CN110464712A - A kind of water-soluble pharmaceutical compositions and preparation method thereof - Google Patents
A kind of water-soluble pharmaceutical compositions and preparation method thereof Download PDFInfo
- Publication number
- CN110464712A CN110464712A CN201910820864.0A CN201910820864A CN110464712A CN 110464712 A CN110464712 A CN 110464712A CN 201910820864 A CN201910820864 A CN 201910820864A CN 110464712 A CN110464712 A CN 110464712A
- Authority
- CN
- China
- Prior art keywords
- water
- pharmaceutical compositions
- soluble pharmaceutical
- structural material
- soluble
- 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.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G12/00—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen
- C08G12/02—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes
- C08G12/04—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes with acyclic or carbocyclic compounds
- C08G12/06—Amines
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
The invention discloses a kind of water-soluble pharmaceutical compositions and preparation method thereof, are related to pharmaceutical technology field.The water-soluble pharmaceutical compositions are nucleocapsid structure；Wherein, the quality of the core is less than the quality of the shell；The core is water soluble drug；The shell, as mass fraction, including 60%~98% cross-linked polymer；2%~50% antiplastering aid；The cross-linked polymer is that amino-contained structural material and structural material containing aldehyde radical carry out cross-linking reaction and obtain.The present invention with aldehyde radical structural material by react forming cross-linked polymer amino structure substance, the composition with core-shell structure can be formed with water soluble drug, and under the action of antiplastering aid, it can make the composition of core-shell structure that there is dispersibility well, be not easy to bond.
Description
Technical field
The present invention relates to pharmaceutical technology fields more particularly to a kind of water-soluble pharmaceutical compositions and preparation method thereof.
Background technique
In recent years, characterized by unique mode controls release (sustained release), isolation active constituent, covers and hide, reduce toxicity etc.
Encapsulation techniques had been more and more widely used in the fields such as food, daily use chemicals, medicine, agricultural.
Encapsulation techniques mainly based on microdisplay package, that is, microcapsules technology, refer to and active component are wrapped in certain table
In the micro-capsule of face characteristic, when in use, according to the principle of slow releasing function, by the rate of active component as expected gradually from micro-capsule
It releases.From a technical point of view, encapsulation techniques realization need to satisfy two conditions:: active component allows for being wrapped up
In micro-capsule；Micro-capsule as transportation media has suitable property to ensure to wrap in active component wherein in expected condition
Under can discharge.
Currently, microcapsules technology field is mostly to wrap up based on the substances such as hydrophobic liquid (such as essence), and the relevant technologies
Comparative maturity；And coated water-soluble solid is especially highly soluble in the research of the active solid and aqueous solution of water relatively very
It is few.And mostly water soluble drug such as Cetylpyridinium Chloride biology, medicine and other fields application mostly based on micro direct addition, lack
The persistence of the slow release of drug, antibacterial is poor, if can will such similar water-soluble active solid microencapsulation, not only can be with
Increase its sustained release performance, also expands its application range, improvement effect to a certain extent.
Summary of the invention
The technical problem to be solved by the present invention is to as mentioned in the background the problem of, and provide a kind of water-soluble pesticide
Compositions and preparation method thereof.
To solve the above-mentioned problems, the present invention proposes following technical scheme:
In a first aspect, the present invention provides a kind of water-soluble pharmaceutical compositions, the water-soluble pharmaceutical compositions are core-shell structure copolymer knot
Structure；Wherein, the quality of the core is less than the quality of the shell；The core is water soluble drug；
The shell, as mass fraction, including following component:
60%~98% cross-linked polymer；
2%~50% antiplastering aid；
The cross-linked polymer is that amino-contained structural material and structural material containing aldehyde radical carry out cross-linking reaction and obtain.
Further, the water soluble drug is at 25 DEG C, and medicinal mixture of the solubility greater than 0.1g, drug extract
Object powder or drug extract solution.
Further, the amino-contained structural material is the molecule containing primary amine or secondary amine or polymerization on molecular structure
Object.
Further, the amino-contained structural material is ethylenediamine, phenylenediamine, diethylenetriamine, triethylene tetramine, tetrem
Five amine of base, hexamethylene diamine, polyethyleneimine, polyetheramine, chitosan it is one or more.
Further, the structural material containing aldehyde radical is the monoaldehyde containing aldehyde radical, dialdehyde on molecular structure.
Further, the structural material containing aldehyde radical be carbon atom number be 1~18 fatty aldehyde, vanillic aldehyde, benzaldehyde, third
Dialdehyde, butanedial, glutaraldehyde, hexandial.
Further, the antiplastering aid is divalent metal fatty acid salt.
Further, the antiplastering aid is fatty acid magnesium, fatty calcium.
Further, the shell can also include emulsifier.
Second aspect, the present invention also provides the preparation methods of water-soluble pharmaceutical compositions as described in relation to the first aspect, including
Following step:
1) in proportion, the aqueous solution of water soluble drug and amino-contained structural material is carried out to emulsification point under nonpolar solvent
It dissipates, obtains emulsification system；
2) antiplastering aid is added in the emulsification system of step 1)；
3) structural material containing aldehyde radical is added in step 2), heating carries out cross-linking reaction；
4) it after reaction, is washed respectively with petroleum ether and isopropanol, separation is combined to get to water soluble drug
Object.
Compared with prior art, the attainable technical effect of present invention institute includes:
It, can be with water-soluble pesticide by react forming cross-linked polymer amino structure substance with aldehyde radical structural material
Object forms the composition with core-shell structure, and under the action of antiplastering aid, and the composition of core-shell structure can be made to have very
Good dispersibility, is not easy to bond.
Detailed description of the invention
Technical solution in order to illustrate the embodiments of the present invention more clearly, below will be to needed in embodiment description
Attached drawing is briefly described, it should be apparent that, drawings in the following description are some embodiments of the invention, general for this field
For logical technical staff, without creative efforts, it is also possible to obtain other drawings based on these drawings.
Fig. 1 is the sample microscope shape appearance figure of embodiment 1.
Fig. 2 is the sample microscope shape appearance figure of embodiment 2.
Fig. 3 is the sample microscope shape appearance figure of embodiment 3.
Fig. 4 is the sample microscope shape appearance figure of embodiment 4.
Fig. 5 is the sample microscope shape appearance figure of comparative example 1.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, is clearly and completely retouched to the technical solution in embodiment
It states, similar reference numerals represent similar component in attached drawing.Obviously, will be described below embodiment is only the present invention one
Divide embodiment, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art are not making
Every other embodiment obtained, shall fall within the protection scope of the present invention under the premise of creative work.
It should be appreciated that ought use in this specification and in the appended claims, term " includes " and "comprising" instruction
Described feature, entirety, step, operation, the presence of element and/or component, but one or more of the other feature, whole is not precluded
Body, step, operation, the presence or addition of element, component and/or its set.
It is also understood that in this embodiment of the present invention term used in the description merely for the sake of description particular implementation
Example purpose and be not intended to limit the embodiment of the present invention.Such as the institute in specification and appended book of the embodiment of the present invention
As use, other situations unless the context is clearly specified, otherwise " one " of singular, "one" and "the" are intended to wrap
Include plural form.
The embodiment of the present invention provides a kind of water-soluble pharmaceutical compositions, and the water-soluble pharmaceutical compositions are nucleocapsid structure；
Wherein, the quality of the core is less than the quality of the shell；The core is water soluble drug；The shell, as mass fraction, including
Following component:
60%~98% cross-linked polymer；
2%~50% antiplastering aid；
The cross-linked polymer is that amino-contained structural material and structural material containing aldehyde radical carry out cross-linking reaction and obtain.
Preferably, in other embodiments, the shell, including it is 80%~95% cross-linked polymer, 2%~20% anti-stick
Agent.
Preferably, in other embodiments, the shell, including it is 80%~95% cross-linked polymer, 2%~20% anti-stick
Agent.
In other embodiments, the water soluble drug is at 25 DEG C, and drug of the solubility greater than 0.1g, drug extract
Object powder or drug extract solution.
It is appreciated that the present invention does not limit the specific substance of water soluble drug, can be honeysuckle extract solution,
The medicinal mixture of Cetylpyridinium Chloride aqueous solution or other active effects.
In specific implementation, the amino-contained structural material is the molecule containing primary amine or secondary amine or poly- on molecular structure
Close object.
In specific implementation, the amino-contained structural material is ethylenediamine, phenylenediamine, diethylenetriamine, triethylene tetramine, four
Five amine of ethyl, hexamethylene diamine, polyethyleneimine, polyetheramine, chitosan it is one or more.
In specific implementation, the structural material containing aldehyde radical is the monoaldehyde containing aldehyde radical, dialdehyde on molecular structure.
In specific implementation, the structural material containing aldehyde radical be carbon atom number be 1~18 fatty aldehyde, vanillic aldehyde, benzaldehyde,
Malonaldehyde, butanedial, glutaraldehyde, hexandial.
In specific implementation, the antiplastering aid is divalent metal fatty acid salt.
In specific implementation, the antiplastering aid is fatty acid magnesium, fatty calcium.
In specific implementation, the shell can also include emulsifier.
The present invention also provides the preparation methods of above-mentioned water-soluble pharmaceutical compositions, include the following steps:
1) in proportion, the aqueous solution of water soluble drug and amino-contained structural material is carried out to emulsification point under nonpolar solvent
It dissipates, obtains emulsification system；
2) antiplastering aid is added in the emulsification system of step 1)；
3) structural material containing aldehyde radical is added in step 2), heating is reacted；
4) it after reaction, is washed respectively with petroleum ether and isopropanol, separation is combined to get to water soluble drug
Object.
Embodiment 1
A kind of preparation method of water-soluble pharmaceutical compositions, including processing step below:
By Cetylpyridinium Chloride aqueous solution 10g, the mixed aqueous solution 20g containing the poly- ethyleneimine of 5g and 5g diethylenetriamine, it is added
Into the atoleine containing 2g Arlacel-80, stirring and emulsifying；2g magnesium stearate is added；12g glutaraldehyde is added；60 DEG C are warming up to,
It is stirred to react 6h；It is washed twice, is centrifugated with petroleum ether and isopropanol respectively, it is dry, obtain water-soluble pharmaceutical compositions.
Embodiment 2
A kind of preparation method of water-soluble pharmaceutical compositions, including processing step below:
Cetylpyridinium Chloride aqueous solution 10g, the aqueous solution 20g containing the poly- ethyleneimine of 10g are added to containing 5g Arlacel-80
In atoleine, stirring and emulsifying；5g magnesium stearate is added；12g glutaraldehyde is added；60 DEG C are warming up to, 6h is stirred to react；It uses respectively
Petroleum ether and isopropanol wash twice, and are centrifugated, dry, obtain water-soluble pharmaceutical compositions.
Embodiment 3
A kind of preparation method of water-soluble pharmaceutical compositions, including processing step below:
By Flos Lonicerae extractive solution 10g, the aqueous solution 50g containing 10g chitosan, it is added to the liquid containing 5g Arlacel-80
In paraffin, stirring and emulsifying；8g magnesium stearate is added；10g vanillic aldehyde is added；60 DEG C are warming up to, 6h is stirred to react；Petroleum is used respectively
Ether and isopropanol wash twice, and are centrifugated, dry, obtain water-soluble pharmaceutical compositions.
Embodiment 4
A kind of preparation method of water-soluble pharmaceutical compositions, including processing step below:
Honeysuckle is extracted into solution 10g, the mixed aqueous solution 10g containing the poly- ethyleneimine of 2g and 2g polyetheramine, is added to and contains
In the atoleine for having 2g Arlacel-80, stirring and emulsifying；2g calcium stearate is added；12g palmital is added；60 DEG C are warming up to, stirring
React 6h；It is washed twice, is centrifugated with petroleum ether and isopropanol respectively, it is dry, obtain water-soluble pharmaceutical compositions.
Comparative example 1
A kind of preparation method of pharmaceutical composition, including processing step below:
By Cetylpyridinium Chloride aqueous solution 10g, the mixed aqueous solution 20g containing the poly- ethyleneimine of 5g and 5g diethylenetriamine, it is added
In atoleine containing 2g Arlacel-80, stirring and emulsifying；12g glutaraldehyde is added；60 DEG C are warming up to, 6h is stirred to react；It uses respectively
Petroleum ether and isopropanol wash twice, and are centrifugated, dry, obtain water-soluble pharmaceutical compositions.
By pharmaceutical composition made from water-soluble pharmaceutical compositions made from embodiment 1-4 and comparative example 1 in microscope
It is observed, the results are shown in Table 1 for the dispersibility of each composition.
The dispersed result of 1. different components sample of table
| Sample | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Comparative example 1 |
| Dispersibility | Uniformly | Uniformly | Uniformly | Uniformly | Reunite |
It can see from the microscopy images of table 1 and Fig. 1~5, the water soluble drug combination of the embodiment of the present invention 1~4
Object is the uniform round little particle of dispersibility, and agglomeration is then presented in the pharmaceutical composition of comparative example 1.
In the above-described embodiments, it all emphasizes particularly on different fields to the description of each embodiment, is not described in some embodiment
Part, reference can be made to the related descriptions of other embodiments.
The above is a specific embodiment of the invention, but scope of protection of the present invention is not limited thereto, any ripe
It knows those skilled in the art in the technical scope disclosed by the present invention, various equivalent modifications can be readily occurred in or replaces
It changes, these modifications or substitutions should be covered by the protection scope of the present invention.Therefore, protection scope of the present invention should be with right
It is required that protection scope subject to.
Claims (10)
1. a kind of water-soluble pharmaceutical compositions, which is characterized in that the water-soluble pharmaceutical compositions are nucleocapsid structure；Wherein, institute
The quality for stating core is less than the quality of the shell；The core is water soluble drug；
The shell, as mass fraction, including following component:
60%~98% cross-linked polymer；
2%~50% antiplastering aid；
The cross-linked polymer is that amino-contained structural material and structural material containing aldehyde radical carry out cross-linking reaction and obtain.
2. water-soluble pharmaceutical compositions as described in claim 1, which is characterized in that the water soluble drug be at 25 DEG C,
Solubility is greater than medicinal mixture, drug extract powder or the drug extract solution of 0.1g.
3. water-soluble pharmaceutical compositions as described in claim 1, which is characterized in that the amino-contained structural material is molecule knot
Molecule or polymer containing primary amine or secondary amine on structure.
4. water-soluble pharmaceutical compositions as claimed in claim 3, which is characterized in that the amino-contained structural material is second two
Amine, phenylenediamine, diethylenetriamine, triethylene tetramine, tetraethylenepentamine, hexamethylene diamine, polyethyleneimine, polyetheramine, shell
Glycan it is one or more.
5. water-soluble pharmaceutical compositions as described in claim 1, which is characterized in that the structural material containing aldehyde radical is molecule knot
Monoaldehyde, dialdehyde on structure containing aldehyde radical.
6. water-soluble pharmaceutical compositions as claimed in claim 5, which is characterized in that the structural material containing aldehyde radical is carbon atom
Fatty aldehyde, vanillic aldehyde of the number for 1~18, benzaldehyde, malonaldehyde, butanedial, glutaraldehyde, hexandial.
7. water-soluble pharmaceutical compositions as described in claim 1, which is characterized in that the antiplastering aid is divalent metal fatty acid
Salt.
8. water-soluble pharmaceutical compositions as claimed in claim 7, which is characterized in that the antiplastering aid is fatty acid magnesium, fat
Calcium.
9. water-soluble pharmaceutical compositions as described in claim 1, which is characterized in that the shell can also include emulsifier.
10. the preparation method of water-soluble pharmaceutical compositions as described in any one of claims 1 to 9, which is characterized in that including with
Under step:
1) aqueous solution of water soluble drug and amino-contained structural material in proportion, is subjected to emulsion dispersion under nonpolar solvent,
Obtain emulsification system；
2) antiplastering aid is added in the emulsification system of step 1)；
3) structural material containing aldehyde radical is added in step 2), heating carries out cross-linking reaction；
4) it after reaction, is washed, is separated to get water-soluble pharmaceutical compositions are arrived respectively with petroleum ether and isopropanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910820864.0A CN110464712A (en) | 2019-08-30 | 2019-08-30 | A kind of water-soluble pharmaceutical compositions and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910820864.0A CN110464712A (en) | 2019-08-30 | 2019-08-30 | A kind of water-soluble pharmaceutical compositions and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110464712A true CN110464712A (en) | 2019-11-19 |
Family
ID=68514522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910820864.0A Pending CN110464712A (en) | 2019-08-30 | 2019-08-30 | A kind of water-soluble pharmaceutical compositions and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110464712A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1565428A (en) * | 2003-07-08 | 2005-01-19 | 中国科学院过程工程研究所 | Chitosan microcapsule and its preparation method and uses |
| CN101940554B (en) * | 2010-09-03 | 2012-06-20 | 四川大学 | Multi-core adhesive microspheres for loading water soluble low molecular medicament and preparation method thereof |
| WO2017021983A1 (en) * | 2015-08-06 | 2017-02-09 | Rubicon Research Private Limited | Particulate delivery systems |
-
2019
- 2019-08-30 CN CN201910820864.0A patent/CN110464712A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1565428A (en) * | 2003-07-08 | 2005-01-19 | 中国科学院过程工程研究所 | Chitosan microcapsule and its preparation method and uses |
| CN101940554B (en) * | 2010-09-03 | 2012-06-20 | 四川大学 | Multi-core adhesive microspheres for loading water soluble low molecular medicament and preparation method thereof |
| WO2017021983A1 (en) * | 2015-08-06 | 2017-02-09 | Rubicon Research Private Limited | Particulate delivery systems |
Non-Patent Citations (3)
| Title |
|---|
| GUANG WANG ET AL: "Formulation of vanillin cross-linked chitosan nanoparticles and its characterization", 《ADVANCED MATERIALS RESEARCH VOLS》 * |
| QIN ZOU ET AL: "Preparation and characterization of vanillin-crosslinked chitosantherapeutic bioactive microcarriers", 《INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES》 * |
| 李俊峰等: "香草醛交联壳聚糖载药微球的性能及其成球机理分析", 《高等学校化学学报》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5051304A (en) | Microcapsules based on gelatin and polysaccharides and process for obtaining same | |
| US5132117A (en) | Aqueous core microcapsules and method for their preparation | |
| US6375968B1 (en) | Encapsulated active material immobilized in hydrogel microbeads | |
| AU2002340552B2 (en) | Active material immobilized in stable hydrogel microbeads | |
| CN101928641B (en) | Essence microcapsule with long-term effectiveness and preparation method thereof | |
| WO1993025302A1 (en) | Emulsifier, emulsifying composition and powdery composition | |
| JP2007534473A (en) | Oil encapsulation by coacervation | |
| AU2002340552A1 (en) | Active material immobilized in stable hydrogel microbeads | |
| CN100532438C (en) | Starch microspheres and method for preparing the same | |
| WO1996001103A1 (en) | Multiple encapsulation of oleophilic substances | |
| US3549555A (en) | Encapsulation of lipophilic liquid-in-hydrophilic liquid emulsions | |
| CN107486111B (en) | A kind of preparation method of multilayer embedding microcapsules | |
| EP0051161A1 (en) | Encapsulation by entrapment within starch adduct matrix | |
| Amelian et al. | Polymers in pharmaceutical taste masking applications | |
| JP2004509739A (en) | Immediate water-soluble capsule and method for producing the same | |
| EP0332175A2 (en) | Method of producing microcapsule | |
| JP2015057277A (en) | Microcapsule, solid material-including microcapsule, and manufacturing method thereof | |
| JP2851302B2 (en) | Manufacturing method of microcapsules containing water-soluble substance | |
| CN107029639B (en) | Slow-odor type polyelectrolyte microcapsule with casein-sodium alginate as composite wall material and preparation method thereof | |
| CN110464712A (en) | A kind of water-soluble pharmaceutical compositions and preparation method thereof | |
| TW200831180A (en) | Method for preventing crystallization | |
| KR101982288B1 (en) | Microcapsule for pH dependent release of natural antimicrobial extract and preparation method of the same | |
| CN109699687A (en) | A kind of preparation method of environment-friendly type pyrethrin control-release microsphere | |
| JP3235283B2 (en) | Method for producing spherical chitosan fine particles | |
| CN105746509A (en) | Nematicide microcapsule and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20191119 |
|
| RJ01 | Rejection of invention patent application after publication |