specific solubleness of used component.But, in the liquid phase, used salt component is preferably to the concentration of 0.1 to 10mol/L, is particularly preferably the concentration of 0.5 to 2mol/L.In liquid phase, the concentration of hydrophobic active ingredient can be 1 to 100g/L, preferably 10 to 40g/L.
Base status as the spray-dired target material of reaction no longer dissolves in the solvent mixture of liquid phase, and is slightly soluble in (lower than 0.02mol/L) in water.
According to an embodiment, hydrophobic active ingredient component is introduced in described method by organic solution, and the mixture of all liquid phases forms water-ORGANIC SOLVENT MIXTURES.
For all embodiments of hereafter specifying, when with an organic solvent, preferably use ethanol.
According to an embodiment, phase A comprises the mixture of water and organic solvent, and comprises hydrophobic active ingredient, and phase B is the pure water phase not comprising other solvent.According to further embodiment, phase A and B is pure water phase, and hydrophobic active ingredient is introduced spray method in other being dissolved in the liquid phase of organic solvent.According to another embodiment, be pure water phase mutually, and phase B is the water-organic phase also comprising hydrophobic active ingredient.
According to further embodiment, different hydrophobic active ingredient can also be introduced in described method.These compositions can also be dissolved in together a kind of mutually in or by different introducings mutually.
According to the embodiment of present invention further optimization, at least one tensio-active agent be added to one of liquid phase A or B or be optionally added to other liquid phase.According to one embodiment of the invention, hydrophobic active ingredient component is introduced in spray method by aqueous phase or water-organic phase therefore by also comprising at least one tensio-active agent.According to further embodiment of the present invention, hydrophobic active ingredient component is present in phase A together with tensio-active agent.According to one embodiment of the invention, hydrophobic active ingredient component is present in phase B together with tensio-active agent.According to further embodiment of the present invention, hydrophobic active ingredient component is present in other liquid phase together with tensio-active agent.According to particularly preferred embodiment, the liquid phase comprising tensio-active agent and hydrophobic active ingredient is pure water phase.
The tensio-active agent be applicable to is selected from the tensio-active agent of negatively charged ion, positively charged ion, nonionic and amphiphilic.
The anion surfactant be applicable to is the sodium salt of lipid acid and food fat acid, sylvite, magnesium salts and calcium salt particularly.The anion surfactant be applicable to is such as sodium lauryl sulphate, ammonium lauryl sulfate, lanette E, Docusate Sodium, docusate potassium or dioctyl calcium sulfosuccinate.
The cats product be applicable to is such as cetyl pyridinium
muriate.
In principle, the tensio-active agent be applicable to is the propylene glycol ester of the monoglyceride of lipid acid and food fat acid and triglyceride, acetic ester, lactate (such as stearyl-2-Sodium.alpha.-hydroxypropionate or calcium), citrate (such as triethyl citrate), tartrate (such as octadecyl tartrate), diacetyl tartaric acid ester, the acetic acid of mixing and tartrate, lipid acid and the sugar ester of food fat acid, sugared glyceryl ester, the propylene glycol ester of food fat acid, poly-ricinolic acid polyglycerol ester or food fat acid.
The nonionogenic tenside be applicable to is such as fatty alcohol and sterol, such as hexadecanol, stearyl alcohol, cetostearyl alcohol or cholesterol.
The nonionogenic tenside be applicable to is such as anhydro sorbitol, and it can also be polyoxyalkylated, such as Arlacel-60, sorbitan monostearate, Arlacel-20, polyoxyethylene-sorbitan mono-oleate, Arlacel-40, Polysorbate 20 (polyoxyethylene-(20) Arlacel-20), polysorbate 21 (polyoxyethylene-(4) Arlacel-20), Polysorbate 40 (polyoxyethylene-(20) Arlacel-40), Polysorbate 60 (polyoxyethylene-(20) Arlacel-60), polysorbate 61 (polyoxyethylene-(4) Arlacel-60), Polysorbate 65 (polyoxyethylene-(20) anhydro sorbitol three stearic acid ester), Polysorbate 80 (polyoxyethylene-(20) polyoxyethylene-sorbitan mono-oleate), sorbimacrogol oleate 100 (polyoxyethylene-(5) polyoxyethylene-sorbitan mono-oleate), Polysorbate 85 (polyoxyethylene-(20) sorbitan trioleate) or polysorbate 120 (polyoxyethylene-(20) sorbitan monoisostearate).
The nonionogenic tenside be applicable to or sucrose fatty ester, such as sucrose stearate, Surfhope SE Cosme C 1216, Surfhope SE Cosme C 1616, Sugar Ester O 1570, CE-1695, CT-1695, Sucrose myristate, sucrose pelargonate, sucrose undecylate, sucrose tridecylic acid ester, sucrose pentadecanoic acid ester or sucrose margarate.
What be also applicable to is polyoxyethylene fatty glyceride ester, such as Macrogol-1500 ricinolein, Macrogol glycerol monohydroxystearate Ph.Eur. (Kolliphor
tMrH40), Macrogol glycol ricinoleate Ph.eur. (Kolliphor
tMeL), Macrogol-1000 glyceryl monolaurate, Macrogol-1000 Zerol, Macrogol-1000 glyceryl monooleate.
What be also applicable to is polyoxyethylene fatty acid ester, such as Macrogol-15 hydroxy stearic acid ester (Kolliphor
tMhS15), Macrogol stearate 400 (Ph.Eur.), polyoxyethylene glycol (polyoxyl)-40 stearate or polyoxyethylene glycol (polyoxyl)-50 stearate.
What be also applicable to is polyoxyethylene aliphatic alcohol ether, such as Macrogol lauryl ether, polyoxyethylene-23 lauryl ether or polyoxyethylene glycol (polyoxyl)-10 oleyl ether.
What be applicable to equally is glycerol fatty acid ester, such as Zerol.
The amphiphilic surfactant be applicable to is such as poloxamer, such as PLURONICS F87, poloxamer 237, Pluronic/Lutrol F 108 or poloxamer188, preferred PLURONICS F87.What be also suitable as amphiphilic surfactant is solubilizing polymers, and the multipolymer of such as Soluplus, PEG6000, N-caprolactam and vinyl-acetic ester, weight ratio is 13/57/30.The amphiphilic surfactant be applicable to or Yelkin TTS.
According to one embodiment of the invention, sodium lauryl sulphate is preferred tensio-active agent.
According to further preferred embodiment, the tensio-active agent of use is polyoxyethylenated castor oil and hydrogenated castor oil, such as Macrogol glycerol monohydroxystearate Ph.Eur. or Macrogol glycol ricinoleate Ph.Eur.
According to further preferred embodiment, the tensio-active agent of use be have PEG1000,1500 or 2000 tocopherol polyethyleneglycol succinate.
Tensio-active agent can add with the amount of 2 to 50% weight of the amount based on activeconstituents, preferably 5 to 45% weight.
Hydrophobicity organic active ingredients can be medicine or beauty and make-up activeconstituents, crop protection agents, nutritious supplementary or pigment.Hydrophobic active ingredient has the solubleness lower than 0.1g/L under 20 DEG C of pressure with 0.101325MPa in water.
Drugs hydrophobility activeconstituents can be such as: benzodiazepine
, hypotensive agent, VITAMIN, cytostatics-particularly taxol, narcotic, neuroplegic, antidepressive, antiviral agent, such as anti-HIV medicine, microbiotic, antimycotic agent, dementia resisting agent, mycocide, chemotherapy, urological drug (urologics), anticoagulant, tyrosine kinase inhibitor, sulfanilamide (SN), spasmolytic, hormone, immunoglobulin (Ig), serum, Tiroidina therapeutical agent, psychotropic, Parkinson medicinal and other anti-hypoerkinesia agent, medicament for the eyes, neuropathy preparation, Calcium Metabolism Regulation agent, muscle relaxant, narcotic, lipid lowerers, liver therapeutical agent, coronary artery medicinal (coronarydrugs), cardiac drug, immunotherapeutic agent, regulate peptide and their inhibitor, soporific, tranquilizer, gynecologic medicine, gout medicine, molten scleroproein agent, zymin and translocator, enzyme inhibitors, emetic, blood flow stimulant, diuretic(s), diagnostic reagent, cortin, cholinergic agents, courage therapeutical agent, Zhichuan agent, medicine for bronchitis (broncholytics), beta-blockers, calcium antagonist, ACE inhibitor, atherosclerosis drug, anti-inflammatory agent, anti-coagulant, hypotensive agent, hypoglycemia agent, anti-high osmotic agent (antihypertonics), antifibrinolysis agent, Anti-epileptics, antiemetic, toxinicide, antidiabetic, anti-arrhythmic agents, anti-anemia action agent, antiabnormal reaction agent, anthelmintic agent, analgesic agent, stimulant, aldosterone antagonists, anoretic (slimmingagents).
For preparing spray solution, in the solvent be applicable under single component being dissolved in often kind of situation.Different liquid phases is supplied to nozzle respectively.
The spraying plant of all routines is applicable to carry out method of the present invention.
The nozzle be applicable to is many substance nozzle, such as two-substance nozzle, three-substance nozzle or four-substance nozzle.Nozzle can also be assembled into so-called " ultrasonic nozzle ".
Described nozzle is obtained commercially itself.
In addition, according to bleed type, atomizing gas can also be supplied.The atomizing gas used can be air or rare gas element, such as nitrogen or argon gas.The gaseous tension of atomizing gas can be 1MPa absolute pressure, preferably 0.12 to 0.5MPa absolute pressure at the most.
According to an embodiment, wherein different liquid phases mixed in nozzle body, the special nozzle be then atomized also is applicable.
One embodiment of the invention as mentioned relate to ultrasonic nozzle.Ultrasonic nozzle can operate when being with or without atomizing gas.In ultrasonic nozzle, spraying is owing to making vibration mutually to be atomized.According to jet size and design, ultrasonic nozzle can with the frequency run of 16 to 120kHz.
The treatment capacity of the liquid phase of each nozzle spray is arranged by jet size.Treatment capacity can be that 500g/ is little of 1000kg/ hour.When producing commodity amount, treatment capacity preferable range is 10 to 1000kg/ hour.
If do not use atomizing gas, then liquid pressure can be 0.2 to 20MPa absolute pressure.If use atomizing gas, then liquid can not stressed supply.
In addition, by dry gas, such as one of air or mentioned rare gas element are supplied to spray drying unit.Can by dry gas in the same way or adverse current be supplied to spraying liquid, be preferably in the same way.The temperature that enters of dry gas can be 120 to 220 DEG C, preferably 150 to 200 DEG C, and leaving temperature is 50 to 90 DEG C.
As already mentioned, the order of magnitude of spray parameters to be used such as treatment capacity, gaseous tension or nozzle diameter is determined by the size of device completely.Described device is obtained commercially, and the corresponding order of magnitude is recommended by manufacturers usually.
According to the present invention, preferably carry out spray method and make the average droplet size of spraying phase be 10 to 200 μm.Average droplet size by laser diffraction or can measure with the high-speed camera of image evaluation coupling.
Above about whole preferred and particularly preferred embodiment that the statement of spray method can be applicable to hereinafter described.Preferred spray parameters is also preferred with regard to following embodiment.
According to a preferred embodiment, the present invention relates to the method being prepared matrix material by reaction spraying dry, wherein use at least one many substance nozzle to comprise inorganic cation and form the salt of inorganic cation (wherein said salt is selected from calcium chloride, nitrocalcite, lime acetate, magnesium chloride, magnesium nitrate, magnesium acetate, magnesium citrate, magnesium lactate, zinc chloride, zinc nitrate and zinc acetate) solution liquid phase A and comprise the negatively charged ion that forms the salt being insoluble to liquid phase mixture with inorganic cation and form and be selected from acetate moiety, carbonate, bicarbonate radical, sulfate radical, phosphate radical, the ammonium of hydrogen phosphate and oxyhydroxide, the liquid phase B of the solution of basic metal or magnesium salts sprays together, and wherein at least one hydrophobic active ingredient exists with solubilized form with at least one liquid spray, and the salt that wherein positively charged ion of phase A and the negatively charged ion of phase B are formed has the solubleness lower than 0.02mol/L in neutral aqueous medium.The solvent of liquid phase used herein is preferably water or ethanol or water/alcohol mixture.
According to further preferred embodiment, the present invention relates to the method being prepared matrix material by reaction spraying dry, wherein use at least one many substance nozzle to comprise inorganic cation and form the salt of inorganic cation (described salt is selected from calcium chloride, nitrocalcite, lime acetate, magnesium chloride, magnesium nitrate, magnesium acetate, magnesium citrate, magnesium lactate, zinc chloride, zinc nitrate and zinc acetate) solution liquid phase A and comprise the negatively charged ion that forms the salt being insoluble to liquid phase mixture with inorganic cation and form and be selected from acetate moiety, carbonate, bicarbonate radical, sulfate radical, phosphate radical, the ammonium of hydrogen phosphate and oxyhydroxide, the liquid phase B of the solution of basic metal or magnesium salts sprays together, and wherein at least one hydrophobic active ingredient be dissolved in together with tensio-active agent at least one liquid spray mutually in form exist, and the salt that wherein positively charged ion of phase A and the negatively charged ion of phase B are formed has the solubleness lower than 0.02mol/L in neutral aqueous medium.The solvent of liquid phase used herein is preferably water or ethanol or water/alcohol mixture.The tensio-active agent used is preferably nonionogenic tenside.
According to a particularly preferred embodiment, the present invention relates to the method being prepared matrix material by reaction spraying dry, wherein use the liquid phase A comprising inorganic cation, and wherein liquid phase A forms the solution of the salt of inorganic cation, and described salt is selected from calcium chloride and lime acetate, and use the liquid phase B comprising the negatively charged ion forming the salt being insoluble to liquid phase mixture with inorganic cation, and the liquid phase B wherein used is the solution being selected from following salt: acetate moiety, carbonate, bicarbonate radical, sulfate radical, phosphate radical, the ammonium of hydrogen phosphate and oxyhydroxide or an alkali metal salt, and wherein use at least one many substance nozzle to be sprayed together with optional other liquid phase with B by liquid phase A, and wherein at least one hydrophobic active ingredient with at least one liquid spray mutually in solubilized form exist, and the salt that wherein positively charged ion of phase A and the negatively charged ion of phase B are formed has the solubleness lower than 0.02mol/L in neutral aqueous medium.The solvent of liquid phase used herein is preferably water or ethanol or water/alcohol mixture.The activeconstituents of preferred this paper is optionally dissolved in ethanol under the existence of tensio-active agent (be preferably nonionogenic tenside, and can add in phase A or add in phase B).Ammonium or an alkali metal salt of phase B are herein preferably acetate or carbonate.
If, according to mentioned above one preferably or in particularly preferred embodiment, nonionogenic tenside is for comprising in the liquid phase of hydrophobic active ingredient, then the fatty acid ester, particularly Macrogol hydroxy stearic acid ester of use polyoxyalkylated, Macrogol glycerol monohydroxystearate or Macrogol glycol ricinoleate is preferably.
The matrix material obtained forms the unbodied base status being slightly soluble in water, at least one activeconstituents embedding wherein will existed with amorphous form.In addition, described matrix material comprises water-soluble salt component.
The matrix material of the present invention using reaction spray technique to prepare has special advantage compared to the prior art.Surprisingly, compared with the precipitator method, significantly can reduce the reaction times by reaction spraying dry.Spray method generates can without the powder of the aftertreatment of complexity (filtration, follow-up drying) process further.
Compared with the method described, reaction spraying dry advantage is it based on can mass-producing (scalable) technology, and is easy to realize under gmp conditions.
Described mixture is specially adapted to have high-melting-point (>180 DEG C) and (the high-temperature decomposition of thermostability deficiency, melt decomposes), thus be not comparatively suitable for the preparation of the sl. sol. activeconstituents that ordinary method such as melt extrudes.
Compared with crystalline material, the significant rapider and activeconstituents release more completely of described mixture display in synthesis gastric juice.
As spray-dired powder, matrix material is applicable to solid administration forms process.
Such as, they are applicable to the particle being prepared viscosity by wet granulation (mixing tank or fluidized-bed), multipolymer, starch or gelatin by the homopolymer and multipolymer or NVP and vinyl-acetic ester that add tackiness agent such as Xylo-Mucine, Vltra tears, NVP such as PVP.
They are also applicable in interpolation or do not add dry adhesive such as
prepare dried particles when VA64Fine, such as, use roll squeezer.
In addition, described powder or particle can mix with other auxiliary material or activeconstituents, and can load in sachet and be used as redispersible powder agent.
In addition, described powder or particle can load in hard capsule.
In addition, described powder can be suppressed or particle obtains tablet, such as, by adding flowing regulator (Aerosil200=polymolecularity SiO
2), lubricant is Magnesium Stearate, calcium stearate, stearic acid, sodium stearyl fumarate, molecular-weight average M such as
wfor the PEG of 1000-8000, disintegrating agent such as Crospovidone or primojel.In addition, wetting agent such as PLURONICS F87 or sodium lauryl sulphate can also be added in press sheet mixture.
Matrix material of the present invention is also applicable to prepare effervescent tablet.At this, usually the effervescent mixture be made up of sodium bicarbonate and acid (citric acid or tartrate) is added in press sheet mixture.When matrix material of the present invention, depend on that composition may add sodium bicarbonate and prepare, if such as matrix is made up of calcium carbonate.In this case, the amount of acid is suitable for the amount of calcium carbonate.
Embodiment
Analytical procedure
Activeconstituents release is measured according to USP <711> chapter, stripping, paddle method device (100rpm).The amount of sample is normalized to 100mg activeconstituents.
Release medium A:0.08mHCl, pH1.1
Release medium B: as release medium A, but in addition the Polysorbate 80 of 0.1% weight is added in release medium.
Measure under 20+/-5 DEG C and normal atmosphere (0.101325MPa).
By XRD determining metamict.
Surveying instrument: diffractometer D8Advance, 9-times sample changer (Bruker/AXS)
Measure type: θ-θ geometry reflects
Angular region 2 θ: 2-80 °
Interval: 0.02 °
The Measuring Time of each angle intervals: 4.8 seconds
Divergent slit: there is 0.4mm orifice plate
mirror
Antiscatter slits: Soller slit
Detector: Sol-X detector
Temperature: room temperature
Embodiment 1
Danazol-compound of calcium carbonate
Phase A:CaCl
2, danazol
0.5mol/L is dissolved in the CaCl in ethanol
2, the concentration of danazol: 10g/L in solution
Phase B:0.5mol/LNa
2cO
3solution in deionized water
Spraying plant is the equipment being equipped with 0465555 type three-substance nozzle, from B ü chi, B290.
Spray parameters:
Spraying plant: B ü chiB290; Nozzle: exterior passage way 2.0mm diameter, interior passageway 0.7mm diameter, gas passage 2.8mm diameter
Atomizing gas: nitrogen, 819L/ hour
The pump treatment capacity of spraying liquid: 15mL/ minute
Dry gas: nitrogen, treatment capacity: 65m
3/ hour
Tower enters temperature: 180 DEG C
Tower leaves temperature: 62-65 DEG C
Release test: in release medium B after 120 minutes, releases the danazol of 10% weight.
According to XRD determining, described mixture is unbodied.
Embodiment 2:
The mixture of danazol-calcium carbonate and tensio-active agent
Phase A:0.25mol/L lime acetate in deionized water
Phase B: amine acetate 0.25mol/L, danazol 5g/L, Kolliphor
tMrH405% weight (based on activeconstituents).
The volatile salt of respective amount is dissolved in 150g deionized water, and mixes with the active ingredient solution of 300g ethanol.The mixture obtained is stirred until form clear soln at 40 DEG C.
120kHz ullrasonic spraying-dry nozzle that the nozzle used is 06-04-00445 type, is equipped with the 06-05-00290 type micropore kapillary introduced for double liquid.
Spray parameters:
Spraying plant: B ü chiB290; Ultrasonic nozzle: two-substance nozzle, Sonotek, power 5W
There is the cooling ultrasonic nozzle of 60% gas passage, cooling gas nitrogen, nozzle temperature 63 DEG C
The pump treatment capacity of spraying liquid: 4mL/ minute
Dry gas: nitrogen, treatment capacity: 65m
3/ hour, tower enters temperature: 130 DEG C,
Tower leaves temperature: 68 DEG C
Release test: in release medium A after 120 minutes, releases the danazol of 35% weight.
According to XRD, described mixture is unbodied.
Embodiment 3:
The mixture of danazol-calcium carbonate and tensio-active agent
Be similar to embodiment 2 to obtain and the Kolliphor as tensio-active agent
tMthe mixture of EL.
Release test: in release medium A after 120 minutes, releases the danazol of 35% weight.
According to XRD, described mixture is unbodied.
Embodiment 4
Estradiol-compound of calcium carbonate
Phase A:0.5mol/L calcium chloride and 10g/L estradiol solution in ethanol.
Phase B:0.5mol/LCaCO
3solution in deionized water.
The spraying plant used is the device being equipped with 0465555 type three-substance nozzle, from B ü chi, B290.
Spray parameters:
Spraying plant: B ü chiB290; Nozzle: exterior passage way 2.0mm diameter, interior passageway 0.7mm diameter, gas passage 2.8mm diameter
Atomizing gas: nitrogen, 819L/ hour
The pump treatment capacity of spraying liquid: 15mL/ minute
Dry gas: nitrogen, treatment capacity: 65m
3/ hour
Tower enters temperature: 170 DEG C
Tower leaves temperature: 48-52 DEG C
Release test: in release medium B after 120 minutes, releases the estradiol of 30% weight.
According to XRD determining, described mixture is unbodied.
Embodiment 5:
Itraconazole-compound of calcium carbonate
Phase A: lime acetate
0.25mol/L lime acetate is dissolved in ethanol.5g/L itraconazole is dissolved in THF, then by two kinds of solution mixing.Mixed ethanol/THF solvent mixture: 60/40 (ethanol/THF) 60/40
Phase B:0.25mol/L (NH
4)
2cO
3solution in deionized water.
The spraying plant used is the device being equipped with 0465555 type three-substance nozzle, from B ü chi, B290.
Spray parameters:
Spraying plant: B ü chiB290; Nozzle: exterior passage way 2.0mm diameter, interior passageway 0.7mm diameter, gas passage 2.8mm diameter
Atomizing gas: nitrogen, 819L/ hour
The pump treatment capacity of spraying liquid: 15mL/ minute
Dry gas: nitrogen, treatment capacity: 65m
3/ hour
Tower enters temperature: 210 DEG C
Tower leaves temperature: 68-72 DEG C
Release test: in release medium A after 120 minutes, releases the itraconazole of 30% weight.
According to XRD determining, described mixture is unbodied.
Embodiment 6
Naproxen Base-compound of calcium carbonate
Phase A: lime acetate
0.25mol/L is dissolved in the lime acetate of deionized water.
Phase B:0.25mol/L (NH
4)
2cO
3solution in deionized water/acetone (60/40) and 10g/L Naproxen Base
Spraying plant is the device being equipped with 0465555 type three-substance nozzle, from B ü chi, B290.
Spray parameters:
Spraying plant: B ü chiB290; Nozzle: exterior passage way 2.0mm diameter, interior passageway 0.7mm diameter, gas passage 2.8mm diameter
Atomizing gas: nitrogen, 819L/ hour
The pump treatment capacity of spraying liquid: 12mL/ minute
Dry gas: nitrogen, treatment capacity: 65m
3/ hour
Tower enters temperature: 220 DEG C
Tower leaves temperature: 68-70 DEG C
Release test: in release medium A after 120 minutes, releases the Naproxen Base of 45% weight.
According to XRD determining, described mixture is unbodied.
Embodiment 7:
Celecoxib-compound of calcium carbonate
Phase A:0.25mol/L lime acetate in deionized water
Phase B: amine acetate 0.25mol/L, celecoxib 5g/L, 5% weight Kolliphor
tMrH40, based on activeconstituents, in the mixture of deionized water and EtOH1:2 (weight ratio).
The volatile salt of respective amount is dissolved in 150g deionized water, and mixes with the active ingredient solution of 300g ethanol.The mixture obtained is stirred until form clear soln at 40 DEG C.
120kHz ullrasonic spraying-dry nozzle that the nozzle used is 06-04-00445 type, SonoTek, USA, be equipped with the 06-05-00290 type micropore kapillary introduced for double liquid.
Spray parameters:
Spraying plant: B ü chiB290; Ultrasonic nozzle: two-substance nozzle, Sonotek, power 5W
There is the cooling ultrasonic nozzle of 60% gas passage, cooling gas nitrogen, nozzle temperature 52 DEG C
The pump treatment capacity of spraying liquid: 4mL/ minute
Dry gas: nitrogen, treatment capacity: 65m
3/ hour, tower enters temperature: 132 DEG C,
Tower leaves temperature: 68-70 DEG C
Release test: in release medium A after 120 minutes, releases the celecoxib of 20% weight.
According to XRD, described mixture is unbodied.
Comparing embodiment I: the spraying of pure danazol
To spray as the phase B of spray solution (being similar to the solution that embodiment 2 obtains) under the spray condition provided in example 2.
Release test: in the release medium A of Polysorbate 80 comprising 0.1% weight after 120 minutes, release the danazol of 5 to 6.5% weight.
Comparing embodiment II: prepare danazol-compound of calcium carbonate by precipitation in mixing section according to WO2012/027378
Release test: in the release medium A of Polysorbate 80 comprising 0.1% weight after 120 minutes, release the danazol of 8% weight.
According to XRD, described product has a large amount of crystalline calcium carbonate fractions.
Accompanying drawing display is according to the blood plasma level of the matrix material of embodiment 1,2 and comparing embodiment I.
Following mensuration blood plasma level:
With identical order, substances is applied to each (weight in average 16kg) in 5 dogs, after each application, has the interval of 14 days.The preparation used is the physical mixture of 70% substances, 15%AvicelPH101 (FMCBioPolymer) and 15%KollidonCL (BASFSE) in hard gelatin capsule (TorpacInc., USA#11).Dosage is 30mg/kg, and to each animal and each Applicative time, dosage is separately based on ABW.Each dog capsule is given under fasted conditions.3,60,90 minutes and blood sampling in 2,4,8 and 24 hours after application.Water can arbitrarily obtain, and 4 hours feedings after application.Plasma sample is freezing, and subsequent analysis ((ESI (+)-LC-MS/MS) (post: AscentisExpressC18/2.7 μm/100mm × 2.1mm/Supelco) moving phase: the acetonitrile/water (50:50v/v) with 0.01% formic acid; Detection limit (quantitative limit (LoQ)): 2-5ng/mL)
The plasma concentration of activeconstituents is provided in the accompanying drawings with ng/mL.
Claims (amendment according to treaty the 19th article)
1. the method for matrix material is prepared by reaction spraying dry, wherein use at least one many substance nozzle by the liquid phase A comprising inorganic cation with comprise form the negatively charged ion of the salt being insoluble to liquid phase mixture with inorganic cation liquid phase B together with spray, and wherein at least one liquid spray mutually in there is the hydrophobic active ingredient of at least one solubilized form, and the salt that wherein positively charged ion of phase A and the negatively charged ion of phase B are formed has the solubleness lower than 0.02mol/L in neutral aqueous medium.
2. method according to claim 1, wherein the inorganic cation of phase A is selected from magnesium ion, calcium ion and zine ion.
3., according to the method for claim 1 or 2, the inorganic cation of wherein used phase A is calcium ion.
4. according to the method for any one in claims 1 to 3, wherein liquid phase A is the solution of the salt of inorganic cation, and described salt is selected from calcium chloride, nitrocalcite, lime acetate, magnesium chloride, magnesium nitrate, magnesium acetate, magnesium citrate, magnesium lactate, zinc chloride, zinc nitrate and zinc acetate.
5. according to the method for any one in Claims 1-4, wherein used liquid phase B is the solution being selected from following salt: the ammonium of carbonate, bicarbonate radical, sulfate radical, phosphate radical and bisulfate ion, basic metal or magnesium salts.
6. according to the method for any one in claim 1 to 5, wherein used liquid phase B is the solution being selected from following salt: the ammonium of citric acid, lactic acid and oxalic acid, basic metal or magnesium salts.
7., according to the method for any one in claim 1 to 6, the salt that wherein positively charged ion of phase A and the negatively charged ion of the phase B used are formed is the calcium salt being selected from carbonate, phosphate radical, sulfate radical, hydroxyapatite, citrate, lactate and oxalate.
8. according to the method for any one in claim 1 to 7, wherein liquid phase is solution, and the solvent existed is water or organic solvent or its mixture.
9., according to the method for any one in claim 1 to 8, wherein used organic solvent is ethanol.
10. according to the method for any one in claim 1 to 9, wherein said hydrophobic active ingredient with ethanol or water-ethanol solution form use.
Tensio-active agent, according to the method for any one in claim 1 to 10, is wherein added to and comprises in the liquid phase of hydrophobic active ingredient by 11..
Tensio-active agent, according to the method for any one in claim 1 to 11, is wherein added to the amount of 2 to 50% weight of the amount based on activeconstituents and comprises in the liquid phase of hydrophobic active ingredient by 12..
Tensio-active agent, according to the method for any one in claim 1 to 12, is wherein added to the amount of 2 to 50% weight of the amount based on activeconstituents and comprises in the liquid phase of hydrophobic active ingredient by 13..
The tensio-active agent of the fatty alcohol-ether of the fatty acid ester and polyoxyalkylated that are selected from polyoxyalkylated, according to the method for any one in claim 1 to 13, is wherein added to and comprises in the liquid phase of hydrophobic active ingredient by 14..
15. according to the method for any one in claim 1 to 14, and wherein used many substance nozzle are ultrasonic nozzle.
16., according to the method for any one in claim 1 to 15, wherein use atomizing gas during spraying dry.
17. according to the method for any one in claim 1 to 16, wherein generates the spray droplet of mean diameter 10 to 200 μm.
18., according to the method for any one in claim 1 to 17, wherein exist hydrophobic active ingredient in phase A.
19., according to the method for any one in claim 1 to 18, wherein exist hydrophobic active ingredient in phase B.
20. according to the method for any one in claim 1 to 19, and wherein phase A comprises calcium salt, and phase B comprises volatile salt or sodium carbonate.
21. according to the method for any one in claim 1 to 20, and wherein phase A comprises calcium salt, and phase B comprises amine acetate or sodium acetate.
22. matrix materials by obtaining according to the spray method of any one in claim 1 to 20, it is included in the amorphous hydrophobic active ingredient of at least one in amorphous salt matrix, and the solubleness of described amorphous salt matrix in neutral aqueous medium is lower than 0.02mol/L.
23. matrix materials according to claim 22, it is included at least one and is selected from the amorphous hydrophobic active ingredient of at least one in the amorphous salt matrix of the salt of calcium, magnesium and zinc salt.
24. according to the matrix material of claim 22 or 23, and it is included in the amorphous hydrophobic active ingredient of at least one in the amorphous salt matrix of calcium carbonate.
25. according to the matrix material of any one in claim 22 to 24, its also comprises surfactant.
26. matrix materials according to claim 25, it comprises the tensio-active agent of the polyoxyethylated ester being selected from Viscotrol C or hydrogenated castor oil.
27. matrix materials according to claim 25, it comprises the sodium lauryl sulphate as tensio-active agent.
Claims (27)
1. the method for matrix material is prepared by reaction spraying dry, wherein use at least one many substance nozzle by the liquid phase A comprising inorganic cation with comprise form the negatively charged ion of the salt being insoluble to liquid phase mixture with inorganic cation liquid phase B together with spray, and wherein at least one liquid spray mutually in there is the hydrophobic active ingredient of at least one solubilized form, and the salt that wherein positively charged ion of phase A and the negatively charged ion of phase B are formed has the solubleness lower than 0.02mol/L in neutral aqueous medium.
2. method according to claim 1, wherein the inorganic cation of phase A is selected from magnesium ion, calcium ion and zine ion.
3., according to the method for claim 1 or 2, the inorganic cation of wherein used phase A is calcium ion.
4. according to the method for any one in claims 1 to 3, wherein liquid phase A is the solution of the salt of inorganic cation, and described salt is selected from calcium chloride, nitrocalcite, lime acetate, magnesium chloride, magnesium nitrate, magnesium acetate, magnesium citrate, magnesium lactate, zinc chloride, zinc nitrate and zinc acetate.
5. according to the method for any one in Claims 1-4, wherein used liquid phase B is the solution being selected from following salt: the ammonium of carbonate, bicarbonate radical, sulfate radical, phosphate radical and bisulfate ion, basic metal or magnesium salts.
6. according to the method for any one in claim 1 to 5, wherein liquid phase B is the solution being selected from following salt: the ammonium of citric acid, lactic acid and oxalic acid, basic metal or magnesium salts.
7., according to the method for any one in claim 1 to 6, the salt that wherein positively charged ion of phase A and the negatively charged ion of phase B are formed is the calcium salt being selected from carbonate, phosphate radical, sulfate radical, hydroxyapatite, citrate, lactate and oxalate.
8. according to the method for any one in claim 1 to 7, wherein liquid phase is solution, and the solvent existed is water or organic solvent or its mixture.
9., according to the method for any one in claim 1 to 8, wherein used organic solvent is ethanol.
10. according to the method for any one in claim 1 to 9, wherein said hydrophobic active ingredient with ethanol or water-ethanol solution form use.
Tensio-active agent, according to the method for any one in claim 1 to 10, is wherein added to and comprises in the liquid phase of hydrophobic active ingredient by 11..
Tensio-active agent, according to the method for any one in claim 1 to 11, is wherein added to the amount of 2 to 50% weight of the amount based on activeconstituents and comprises in the liquid phase of hydrophobic active ingredient by 12..
Tensio-active agent, according to the method for any one in claim 1 to 12, is wherein added to the amount of 2 to 50% weight of the amount based on activeconstituents and comprises in the liquid phase of hydrophobic active ingredient by 13..
The tensio-active agent of the fatty alcohol-ether of the fatty acid ester and polyoxyalkylated that are selected from polyoxyalkylated, according to the method for any one in claim 1 to 13, is wherein added to and comprises in the liquid phase of hydrophobic active ingredient by 14..
15. according to the method for any one in claim 1 to 14, and wherein used many substance nozzle are ultrasonic nozzle.
16., according to the method for any one in claim 1 to 15, wherein use atomizing gas during spraying dry.
17. according to the method for any one in claim 1 to 16, wherein generates the spray droplet of median diameter μm.
18., according to the method for any one in claim 1 to 17, wherein exist hydrophobic active ingredient in phase A.
19., according to the method for any one in claim 1 to 18, wherein exist hydrophobic active ingredient in phase B.
20. according to the method for any one in claim 1 to 19, and wherein phase A comprises calcium salt, and phase B comprises volatile salt or sodium carbonate.
21. according to the method for any one in claim 1 to 20, and wherein phase A comprises calcium salt, and phase B comprises amine acetate or sodium acetate.
22. matrix materials by obtaining according to the spray method of any one in claim 1 to 20, it is included in the amorphous hydrophobic active ingredient of at least one in amorphous salt matrix, and the solubleness of described amorphous salt matrix in neutral aqueous medium is lower than 0.02mol/L.
23. matrix materials according to claim 22, it is included at least one and is selected from the amorphous hydrophobic active ingredient of at least one in the amorphous salt matrix of the salt of calcium, magnesium and zinc salt.
24. according to the matrix material of claim 22 or 23, and it is included in the amorphous hydrophobic active ingredient of at least one in the amorphous salt matrix of calcium carbonate.
25. according to the matrix material of any one in claim 22 to 24, its also comprises surfactant.
26. matrix materials according to claim 25, it comprises the tensio-active agent of the polyoxyethylated ester being selected from Viscotrol C or hydrogenated castor oil.
27. matrix materials according to claim 25, it comprises the sodium lauryl sulphate as tensio-active agent.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13154684 | 2013-02-08 | ||
| EP13154684.8 | 2013-02-08 | ||
| PCT/EP2014/051921 WO2014122077A1 (en) | 2013-02-08 | 2014-01-31 | Production of inorganic/organic composite materials by reactive spray drying |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105121559A true CN105121559A (en) | 2015-12-02 |
Family
ID=47666050
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480019159.6A Pending CN105121559A (en) | 2013-02-08 | 2014-01-31 | Production of inorganic/organic composite materials by reactive spray drying |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP2954009A1 (en) |
| JP (1) | JP2016507542A (en) |
| CN (1) | CN105121559A (en) |
| WO (1) | WO2014122077A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109111762A (en) * | 2018-10-09 | 2019-01-01 | 河南骏化发展股份有限公司 | A kind of preparation method of ink modified nano calcium carbonate |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9138381B2 (en) | 2013-02-08 | 2015-09-22 | Basf Se | Production of inorganic-organic composite materials by reactive spray-drying |
| EP2899162A1 (en) | 2014-01-22 | 2015-07-29 | Basf Se | Synthesis and use of CaSO4 based hardening accelerators |
| JP2019167319A (en) * | 2018-03-26 | 2019-10-03 | 株式会社親広産業 | Carbohydrate consumption promoter |
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2014122077A1 (en) | 2014-08-14 |
| EP2954009A1 (en) | 2015-12-16 |
| JP2016507542A (en) | 2016-03-10 |
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