CN104739776A - Solid dispersion composition of levocarnitine as well as preparation method and medical application of solid dispersion composition - Google Patents
Solid dispersion composition of levocarnitine as well as preparation method and medical application of solid dispersion composition Download PDFInfo
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Abstract
The invention provides a solid dispersion composition of levocarnitine and a preparation method of the solid dispersion composition. Sugar alcohol substances include one or more of fructose, xylitol, polydextrose, fructo-oligose, mannitol, cane sugar, glucose, resistant dextrin, sorbitol, maltose, isomaltulose alcohol, manoligosaccharides, dextrin, cyclodextrin, hydroxypropyl-beta-cyclodextrin, microcrystalline cellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, pre-gelled starch, starch, starch sugar, lactose, sodium carboxymethyl starch, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, Neotame and stevioside; the sugar alcohol substances are combined with the levocarnitine in a weight ratio of (13-50):1; the levocarnitine further comprises levocarnitine tartrate or levocarnitine hydrochloride. The solid dispersion composition has excellent moisture absorption resisting quality stability and is significant for the improvement of the product quality.
Description
Technical field
The present invention relates to a kind of healthy product compositions, and its preparation method and application, the specifically solid dispersion composition of levocarnitine, with and its preparation method and application.Healthy product compositions of the present invention, includes but not limited to medicine, nutritious health product, medical food, health food or functional food, bread and cheese etc.
Background technology
Levocarnitine, also known as L-carnitine, be natural materials in body required in mammal and the metabolism of people's energy i (in vivo), its major function promotes lipid metabolism.When ischemia, anoxia, acyl-CoA piles up, and Intramitochondrial long-chain acyl carnitine is also piled up, and free carnitine lowers because consuming in a large number.Ischemia, anoxia cause ATP level to decline, and cell membrane and Subcellular membrane permeability raise, and the acyl CoA of accumulation can cause membrane structure and change, film phase disintegrate and cause cell death.In addition, based on sugared anerobic glycolysis during anoxia, fatty acids etc. are piled up and are caused acidosis, ion imbalances, aqtocytolysis is dead, the free carnitine of q.s can make the acyl-CoA of accumulation enter in mitochondrion, reduces its suppression to acenine nucleotide translocase, makes oxidative phosphorylation smooth.Levocarnitine is the main energy sources of muscle cell especially myocardial cell, and many histoorgans such as brain, kidney are also mainly by fatty acid oxidation energy supply.Carnitine can also increase NADH cell C pigment reductase, the activity of cytochrome oxidase, the generation of acceleration ATP, participates in the Detoxication of some drugs.For various tissue ischemia anoxia, levocarnitine improves the energy supply of histoorgan by increasing energy generation.Other functions of levocarnitine have: the Oxidation of medium long-chain fatty acid; The Oxidation of fatty acid peroxidase; To the coenzyme A of combination and the cushioning effect of free both coenzyme As ratio; Produce power from letones, acetone acid, aminoacid (comprising branched-chain amino acid), removes the toxicity of too high coenzyme A, regulates ammonia density in blood.In addition, research shows, levocarnitine is also the significant energy source of seminal fluid nutrient substance.Human body lacks the series of symptoms produced because of carnitine, and clinical manifestation is as cardiomyopathy, skeletal myopathy, arrhythmia, hyperlipemia, and muscular spasm in hypotension and dialysis, and male is few, weak, asthenoteratozoospermia etc.
Levocarnitine also comprises its compound salt, such as levocarnitine tartrate, levocarnitine hydrochlorate, etc.
But disadvantageously, levocarnitine and salt thereof, be easy to the moisture absorption, this preparation for its preparation, storage, circulation etc. bring serious harmful effect, especially very unfavorable for production and processing and storage granules agent, powder product.
Summary of the invention
Inventor surprisingly finds; sugar alcohols material has certain moisture absorption protectiveness; in daily humidity environment; when levocarnitine or its salt and sugar alcohols material are mixed to form solid dispersion composition with certain proportion; well can improve the hygroscopicity of levocarnitine or its salt, improve the stability of its preparation.
Based on above research and practice, the invention provides the technology contents of following aspect:
First aspect, provide the solid dispersion of levocarnitine or its salt and sugar alcohols material, and preparation method thereof, compositions application and preparation;
Second aspect, provides the solid dispersion of a kind of levocarnitine or its salt and sugar alcohols material and other pharmaceutical carrier, and its preparation method, application.
" solid dispersion " of the present invention refers to and levocarnitine or its salt high uniformity is scattered in solid carrier (dispersion material), a kind of disperse system existed in solid form such as, formed in sugar alcohols material, or be highly dispersed in liquid-carrier the disperse system making solid preparation, the latter is as granule, powder.
First aspect, the object of this invention is to provide the solid dispersion composition of a kind of levocarnitine and sugar alcohols material, described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, and sugar alcohols material and levocarnitine are (13 ~ 50) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (15 ~ 20) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (15 ~ 45) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (17 ~ 40) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (18 ~ 38) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (20 ~ 35) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (22 ~ 30) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 50) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 45) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 40) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 34) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 35) with weight ratio: the ratio combination of 1;
Concrete, such as preferably sugar alcohols material and levocarnitine are that 13:1,14:1,15:1,16:1,17:1,18:1,19:1,20:1,21:1,22:1,23:1,24:1,25:1,26:1,27:1,28:1,29:1,30:1,31:1,32:1,33:1,34:1,35:1,36:1,37:1,38:1,39:1,40:1,41:1,42:1,43:1,44:1,45:1,46:1,47:1,48:1,49:1 or 50:1 equal proportion combines with weight ratio, and described levocarnitine also comprises levocarnitine tartrate or levocarnitine hydrochlorate.
Present invention also offers three kinds of preparation methoies of the solid dispersion of levocarnitine or its salt and sugar alcohols material:
Method one. dry pigmentation, the method comprises: get levocarnitine or its salt and sugar alcohols material respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, dry, granulate, and obtain solid dispersion, wherein said described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides,
Method two. wet granulation process, the method comprises: levocarnitine or its salt are dissolved in ethanol or ethanol-water solution, this dissolution homogeneity is sprayed on sugar alcohols material, carry out wet granulation, soft material processed, granulate, dry, granulate, namely solid dispersion is obtained, wherein said described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides,
Method three. solvent method, the method comprises: get levocarnitine or its salt and sugar alcohols material, add solvent, in 20 DEG C under solvent boiling point temperature range, stirring makes levocarnitine or its salt and sugar alcohols substance dissolves or is scattered in solvent, from this mixture, desolventizing is removed after mix homogeneously, and it is dry and pulverize and obtain solid dispersion, wherein said described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, described solvent selected from ethanol, water (such as distilled water or purified water) or ethanol water.In above-mentioned preparation, Rotary Evaporators can be taked to steam except desolventizing and dry method to remove, remove under reduced pressure, drying under reduced pressure, vacuum drying, lyophilization, spraying dry, fluid bed drying, one or more in heating, drying.
The above-mentioned preparation method of the present invention all can by levocarnitine or its salt and described sugar alcohols material dispersed, the solid dispersion obtained, pressed powder or the granule of high degree of dispersion, levocarnitine or its salt are highly dispersed in sugar alcohols material, under the effect of the blended dispersion of sugar alcohols material, and the gathering of sugar alcohols substance change levocarnitine or its molecules of salt or crystalline form, the hygroscopicity of levocarnitine or its salt can be made to significantly improve, the solid dispersion of levocarnitine or its salt and sugar alcohols material can see a kind of composition with pharmacologically active as, carry out useful in preparing drug formulations with this solid dispersion seem very easy and be easy to ensure the quality of pharmaceutical preparation.
Further, the invention provides and by the solid dispersion of the administration of any appropriate levocarnitine of the present invention or its salt and sugar alcohols material, but usually can pass through oral route.In order to carry out this kind of application, the solid dispersion of levocarnitine or its salt and sugar alcohols material can be prepared as acceptable any pharmaceutical dosage form on pharmaceutics by adding suitable pharmaceutical carrier, and but, the exact form of said composition depends on form of medication naturally.
Second aspect, provides the solid dispersion of a kind of levocarnitine and sugar alcohols material and the solid dispersion composition of other pharmaceutical carrier, and its preparation method, the pharmaceutical dosage form of described compositions is any pharmaceutical dosage form of acceptable on pharmaceutics, wherein said sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, and sugar alcohols material and levocarnitine are (13 ~ 50) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (15 ~ 20) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (15 ~ 45) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (17 ~ 40) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (18 ~ 38) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (20 ~ 35) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (22 ~ 30) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 50) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 45) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 40) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 34) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 35) with weight ratio: the ratio combination of 1;
Concrete, such as preferably sugar alcohols material and levocarnitine are that 13:1,14:1,15:1,16:1,17:1,18:1,19:1,20:1,21:1,22:1,23:1,24:1,25:1,26:1,27:1,28:1,29:1,30:1,31:1,32:1,33:1,34:1,35:1,36:1,37:1,38:1,39:1,40:1,41:1,42:1,43:1,44:1,45:1,46:1,47:1,48:1,49:1 or 50:1 equal proportion combines with weight ratio, and described levocarnitine also comprises levocarnitine tartrate or levocarnitine hydrochlorate;
And further, use corresponding pharmaceutical carrier or adjuvant, adopt different preparation technologies to can be made into different compound medicinal formulations.Be to be understood that, compound preparation refers to makes independent preparation using the solid dispersion of levocarnitine and sugar alcohols material as medicament active composition, it can be any pharmaceutical dosage form that pharmaceutics can accept, preferred oral preparation, such as tablet (comprises dispersible tablet, enteric coatel tablets, chewable tablet, oral cavity disintegration tablet, effervescent tablet, Deng), hard capsule (comprising enteric coated capsule), soft capsule, granule, powder, dry suspension, pill, pellet (comprising enteric coated micropill), drop pill, dry syrup, powder, oral solution, oral administration mixed suspension, and oral rapid release or the dosage form such as slow release or controlled release, etc., also can be the dosage form such as rapid release, slow release, controlled release of above various dosage form, such as oral dispersible tablet, slow releasing tablet, slow releasing capsule, enteric coatel tablets, effervescent tablet, oral cavity disintegration tablet, special-shaped tablets, born of the same parents rise granule, etc.Especially, by means known in the art preparation, be preferred for preparing oral solution, tablet (comprising dispersible tablet, slow-release tablet, enteric coatel tablets, effervescent tablet, oral cavity disintegration tablet, special-shaped tablets), capsule (comprising gastric solubleness, enteric, slow releasing capsule) that pharmaceutics uses.Described levocarnitine also comprises its compound salt, such as levocarnitine tartrate, levocarnitine hydrochlorate, etc.
Usually can give the active component of drug regimen with the solid dispersion form of levocarnitine and sugar alcohols material, but preferably give with Pharmaceutical composition form.Pharmaceutical composition of the present invention comprises the solid dispersion of levocarnitine and sugar alcohols material, and the drug regimen of the present invention of one or more pharmaceutically acceptable carriers or excipient.These carriers must be acceptable, can with other component compatibility of formula, and nontoxic to its receiver.When giving separately each component of said composition, they are each form of Pharmaceutical composition naturally generally; Unless otherwise indicated, the compositions of indication of the present invention refers to the drug regimen of the solid dispersion containing levocarnitine and sugar alcohols material.Described levocarnitine also comprises its compound salt, such as levocarnitine tartrate, levocarnitine hydrochlorate, etc.
Use corresponding, different pharmaceutical carriers and preparation technology, pharmaceutical composition of the present invention can be made different pharmaceutical dosage forms.What those skilled in the art were appreciated that is, these pharmaceutical carriers be become various dosage form for the ease of production and processing, guarantee medicine safe, effectively with the factor such as to stablize, and to select according to the physicochemical property of different pharmaceutical dosage forms and medicine self.The choice for use of pharmaceutical carrier is that those of skill in the art of the present invention know with apparent.
Be to be understood that, for oral agents, according to method well known in the art, usually according to the pharmaceutical carrier that different medicaments is selected or combinationally used, optionally comprise excipient or diluent, such as microcrystalline Cellulose, mannitol, non-dairy creamer, lactose, pregelatinized Starch, starch, dextrin, cyclodextrin, HP-β-CD, calcium phosphate, calcium hydrogen phosphate, hydroxypropyl emthylcellulose, sucrose, dextran, poloxamer, sodium chloride, sorbitol, glucose, polydextrose, oligofructose, Oligomeric manna sugar, resistant dextrin, fructose, water, Polyethylene Glycol, propylene glycol, glycerol, cyclodextrin, HP-β-CD and derivant thereof, coffee, milk powder, vegetable protein powder, etc., for oral solid formulation, optionally can also comprise binding agent, such as polyvidone (polyvinylpyrrolidone), methylcellulose, hydroxy methocel, hydroxypropyl methylcellulose, pregelatinized Starch, carboxymethyl starch sodium, hydroxypropyl cellulose, hydroxyethyl-cellulose, gelatin, guar gum, xanthan gum, etc., also comprise lubricant, such as magnesium stearate, stearic acid, Pulvis Talci, stearyl fumarate, sodium lauryl sulphate, etc., also optionally comprise disintegrating agent, such as carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, pregelatinized Starch, etc., also optionally comprise surfactant or cosolvent, such as sodium lauryl sulphate, Tween-80, etc., also can comprise pH value regulator or buffer agent or cosolvent, such as phosphate buffer, citric acid, sodium citrate, acetate buffer, dilute hydrochloric acid, lactic acid, sodium carbonate, sodium hydroxide, alkaline organic compound, as arginine, lysine, meglumine, trometamol, etc., also optionally comprise antiseptic, such as sodium benzoate, potassium sorbate, methyl parahydroxybenzoate, propyl p-hydroxybenzoate, etc., also optionally comprise stabilizing agent and antioxidant, such as metal chelating agent selects ethylenediaminetetraacetic acid and salt (calcium disodium edetate, disodium edetate) etc. thereof, sodium sulfite, sodium pyrosulfite, vitamin C, vitamin E, etc., also optionally comprise taste regulator, such as maltose alcohol, fructose, sucrose, saccharin sodium, flavoring orange essence, strawberry essence, etc., that also can comprise other routine in addition, appropriate additive.It is also understood that agent type be tablet or capsule time, can be film coating.For the material of film coating, comprise applicable coating materials, such as hydroxypropyl methylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate (enteric-coating material), etc.; Also can comprise plasticizer, such as Polyethylene Glycol, triethyl citrate, etc.; Also optionally comprise suitable solubilizing agent, as Polyoxyethylene Sorbitan Monooleate; Also can comprise suitable pigment, as titanium dioxide, various ferrum oxide, pink pigment, etc.Should be appreciated that above-mentioned " optionally comprising " refers to namely can optionally choice for use, also can not use.
In the present patent application, " compositions " refer on one or more described compounds or its physiology/pharmaceutically acceptable salt or prodrug, with other chemical composition, such as, on physiology/and the mixture that formed of pharmaceutically acceptable carrier or excipient, the object of pharmaceutical composition is conducive to the using of medicine, carries, preserves; " administration " mentioned here refer in order to prevent or disease therapy and to organism (comprising patient or healthy population) deliver described in compound, its pharmaceutically useful salt or its solvate.
Further, present invention also offers the preparation method of the pharmaceutical composition of the solid dispersion of levocarnitine and sugar alcohols material, it comprises and the solid dispersion of levocarnitine and sugar alcohols material and pharmaceutically acceptable pharmaceutical carrier is mixed and make acceptable any pharmaceutical preparation on pharmaceutics, the solid dispersion of such as levocarnitine and sugar alcohols material and pharmaceutical carrier dry powder blend, dry granulation mixing (dry granulating machine process), wet granulation mixing (with water or alcoholic solution wet granulation), liquid or semisolid mixes (as the content of soft capsule, drop pill dropping liquid mixes) etc., preferred pharmaceutical dosage form is granule, dry suspension, tablet (comprises dispersible tablet, enteric coatel tablets, chewable tablet, oral cavity disintegration tablet, effervescent tablet etc.), hard capsule (comprising enteric coated capsule), oral solution, dry syrup, powder, oral administration mixed suspension, soft capsule, pill, pellet (comprising enteric coated micropill), drop pill, and oral rapid release or the dosage form such as slow release or controlled release, also can be the rapid release of above various dosage form, slow release, the dosage forms such as controlled release, such as oral dispersible tablet, slow releasing tablet, slow releasing capsule, enteric coatel tablets, effervescent tablet, oral cavity disintegration tablet, special-shaped tablets, born of the same parents rise granule, etc.Especially, by means known in the art preparation, be preferred for preparing tablet (comprising dispersible tablet, slow-release tablet, enteric coatel tablets, effervescent tablet, oral cavity disintegration tablet, special-shaped tablets), capsule (comprising gastric solubleness, enteric, slow releasing capsule), oral solution etc. that pharmaceutics uses.
Preferably, the invention provides a kind of granule containing the solid dispersion of levocarnitine and sugar alcohols material, described sugar alcohols material and levocarnitine are (13 ~ 50) with weight ratio: the ratio combination of 1;
Preferred sugar alcohols material and levocarnitine are (15 ~ 20) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (15 ~ 45) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (17 ~ 40) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (18 ~ 38) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (20 ~ 35) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (22 ~ 30) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 50) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 45) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 40) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 34) with weight ratio: the ratio combination of 1,
Preferred sugar alcohols material and levocarnitine are (25 ~ 35) with weight ratio: the ratio combination of 1;
Wherein said described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, concrete, such as preferably sugar alcohols material and levocarnitine are that 13:1,14:1,15:1,16:1,17:1,18:1,19:1,20:1,21:1,22:1,23:1,24:1,25:1,26:1,27:1,28:1,29:1,30:1,31:1,32:1,33:1,34:1,35:1,36:1,37:1,38:1,39:1,40:1,41:1,42:1,43:1,44:1,45:1,46:1,47:1,48:1,49:1 or 50:1 equal proportion combines with weight ratio, and described levocarnitine also comprises levocarnitine tartrate or levocarnitine hydrochlorate, further, its preparation method comprises: sugar alcohols material is crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, is separately dissolved in 75% alcoholic solution by levocarnitine, is sprayed on by this dissolution homogeneity in the mixture of sugar alcohols material and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product,
Or its preparation method comprises: get levocarnitine, sugar alcohols material, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
Further, the solid dispersion of levocarnitine of the present invention or its salt and sugar alcohols material is preparing the application for the treatment of in myocardiac medicine; Application in the medicine of few, weak, the asthenoteratozoospermia of preparation treatment male.
Have now found that, the solid dispersion of levocarnitine of the present invention or its salt and sugar alcohols material, demonstrate unexpected advantage, well improve levocarnitine or its salt hygroscopicity, this preparation for its preparation, storage, circulation etc. are very important, especially highly beneficial for production and processing and storage granules agent, powder product, the raising for product quality or quality is very favourable.
detailed description of the inventionin implementation process of the present invention, those of ordinary skill in the art are not departing from the scope of the present invention various embodiment that the basis with spirit produces and are modifying apparent and be easily carry out.By the following examples application of the present invention etc. done and illustrate further, but do not represent embodiment limitation of the present invention.
The granule of the solid dispersion of embodiment 1, levocarnitine or its tartrate and sugar alcohols material and preparation thereof
Recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 10%, be preferably levocarnitine tartrate 3%,
Polydextrose 25% ~ 55%, is preferably 38%,
Fructose or xylitol 45% ~ 65%, be preferably fructose 59%;
Its preparation method comprises: polydextrose, fructose or xylitol are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of polydextrose and fructose or xylitol and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, polydextrose, fructose or xylitol respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
Wettability test: the granule getting the solid dispersion that the optimizing prescriptions in the present embodiment obtains, another configuration reference substance, reference substance is polydextrose and fructose according to the mixture of the proportions of optimizing prescriptions amount in the present embodiment and levocarnitine tartrate according to weight ratio is the obtained solid dispersion of 1:1; Study its hygroscopicity respectively;
Method: it is appropriate that precision takes product to be tested respectively, and be laid in (thickness is less than 5mm) at the bottom of weighing botle, the uncovered exsiccator being placed in different relative humidity, place 24 hours, taking-up is weighed, calculates rate of body weight gain, the results are shown in Table 1.
Table 1 hygroscopicity test results
Result shows, the granule of the solid dispersion that the present embodiment obtains, and its hygroscopicity, well below reference substance, has the significance difference opposite sex, embodies solid dispersion composition of the present invention and has good anti-moisture absorption quality stability.
The granule of the solid dispersion of embodiment 2, levocarnitine or its tartrate and sugar alcohols material and preparation thereof
Recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 10%, be preferably levocarnitine tartrate 5%,
Oligofructose 25% ~ 55%, is preferably 30%,
Resistant dextrin 50% ~ 75%, is preferably 65%;
Its preparation method comprises: oligofructose, resistant dextrin are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of oligofructose and resistant dextrin and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, oligofructose and resistant dextrin respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
Wettability test: the granule getting the solid dispersion that the optimizing prescriptions in the present embodiment obtains, another configuration reference substance, reference substance is oligofructose and resistant dextrin according to the mixture of the proportions of optimizing prescriptions amount in the present embodiment and levocarnitine tartrate according to weight ratio is the obtained solid dispersion of 1:1; Study its hygroscopicity respectively;
Method: it is appropriate that precision takes product to be tested respectively, and be laid in (thickness is less than 5mm) at the bottom of weighing botle, the uncovered exsiccator being placed in different relative humidity, place 24 hours, taking-up is weighed, calculates rate of body weight gain, the results are shown in Table 2.
Table 2 hygroscopicity test results
Result shows, the granule of the solid dispersion that the present embodiment obtains, and its hygroscopicity, well below reference substance, has the significance difference opposite sex, embodies solid dispersion composition of the present invention and has good anti-moisture absorption quality stability.
The granule of the solid dispersion of embodiment 3, levocarnitine or its tartrate and sugar alcohols material and preparation thereof
Recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 5% ~ 15%, be preferably levocarnitine tartrate 10%,
Oligomeric manna sugar 5% ~ 10%, is preferably 7.5%,
Sorbitol 50% ~ 75%, is preferably 65%;
Its preparation method comprises: Oligomeric manna sugar, Sorbitol are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of Oligomeric manna sugar and Sorbitol and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, Oligomeric manna sugar, Sorbitol respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
Wettability test: the granule getting the solid dispersion that the optimizing prescriptions in the present embodiment obtains, another configuration reference substance, reference substance is Oligomeric manna sugar and Sorbitol according to the mixture of the proportions of optimizing prescriptions amount in the present embodiment and levocarnitine tartrate according to weight ratio is the obtained solid dispersion of 1:1; Study its hygroscopicity respectively;
Method: it is appropriate that precision takes product to be tested respectively, and be laid in (thickness is less than 5mm) at the bottom of weighing botle, the uncovered exsiccator being placed in different relative humidity, place 24 hours, taking-up is weighed, calculates rate of body weight gain, the results are shown in Table 3.
Table 3 hygroscopicity test results
Result shows, the granule of the solid dispersion that the present embodiment obtains, and its hygroscopicity, well below reference substance, has the significance difference opposite sex, embodies solid dispersion composition of the present invention and has good anti-moisture absorption quality stability.
The granule of the solid dispersion of embodiment 4, levocarnitine or its tartrate and sugar alcohols material and preparation thereof
Recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 15%, be preferably levocarnitine tartrate 3%,
Hydroxyl isomaltulose 75% ~ 95%, is preferably 92%,
Carboxymethyl starch sodium 3% ~ 10%, is preferably 5%;
Its preparation method comprises: hydroxyl isomaltulose, carboxymethyl starch sodium are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of hydroxyl isomaltulose and carboxymethyl starch sodium and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, hydroxyl isomaltulose, carboxymethyl starch sodium respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
Wettability test: the granule getting the solid dispersion that the optimizing prescriptions in the present embodiment obtains, another configuration reference substance, reference substance is hydroxyl isomaltulose and carboxymethyl starch sodium according to the mixture of the proportions of optimizing prescriptions amount in the present embodiment and levocarnitine tartrate according to weight ratio is the obtained solid dispersion of 1:1; Study its hygroscopicity respectively;
Method: it is appropriate that precision takes product to be tested respectively, and be laid in (thickness is less than 5mm) at the bottom of weighing botle, the uncovered exsiccator being placed in different relative humidity, place 24 hours, taking-up is weighed, calculates rate of body weight gain, the results are shown in Table 4.
Table 4 hygroscopicity test results
Result shows, the granule of the solid dispersion that the present embodiment obtains, and its hygroscopicity, well below reference substance, has the significance difference opposite sex, embodies solid dispersion composition of the present invention and has good anti-moisture absorption quality stability.
The granule of the solid dispersion of embodiment 5, levocarnitine or its tartrate and sugar alcohols material and preparation thereof
Recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 15%, be preferably levocarnitine tartrate 5%,
Sucrose or glucose 75% ~ 95%, be preferably sucrose 90%,
Carboxymethyl starch sodium 2% ~ 8%, is preferably 3%,
Polyvinylpyrrolidone 1% ~ 5%, is preferably 2%;
Its preparation method comprises: by sucrose or glucose, carboxymethyl starch sodium, polyvinylpyrrolidone mistake 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of sucrose or glucose, carboxymethyl starch sodium and polyvinylpyrrolidone and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or, its preparation method comprises: get levocarnitine or its tartrate, sucrose or glucose, carboxymethyl starch sodium, polyvinylpyrrolidone respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
Wettability test: the granule getting the solid dispersion that the optimizing prescriptions in the present embodiment obtains, another configuration reference substance, reference substance is sucrose, carboxymethyl starch sodium and polyvinylpyrrolidone according to the mixture of the proportions of optimizing prescriptions amount in the present embodiment and levocarnitine tartrate according to weight ratio is the obtained solid dispersion of 1:1; Study its hygroscopicity respectively;
Method: it is appropriate that precision takes product to be tested respectively, and be laid in (thickness is less than 5mm) at the bottom of weighing botle, the uncovered exsiccator being placed in different relative humidity, place 24 hours, taking-up is weighed, calculates rate of body weight gain, the results are shown in Table 5.
Table 5 hygroscopicity test results
Result shows, the granule of the solid dispersion that the present embodiment obtains, and its hygroscopicity, well below reference substance, has the significance difference opposite sex, embodies solid dispersion composition of the present invention and has good anti-moisture absorption quality stability.
The granule of the solid dispersion of embodiment 6, levocarnitine or its tartrate and sugar alcohols material and preparation thereof
Recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 15%, be preferably levocarnitine tartrate 5%,
Mannitol 35% ~ 65%, is preferably sucrose 55%,
Lactose 25% ~ 55%, is preferably 40%;
Its preparation method comprises: mannitol, lactose are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of mannitol and lactose and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, mannitol, lactose respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
Wettability test: the granule getting the solid dispersion that the optimizing prescriptions in the present embodiment obtains, another configuration reference substance, reference substance is mannitol and lactose according to the mixture of the proportions of optimizing prescriptions amount in the present embodiment and levocarnitine tartrate according to weight ratio is the obtained solid dispersion of 1:1; Study its hygroscopicity respectively;
Method: it is appropriate that precision takes product to be tested respectively, and be laid in (thickness is less than 5mm) at the bottom of weighing botle, the uncovered exsiccator being placed in different relative humidity, place 24 hours, taking-up is weighed, calculates rate of body weight gain, the results are shown in Table 6.
Table 6 hygroscopicity test results
Result shows, the granule of the solid dispersion that the present embodiment obtains, and its hygroscopicity, well below reference substance, has the significance difference opposite sex, embodies solid dispersion composition of the present invention and has good anti-moisture absorption quality stability.
Embodiment 7,
The application of granule in the myocardiac medicine of preparation treatment of any one solid dispersion in embodiment 1 to embodiment 6; Application in the medicine of few, weak, the asthenoteratozoospermia of preparation treatment male.
Claims (10)
1. the solid dispersion composition of levocarnitine and sugar alcohols material, described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, and sugar alcohols material and levocarnitine are (13 ~ 50) with weight ratio: the ratio combination of 1, preferred sugar alcohols material and levocarnitine are (25 ~ 35) with weight ratio: the ratio combination of 1, described levocarnitine also comprises levocarnitine tartrate or levocarnitine hydrochlorate.
2. the preparation method of solid dispersion composition according to claim 1, it comprises:
Get levocarnitine or its salt and sugar alcohols material respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, dry, granulate, and obtain solid dispersion, wherein said described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, or
Levocarnitine or its salt are dissolved in ethanol or ethanol-water solution, this dissolution homogeneity is sprayed on sugar alcohols material, carry out wet granulation, soft material processed, granulate, dry, granulate, namely solid dispersion is obtained, wherein said described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, or
Get levocarnitine or its salt and sugar alcohols material, add solvent, in 20 DEG C under solvent boiling point temperature range, stirring makes levocarnitine or its salt and sugar alcohols substance dissolves or is scattered in solvent, from this mixture, desolventizing is removed after mix homogeneously, and it is dry and pulverize and obtain solid dispersion, wherein said described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, described solvent selected from ethanol, water or ethanol water,
In above-mentioned preparation, Rotary Evaporators can be taked to steam except desolventizing and dry method to remove, remove under reduced pressure, drying under reduced pressure, vacuum drying, lyophilization, spraying dry, fluid bed drying, one or more in heating, drying.
3. the solid dispersion of levocarnitine and sugar alcohols material and a solid dispersion composition for other pharmaceutical carrier, the pharmaceutical dosage form of described compositions is any pharmaceutical dosage form of acceptable on pharmaceutics, wherein said sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, and sugar alcohols material and levocarnitine are (13 ~ 50) with weight ratio: the ratio combination of 1, preferred sugar alcohols material and levocarnitine are (15 ~ 20) with weight ratio: the ratio combination of 1, described levocarnitine also comprises levocarnitine tartrate or levocarnitine hydrochlorate.
4. one kind contains the granule of the solid dispersion of levocarnitine and sugar alcohols material, described sugar alcohols material and levocarnitine are (13 ~ 50) with weight ratio: the ratio combination of 1, and preferred sugar alcohols material and levocarnitine are (25 ~ 35) with weight ratio: the ratio combination of 1, wherein said described sugar alcohols material comprises one or more compositions following: fructose, xylitol, polydextrose, oligofructose, mannitol, sucrose, glucose, resistant dextrin, Sorbitol, maltose, hydroxyl isomaltulose, Oligomeric manna sugar, dextrin, cyclodextrin, HP-β-CD, microcrystalline Cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose, pregelatinized Starch, starch, starch sugar, lactose, carboxymethyl starch sodium, protein sugar, sucralose, aspartame, acesulfame potassium, stachyose, neotame, steviol glycosides, described levocarnitine also comprises levocarnitine tartrate or levocarnitine hydrochlorate, and further, its preparation method comprises: sugar alcohols material is crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine is dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of sugar alcohols material and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product,
Or its preparation method comprises: get levocarnitine, sugar alcohols material, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
5. a granule for the solid dispersion of levocarnitine or its tartrate and sugar alcohols material, its recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 10%,
Polydextrose 25% ~ 55%,
Fructose or xylitol 45% ~ 65%;
Its preparation method comprises: polydextrose, fructose or xylitol are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of polydextrose and fructose or xylitol and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, polydextrose, fructose or xylitol respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
6. a granule for the solid dispersion of levocarnitine or its tartrate and sugar alcohols material, its recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 10%,
Oligofructose 25% ~ 55%,
Resistant dextrin 50% ~ 75%;
Its preparation method comprises: oligofructose, resistant dextrin are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of oligofructose and resistant dextrin and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, oligofructose and resistant dextrin respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
7. a granule for the solid dispersion of levocarnitine or its tartrate and sugar alcohols material, its recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 5% ~ 15%,
Oligomeric manna sugar 5% ~ 10%,
Sorbitol 50% ~ 75%;
Its preparation method comprises: Oligomeric manna sugar, Sorbitol are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of Oligomeric manna sugar and Sorbitol and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, Oligomeric manna sugar, Sorbitol respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
8. a granule for the solid dispersion of levocarnitine or its tartrate and sugar alcohols material, its recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 15%,
Hydroxyl isomaltulose 75% ~ 95%,
Carboxymethyl starch sodium 3% ~ 10%;
Its preparation method comprises: hydroxyl isomaltulose, carboxymethyl starch sodium are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of hydroxyl isomaltulose and carboxymethyl starch sodium and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, hydroxyl isomaltulose, carboxymethyl starch sodium respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
9. a granule for the solid dispersion of levocarnitine or its tartrate and sugar alcohols material, its recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 15%,
Sucrose or glucose 75% ~ 95%,
Carboxymethyl starch sodium 2% ~ 8%,
Polyvinylpyrrolidone 1% ~ 5%;
Its preparation method comprises: by sucrose or glucose, carboxymethyl starch sodium, polyvinylpyrrolidone mistake 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of sucrose or glucose, carboxymethyl starch sodium and polyvinylpyrrolidone and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or, its preparation method comprises: get levocarnitine or its tartrate, sucrose or glucose, carboxymethyl starch sodium, polyvinylpyrrolidone respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
10. a granule for the solid dispersion of levocarnitine or its tartrate and sugar alcohols material, its recipe quantity by weight percentage, contains:
Levocarnitine or its tartrate 2% ~ 15%,
Mannitol 35% ~ 65%,
Lactose 25% ~ 55%;
Its preparation method comprises: mannitol, lactose are crossed 80 mesh sieves respectively, preferred mistake 100 order, after taking by recipe quantity, mix homogeneously, separately levocarnitine or its tartrate are dissolved in 75% alcoholic solution, this dissolution homogeneity is sprayed in the mixture of mannitol and lactose and makes soft material, wet granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product;
Or its preparation method comprises: get levocarnitine or its tartrate, mannitol, lactose respectively, pulverized 80 mesh sieves respectively, preferred mistake 100 mesh sieve, according to equal increments mix homogeneously, or dry granulation, 45 ~ 70 DEG C of dryings, granulate, pack, sealing, to obtain final product.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108125916A (en) * | 2016-12-01 | 2018-06-08 | 江苏天士力帝益药业有限公司 | A kind of silaenafil dripping pill |
| CN116602915A (en) * | 2023-03-22 | 2023-08-18 | 哈尔滨誉衡制药有限公司 | Levocarnitine injection and preparation method thereof |
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| WO2004060353A1 (en) * | 2002-12-19 | 2004-07-22 | Pharmacia Corporation | Solid dispersions comprising a hygroscopic and/or deliquescent drug |
| CN1679533A (en) * | 2004-08-31 | 2005-10-12 | 北京正大绿洲医药科技有限公司 | Levo carnitine dropping pill and preparation thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004060353A1 (en) * | 2002-12-19 | 2004-07-22 | Pharmacia Corporation | Solid dispersions comprising a hygroscopic and/or deliquescent drug |
| CN1679533A (en) * | 2004-08-31 | 2005-10-12 | 北京正大绿洲医药科技有限公司 | Levo carnitine dropping pill and preparation thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108125916A (en) * | 2016-12-01 | 2018-06-08 | 江苏天士力帝益药业有限公司 | A kind of silaenafil dripping pill |
| CN108125916B (en) * | 2016-12-01 | 2021-11-30 | 江苏天士力帝益药业有限公司 | Sildenafil dropping pill |
| CN116602915A (en) * | 2023-03-22 | 2023-08-18 | 哈尔滨誉衡制药有限公司 | Levocarnitine injection and preparation method thereof |
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