CN103405381B - A kind of method of preparing unformed shape material - Google Patents
A kind of method of preparing unformed shape material Download PDFInfo
- Publication number
- CN103405381B CN103405381B CN201310373727.XA CN201310373727A CN103405381B CN 103405381 B CN103405381 B CN 103405381B CN 201310373727 A CN201310373727 A CN 201310373727A CN 103405381 B CN103405381 B CN 103405381B
- Authority
- CN
- China
- Prior art keywords
- aqueous solution
- state
- unformed
- hyaluronic acid
- derivatives
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to chemical field, disclose a kind of method of preparing unformed shape material. The method of the invention is by providing the homogeneous aqueous solution of this material and hyaluronic acid or its salt or derivatives thereof, and it is insoluble state that change condition makes this Substance Transformation, filters to obtain precipitation, the dry unformed shape material that is of washing. The method of the invention is simple and easy to do, and applicability is wide, has a good application prospect.
Description
Technical field
The present invention relates to chemical field, particularly a kind of method of preparing unformed shape material.
Background technology
The existence of solid drugs is an important content in drug research. Because solid drugs is without fixedType state often has absorbent properties in good In Vitro Dissolution and body, and may reach better clinical efficacy,Therefore, correlative study more and more comes into one's own. Unformed is a kind of special material crystal formation, and medicine is in nothingUnder sizing state, its various physicochemical properties and clinical pharmacodynamic properties are often different from general crystal formation medicine. CauseThis, in the polymorphous research of solid drugs, it is special that the further investigated of unformed material state is hadMeaning.
At present, mainly contain 3 kinds of viewpoints and explain the continuous differentiation between pure unformed state and pure crystalline state: 1.The crystalline particle of crystalline state material is decreased to atomic level (1～100nm) as seen gradually from naked eyes; 2. crystalline stateThe local lattice defect of material or distortion, along with the ratio in defect or distortion district increases, degree of crystallinity continues to reduce,Thereby " decrystallization " gradually, finally becomes the material of unformed state; 3. two states model: same solid grainSon is both containing pure crystalline state district, and again containing pure unformed shape district, the size of two kinds of region proportions determines solidsThe existence of matter. In the time of crystalline state material generation crystal transfer, the unformed state of upper state may be itIntermediateness.
The unformed state of solid drugs is not single form. Saying of broad sense, due to preparation method or storageDeposit the difference of mode, it is complete that a kind of solid matter can obtain physics, thermodynamics and kinetic propertyThe material of the unformed state of different two or more, the unformed state that these are different, is calledUnformed polymorphic.
At some in particular cases, unformed state more likely becomes advantage drug crystal forms. Unformed shapeThe solid drugs of state often has higher dissolution rate than stable crystalline state material, and therefore, preparation is without fixedThe insoluble drug of type state, oral administration biaavailability, the shortening onset time that may improve medicine.In new drug development, the selection to unformed solid matter state and further investigation have important science meaningJustice and practical value.
According to existing bibliographical information, the unformed state of solid drugs has better suction than other crystalline formReceiving character is very general phenomenon, and clinical this conventional class medicine is as nifedipine, carbamazepine etc.The compound of existing chemical synthesis in these medicines, has again the natural products that derives from Chinese herbal medicine. TheyCommon feature is low, the absorption difference of solubility under general crystal formation state, thus the performance affecting the treatment.
Why faster, better the absorption of the solid drugs of unformed state is, the physical chemistry special with itCharacter has close association. Because the per surface free energy of unformed shape material is larger, at solid pharmaceutical preparationIn the suspension forming after disintegration, the easy aquation of particle surface, the deflocculation of thicker hydration shell is better thanCrystalline state material, therefore, unformed drug particle more easily disperses, thereby has improved dissolution rate. UnformedThe medicine of state is the characteristic of stripping rapidly, makes again them compared with crystalline state medicine, at organism stomach and intestineLiquid Chinese traditional medicine relative concentration is higher, is easy to be absorbed, and on pharmacokinetic parameter, shows as CmaxHigher. In addition, if there is not crystal transfer in the medicine of unformed state in small intestine, or crystal transferSpeed slower, just can there is not rapid precipitation, drug concentration can be in a long time higher than stable state crystal formationThe concentration that can reach, thus the absorption total amount of medicine improves, and shows as area under the drug-time curve (AUC)Increase.
Owing to must reaching in vivo certain concentration ability onset after drug administration, therefore, blood concentrationRaising and the prolongation of valid density duration may affect drug effect. Research in recent years shows,The physical aspect of medicine may affect its action effect really.
In scientific research and industrial production, conventional two kinds of methods obtain the medicine of unformed state. A kind ofBe direct method, i.e. the methods such as, grinding dry by quenching, spraying are prepared the bulk drug of unformed state.Another kind is by special process, and bulk drug and suitable auxiliary material are processed into containing unformed shape medicine simultaneouslyPreparation.
Summary of the invention
Goal of the invention of the present invention, for a kind of method of preparing unformed shape material is provided, is particularly useful for the utmost pointProperty large, water in solubility rely on the preparation of the unformed solid of the material of pH value.
The method of preparing unformed shape material provided by the invention, provides this material and hyaluronic acid or its saltThe homogeneous aqueous solution of or derivatives thereof, it is insoluble state that change condition makes this Substance Transformation, filters to obtain precipitation,The dry unformed shape material that is of washing. This material and hyaluronic acid or its salt or its of providing of the present inventionThe homogeneous aqueous solution of derivative can be the aqueous solution by this material is provided, and adds hyaluronic acid or its saltOr derivatives thereof mixes; Or material to be prepared is joined in the hyaluronic aqueous solution and mixed.
Hyaluronic acid is a kind of high molecular polymer, is present between tissue, in the synovia of ball and socket joint and eyeballIn the interior nature of glass, the effect of play bonding, lubricating and protecting, basic structure is by the D-of disaccharide unitSenior polysaccharide, D-Glucose aldehydic acid and the N-acetyl glucose of glucuronic acid and N-acetyl-glucosamine compositionBetween amine, by β-1,3-glycosidic inkage is connected, and between disaccharide unit, is connected by β-Isosorbide-5-Nitrae-glycosidic inkage, and disaccharide unit canReach 25000 more than. Hyaluronic molecular weight from 5,000 to 2,000 ten thousand dalton not etc., are not white in bodyUnformed solid, odorless, tasteless, has hygroscopicity. Water-soluble, be insoluble to organic solvent. The ratio of the aqueous solutionCurl is-70 °～-80 °. Have higher viscosity property, the viscosity of its solution in pH value below or above 7Can there is irreversible decline.
The principle of the invention is in the aqueous solution of material to be prepared and hyaluronic acid or its salt or derivatives thereof,Hyaluronic acid or its salt or derivatives thereof form unordered network structure, make to want the material of crystallization to form microcosmicLack of alignment, thus unformed material obtained.
In the specific embodiment of the present invention, according in the different pH value aqueous solution of material to be preparedDifferent solubilities, by adding the pH value of regulator solution after hyaluronic acid to make species precipitate to be prepared out,Obtain unformed solid, the hyaluronic acid after using uses alcohol to purify, and can reuse. In this process,If the light of material to be prepared, heat, oxygen are unstable, should do lucifuge, low temperature, starvation etc. and locateReason.
Especially, as described in material be dissolved in acidic aqueous solution, regulate pH value to make this thing by alkaline matterMatter is converted into insoluble state. In the specific embodiment of the present invention, Cefditoren pivoxil Cephalosporins is dissolved in transparentThe acidic aqueous solution of matter acid, adds alkali neutralization, and filtering-depositing obtains the unformed powder of Cefditoren pivoxil Cephalosporins.
Especially, as described in material be dissolved in alkaline aqueous solution, regulate pH value to make this thing by acidic materialsMatter is converted into insoluble state. In the specific embodiment of the present invention, cefotaxime acid is dissolved in to hyalomitomeThe alkaline aqueous solution of acid, acid neutralization, filtering-depositing obtains the unformed powder of cefotaxime acid.
Especially, as described in material be insoluble to certain organic solvent, by adding this organic solvent to make this thingMatter is converted into insoluble state. In the specific embodiment of the present invention, Ceftriaxone Sodium is dissolved in to hyalomitomeAqueous acid, adds acetone filtering-depositing and obtains the unformed powder of Ceftriaxone Sodium.
As preferably, described hyaluronate is Sodium Hyaluronate, calcium hyauronate or zinc hyaluronate.
As preferably, to be hyaluronic acid form by esterification, crosslinked, grafting described derivatives of hyaluronic acidsOr hyaluronic acid metal complex.
As preferably, in the aqueous solution of described material, solute mass percent is 5%-15%.
As preferably, the addition of described hyaluronic acid or its salt or derivatives thereof is for making its mass percentFor 1%-5%.
As preferably, described washing is the hyaluronic acid aqueous solution washing with mass percent 1%-5%.
The method of preparing unformed shape material provided by the invention, simple and easy to do, applicability is wide, especially suitableThe preparation large for polarity, water solubility relies on the unformed solid of the material of pH value, as antibioticIn cephalo-type, PCs, adriamycin class etc. and the preparation of other common drugs, have good shouldUse prospect.
Detailed description of the invention
The invention discloses a kind of method of preparing unformed shape material, those skilled in the art can use for referenceContent herein, suitably improves technological parameter and realizes. Special needs to be pointed out is, all similar replacements andChange apparent to those skilled in the artly, they are all deemed to be included in the present invention. ThisThe method of invention and application are described by preferred embodiment, and related personnel obviously can be not de-In content of the present invention, spirit and scope, methods and applications as herein described are changed or suitably changedWith combination, realize and apply the technology of the present invention.
In order to make those skilled in the art understand better technical scheme of the present invention, below in conjunction with specificallyThe present invention is described in further detail for embodiment.
Embodiment 1:
The Ceftriaxone Sodium being dissolvable in water in the aqueous solution is dissolved in water, adds the hyalomitome of 1%-5%Acid, then slowly adds acetone, while making the percentage by volume of acetone in solution be 50-80%, stops, and filtersPrecipitation, cleans three times with the aqueous acetone solution of 50%-80%, dry, the solid that obtains material to be prepared withoutSizing. Measure and determine that it is unformed powder with powder X-ray RD.
Embodiment 2:
Get Cefditoren pivoxil Cephalosporins bulk drug 10g, be dissolved in 100mL1N hydrochloric acid solution (containing 2% hyalomitomeAcid sodium), slowly drip 1N NaOH 100ml and neutralize, whole process is 5 DEG C of lucifuge, temperature controlsUnder following condition, carry out, last filtering-depositing, with 2% aqueous solution of sodium hyaluronate 30ml cleaning three times,40 DEG C are drying to obtain unformed Cefditoren pivoxil Cephalosporins, and powder X-ray RD measures and determines that it is unformed powder.
Embodiment 3:
The cefotaxime acid being dissolvable in water in alkaline aqueous solution is dissolved in alkaline aqueous solution, addsThe hyaluronic acid of 1%-5%, then slowly adds hydrochloric acid neutralization (speed is about 1.2-2.1ml/min), filtersPrecipitation, uses the hyaluronic acid aqueous solution of 1%-5% to clean three times, dry, obtains the solid of material to be preparedUnformed, powder X-ray RD measures and determines that it is unformed powder.
The above is only the preferred embodiment of the present invention, it should be pointed out that general for the artLogical technical staff, under the premise without departing from the principles of the invention, can also make some improvement and profitDecorations, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (1)
1. a method of preparing unformed shape material, is characterized in that, this material and transparent is providedThe homogeneous aqueous solution of matter acid or its salt or derivatives thereof, it is insoluble shape that change condition makes this Substance TransformationState, filters to obtain precipitation, the dry unformed shape material that is of washing;
Described material is dissolved in acidic aqueous solution, regulates pH value to make this Substance Transformation be by alkaline matterInsoluble state;
Described material is dissolved in alkaline aqueous solution, regulates pH value to make this Substance Transformation be by acidic materialsInsoluble state; Or
Described material is insoluble to organic solvent, by adding this organic solvent to make this Substance Transformation for notMolten state;
Described hyaluronate is Sodium Hyaluronate, calcium hyauronate, zinc hyaluronate;
To be hyaluronic acid form or its gold by esterification, crosslinked, grafting described derivatives of hyaluronic acidsMetal complex;
In the aqueous solution of described material, solute mass percent is 5%-15%;
The addition of described hyaluronic acid or its salt or derivatives thereof is for making its mass percent be1％-5％；
Described washing is the hyaluronic acid aqueous solution washing with mass percent 1%-5%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310373727.XA CN103405381B (en) | 2013-08-23 | 2013-08-23 | A kind of method of preparing unformed shape material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310373727.XA CN103405381B (en) | 2013-08-23 | 2013-08-23 | A kind of method of preparing unformed shape material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103405381A CN103405381A (en) | 2013-11-27 |
| CN103405381B true CN103405381B (en) | 2016-05-25 |
Family
ID=49598457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310373727.XA Active CN103405381B (en) | 2013-08-23 | 2013-08-23 | A kind of method of preparing unformed shape material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103405381B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1684673A (en) * | 2002-08-07 | 2005-10-19 | 史密丝克莱恩比彻姆公司 | Electrospun amorphous pharmaceutical compositions |
-
2013
- 2013-08-23 CN CN201310373727.XA patent/CN103405381B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1684673A (en) * | 2002-08-07 | 2005-10-19 | 史密丝克莱恩比彻姆公司 | Electrospun amorphous pharmaceutical compositions |
Non-Patent Citations (2)
| Title |
|---|
| "反应沉淀法制备阿齐霉素药物超微粉体";王国联等;《过程工程学报》;20070831;第7卷(第4期);第802-803页第2.2.1部分，第805页左列第1段 * |
| "固体药物无定型状态的研究进展";应剑等;《药学学报》;20090512;第44卷(第5期);第446页右列最后1段-第447页左列第1段 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103405381A (en) | 2013-11-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Cunha et al. | Sulfated seaweed polysaccharides as multifunctional materials in drug delivery applications | |
| CN104530263B (en) | A kind of preparation method of gallic acid bagasse xylan ester | |
| WO2010087207A1 (en) | Low-molecular polysulfated hyaluronic acid derivative and medicine containing same | |
| CN103041377B (en) | Preparation method of lysozyme loaded chitosan/gamma polyglutamic acid composite nanoparticles | |
| CN100451023C (en) | Levo-ornidazole phosphate, preparing process and use thereof | |
| Chen et al. | Preparation and characterization of nanostarch-based green hard capsules reinforced by cellulose nanocrystals | |
| CN106432538A (en) | Method for preparing chitin oligosaccharides, chitooligosaccharides and chitosan oligosaccharides | |
| CN104644547B (en) | A kind of long-acting cefotaxime sodium injection and preparation method thereof | |
| CN101229122B (en) | Zanamivir nasal in situ jellies with phase variation property and preparing method thereof | |
| JP6052183B2 (en) | Gel of reduced pyrroloquinoline quinone | |
| CN104873467A (en) | Preparation method of biodegradable interpenetrating network polymer microspheres | |
| CN103405381B (en) | A kind of method of preparing unformed shape material | |
| CN108003252B (en) | Enteromorpha polysaccharide carboxymethylation modified product with improved antioxidant activity and preparation method thereof | |
| CN105919978A (en) | Preparation method of amoxicillin microsphere slow-release capsule | |
| CN109721740A (en) | A method of continuously preparing the chitin/chitosan solution of different deacetylations | |
| CN102670490A (en) | Itraconazole oral solution and preparation method thereof | |
| CN101942040B (en) | Method for removing oversulfated chondroitin sulfate in heparin sodium | |
| CN109136307B (en) | Method for preparing chitosan oligosaccharide by using helicase and application thereof | |
| CN107088201A (en) | It is a kind of to be used to treat composition of gout and its production and use | |
| CN102276445B (en) | Colloidal bismuth tartrate compound, medicaments thereof, preparation method thereof and application thereof | |
| CN104000778A (en) | Ribavirin injection and preparing method thereof | |
| CN110772498A (en) | Preparation method of novel fucoxanthin-loaded fucoidan sulfate nanoparticles | |
| CN102552153A (en) | Orally-taken tuckahoe polysaccharide sulfate-chitosan nanoparticle and preparation method thereof | |
| CN102886062A (en) | Iodinated chitosan biological antibacterial gel | |
| CN107019705B (en) | Application of carboxymethyl chitosan in preparing product for improving immunity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |