CN107320461A - A kind of preparation method based on diglyceride solid lipid nano granule - Google Patents
A kind of preparation method based on diglyceride solid lipid nano granule Download PDFInfo
- Publication number
- CN107320461A CN107320461A CN201710705668.XA CN201710705668A CN107320461A CN 107320461 A CN107320461 A CN 107320461A CN 201710705668 A CN201710705668 A CN 201710705668A CN 107320461 A CN107320461 A CN 107320461A
- Authority
- CN
- China
- Prior art keywords
- diglyceride
- solid lipid
- lipid nano
- nano granule
- preparation
- 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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
-
- 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
- A61K9/10—Dispersions; Emulsions
Abstract
The present invention relates to a kind of preparation method of novel solid lipid nano particle, it selects a kind of new functional grease --- and diglyceride is that lipid carrier prepares solid lipid nano granule, and the exploitation of efficient utilization and novel solid lipid nano particle carrier for diglyceride provides new approaches.It is characterized in that preparation flow is：A, weigh qs glycerin diester and be heated to temperature T and make it melt to form oil phase completely；B, weigh appropriate emulsifying agent and distilled water and be heated to temperature T-shaped into aqueous phase；C, mix oil phase and aqueous phase under the conditions of temperature T and form thick emulsion；D, the bright microemulsion of appropriate absolute ethyl alcohol formation clarification is added dropwise into thick emulsion；E, the microemulsion of heat is scattered in 2~10 DEG C of cold water formation solid lipid nano granule dispersion liquid by a certain percentage.This technical process is simple to operate, equipment is cheap, it is low to energy expenditure, with very strong practicality.
Description
Technical field
The present invention relates to biomedicine technical field, specifically, it is related to a kind of based on diglyceride solid lipid nano
Pharmaceutical carrier of grain and preparation method thereof.
Background technology
Solid lipid nano granule（solid lipid nanoparticles, SLN）It is to grow up 1990s
Delivery system of new generation, refer to the particle diameter formed by carrier using solid natural or the lipoid of synthesis 10~1000 nm's
Solid micelle delivery system.The lipid carrier that solid lipid nano granule is used has low toxicity, good biocompatibility, biology can
The characteristics of degraded, therefore have huge application value.
The lipid carrier of conventional solid lipid nano granule is three simple glycerides, monoglyceride, aliphatic acid etc., wherein with
Triglycerides is most commonly seen.But, with the raising of people's health consciousness, disease risk is more weighed caused by triglycerides
Depending on finding the replacement lipid of triglycerides has urgent researching value and application value；On the other hand, triglycerides, glycerine
The monoacid such as monoesters, aliphatic acid lipid formed solid lipid nano granule do not have lattice defect, easily occur Medicated Permeation and
The low phenomenon of drugloading rate.Therefore, using more health and safety, and the various lipid of fatty acid species is used as solid lipid nano granule
Carrier there is very important application value and Research Significance.
Diglyceride（Diacylglycerol, DAG）, it is with being obtained after a molecule glycerine esterification by two molecules of fatty acids
Structured lipid, it is different from the position that glycerol hydroxy groups are combined according to aliphatic acid, 1,3-DAG and 1,2- glycerine two can be divided into
Ester, wherein 1,3-DAG are more stablized.Diglyceride in terms of outward appearance, local flavor and nutritive value with triglycerides difference not
Greatly, metabolic way of both lipids in human body is caused in the presence of substantially poor yet with difference of the diglyceride in structure
It is different.Research finds that human body body weight and body fat content after lipid of the intake rich in diglyceride can be significantly reduced, meanwhile,
Diglyceride also has reducing blood lipid, prevents visceral fat accumulation, alleviates numerous physiological functions such as diabetes and its complication.This
Outside, diglyceride can easily introduce the aliphatic acid of two kinds of different structures, can be formed when solid lipid nano granule is formed
More lattice defects, and then there is more preferable embedding efficiency and entrapment stability to medicine.
The report based on diglyceride solid lipid nano granule is yet there are no, in consideration of it, we have invented based on more
The method that the diglyceride of health and safety prepares solid lipid nano granule as lipid carrier.
The content of the invention
In order to overcome the health problem and stability problem present in the lipid carrier of conventional solid lipid nano particle, we
Invent a kind of based on preparation method of the diglyceride for the solid lipid nano granule of lipid carrier.By the method, will can have
The diglyceride for having excellent physiological function is incorporated into the application of solid lipid nano granule.
The preparation method comprises the following steps：
A, weigh qs glycerin diester and be heated to design temperature T and make it melt to form oil phase or the breast by appropriate poorly water-soluble completely
Agent is thermally formed liquid oil phase with diglyceride；
B, weigh appropriate emulsifying agent and distilled water is mixed to form aqueous phase, and be heated to temperature T；
C, aqueous phase and oil phase are stirred under identical temperature T mixing form thick emulsion within 5~10 minutes；
D, appropriate absolute ethyl alcohol is added dropwise into thick emulsion until forming the bright microemulsion of clarification；
E, the microemulsion of heat is scattered in 2~10 DEG C of cold water formation solid lipid nano granule dispersion liquid by a certain percentage.
The heating-up temperature T of diglyceride is more than selected diglyceride fusing point 5~10 DEG C of temperature in step a.
Emulsifying agent is the compounding of ionic emulsifying agent and nonionic emulsifier, such as soybean lecithin, SDS in step b
The compounding of the nonionic emulsifier such as ionic emulsifying agent and polysorbas20, polysorbate60, Tween 80；But it is preferred that the small ovum of bio-toxicity
Phosphatide and tween.
Aqueous phase both can be all emulsifying agents or the good emulsifying agent of part aqueous in step b, according to compounding
Emulsifying agent in water dissolubility judge.The formation of aqueous phase can using include mechanical agitation, magnetic agitation, high shear dispersion,
The processing mode such as high-pressure homogeneous, ultrasonic.
The mass ratio of diglyceride and emulsifying agent is 1 in step a, b:3~1:8, and two class emulsifying agents are answered in emulsifying agent
Can be ionic with ratio：Non-ionic mass ratio is 1:3~1:49, the mass concentration of diglyceride is in whole system
1%~10%.
When aqueous phase and oil phase being mixed to form into thick emulsion in step c, aqueous phase should be added quickly while hot, to avoid liquid oil phase
By cold crystallization.Form the basis for estimation of thick emulsion：By sample slight wobble, observation wall built-up backflow emulsion is that color and luster is homogeneous, more
It is defined when bright.
The addition of absolute ethyl alcohol, which should be, in step d is added dropwise, and is preferably that band needle applicator is added dropwise, it is ensured that with
The form of fine drop is added.The basis for estimation of microemulsion formation：The homogeneous clarification of solution is bright.
The microemulsion of heat, which is dispersed in cold water, in step e can make the rapid crystallisation by cooling of liquid oil phase and form solid lipid
Nanoparticle dispersion liquid, hot microemulsion is 1 with cold scattered water volume ratio：5~1:25.Obtained solid lipid nano granule dispersion liquid can
Further freeze-drying obtains freeze-dried powder, as solid lipid nano granule.
On the preparation method based on diglyceride solid lipid nano granule of the present invention, it the advantage is that：（1）Using sweet
Oily diester as solid lipid nano granule lipid carrier, with excellent physiological function effect.（2）Different aliphatic acid formation
Diglyceride can have more lattice defects when forming solid lipid nano granule, and then have more preferable embedding to medicine
Efficiency and entrapment stability.
Embodiment
The specific preparation method of the present invention, but protection scope of the present invention are illustrated by following embodiment, not office
It is limited to this.
Embodiment 1
Weigh 0.1 gram of 1- laurate -3- palmitic acid diester, heating water bath obtains liquid oil phase to 70 DEG C；0.1 is weighed in addition
Gram soybean lecithin, 0.3 gram of Tween 80,2.0 grams of distilled water, three are mixed to form emulsifier solution i.e. aqueous phase, and heating water bath is extremely
70 DEG C, aqueous phase can be taken out to the dissolving that vortex promotes soybean lecithin for several times during heating.At this temperature, by water-oil phase
It is quick to mix, until form thick emulsion, absolute ethyl alcohol is then added dropwise into thick emulsion to forming bright micro- of clarification
Emulsion, and quickly take 1 milliliter of the microemulsion of heat to be scattered in magnetic agitation in 25 milliliters of 2~10 DEG C of cold water and obtain 1- bays
Acid -3- palmitic acid diester solid lipid nano granule dispersion liquids.
Freshly prepared nano dispersion fluid particle diameter is 295.1 ± 4.670 nm, and PDI is 0.198 ± 0.022, Zeta-
Potential is
- 22.5 ± 1.13 mV, particle diameter is 243.1 ± 0.4359 nm after storing one month, and PDI is 0.204 ± 0.008, Zeta-
Potential is -20.1 ± 0.416 mV.
Embodiment 2
Weigh 0.24 gram of 1- laurate -3- palmitic acid diester, heating water bath obtains liquid oil phase to 70 DEG C；Weigh in addition
0.038 gram of soybean lecithin, 0.922 gram of Tween 80,1.2 grams of distilled water, three are mixed to form emulsifier solution i.e. aqueous phase, water-bath
70 DEG C are heated to, aqueous phase can be taken out to the dissolving that vortex promotes soybean lecithin for several times during heating.At this temperature, by oil
Water two-phase is quickly mixed, until forming thick emulsion, absolute ethyl alcohol is then added dropwise into thick emulsion saturating to clarification is formed
Bright microemulsion, and quickly take 1 milliliter of the microemulsion of heat to be scattered in magnetic agitation in 25 milliliters of 2~10 DEG C of cold water and obtain 1-
Laurate -3- palmitic acid diester solid lipid nano granule dispersion liquids.
Brand-new obtains nano dispersion fluid particle diameter for 115.6 ± 1.308 nm, and PDI is 0.403 ± 0.009, Zeta-
potential
For -11.5 ± 0.231 mV.
Embodiment 3
Weigh 0.2 gram of 1- laurate -3- palmitic acid diester, heating water bath obtains liquid oil phase to 70 DEG C；0.2 is weighed in addition
Gram soybean lecithin, 0.6 gram of Tween 80,3.0 grams of distilled water, three are mixed to form emulsifier solution i.e. aqueous phase, and heating water bath is extremely
70 DEG C, aqueous phase can be taken out to the dissolving that vortex promotes soybean lecithin for several times during heating.At this temperature, by water-oil phase
It is quick to mix, until form thick emulsion, absolute ethyl alcohol is then added dropwise into thick emulsion to forming bright micro- of clarification
Emulsion, and quickly take heat 1 milliliter of microemulsion be scattered in magnetic agitation in 5 milliliters of 2~10 DEG C of cold water obtain 1- laurate-
3- palmitic acid diester solid lipid nano granule dispersion liquids.
Brand-new obtains nano dispersion fluid particle diameter for 249.3 ± 4.738 nm, and PDI is 0.117 ± 0.05, Zeta-
Potential is
-11.6±0.596 mV。
Claims (10)
1. a kind of preparation method based on diglyceride solid lipid nano granule, it is characterised in that it is prepared by following methods
Obtain：
a）Weighing qs glycerin diester and being heated to design temperature T makes it be completely melt to form oil phase or the breast by appropriate poorly water-soluble
Agent is thermally formed liquid oil phase with diglyceride；
b）Weigh appropriate emulsifying agent and distilled water is mixed to form aqueous phase, and be heated to temperature T；
c）Aqueous phase and oil phase are stirred into mixing under identical temperature T and form thick emulsion within 5~10 minutes；
d）Appropriate absolute ethyl alcohol is added dropwise into thick emulsion until forming the bright microemulsion of clarification；
e）The microemulsion of heat is scattered in formation solid lipid nano granule dispersion liquid in 2~10 DEG C of cold water by a certain percentage.
2. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that described
Step a in the heating-up temperature T of diglyceride be more than selected diglyceride fusing point 5~10 DEG C of temperature.
3. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that described
Step b in emulsifying agent be ionic emulsifying agent and nonionic emulsifier compounding, such as soybean lecithin, SDS plasma types
The compounding of the nonionic emulsifier such as emulsifying agent and polysorbas20, polysorbate60, Tween 80；But it is preferred that the small lecithin of bio-toxicity with
Tween.
4. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that described
Step b in aqueous phase both can be comprising the good emulsifying agent of all emulsifying agents or part aqueous, according to compounding
Emulsifying agent dissolubility in water judges.
5. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that step
The mass ratio of diglyceride and emulsifying agent is 1 in a, b：3~1：8, and the compound proportion of two class emulsifying agents can be in emulsifying agent
Ionic with it is non-ionic be 1：3~1：49, the mass concentration of diglyceride is 1%~10% in whole system.
6. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that described
In step c by oil phase it is mixed with water when quickly should mix while hot, to avoid liquid oil phase by cold crystallization.
7. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that described
The basis for estimation that thick emulsion is formed in step c is that, by sample slight wobble, observation wall built-up backflow emulsion color and luster is homogeneous, more bright
It is defined.
8. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that described
The addition of absolute ethyl alcohol, which should be, in step d is added dropwise, and is preferably that band needle applicator is added dropwise, it is ensured that with fine drop
Form is added.
9. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that described
The microemulsion of heat, which is dispersed in cold water, in step e can make the rapid crystallisation by cooling of liquid oil phase and form solid lipid nano granule point
Dispersion liquid, hot microemulsion is 1 with cold scattered water volume ratio:5~1：25.
10. the preparation method according to claim 1 based on diglyceride solid lipid nano granule, it is characterised in that institute
State the solid lipid nano granule dispersion liquid obtained in step e and can further be freeze-dried and obtain freeze-dried powder, as solid lipid is received
The grain of rice.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710705668.XA CN107320461A (en) | 2017-08-17 | 2017-08-17 | A kind of preparation method based on diglyceride solid lipid nano granule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710705668.XA CN107320461A (en) | 2017-08-17 | 2017-08-17 | A kind of preparation method based on diglyceride solid lipid nano granule |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107320461A true CN107320461A (en) | 2017-11-07 |
Family
ID=60223946
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710705668.XA Pending CN107320461A (en) | 2017-08-17 | 2017-08-17 | A kind of preparation method based on diglyceride solid lipid nano granule |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107320461A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108969477A (en) * | 2018-08-14 | 2018-12-11 | 武汉轻工大学 | Diglyceride base nano structured lipid carrier dispersion liquid and its preparation method and application |
| CN109122684A (en) * | 2018-08-14 | 2019-01-04 | 武汉轻工大学 | Carvacrol solid lipid nano granule dispersion liquid with bacteriostatic activity and its preparation method and application |
| CN109430428A (en) * | 2018-10-23 | 2019-03-08 | 东北农业大学 | A kind of preparation method of structured lipid OPO nanoemulsions |
| CN112868816A (en) * | 2021-01-26 | 2021-06-01 | 暨南大学 | Preparation method of water-in-oil emulsion gel based on diglyceride solid lipid nanoparticles |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060083781A1 (en) * | 2004-10-14 | 2006-04-20 | Shastri V P | Functionalized solid lipid nanoparticles and methods of making and using same |
| CN107019682A (en) * | 2017-04-13 | 2017-08-08 | 中国药科大学 | A kind of Nimodipine lipid nanoparticle and its preparation technology |
-
2017
- 2017-08-17 CN CN201710705668.XA patent/CN107320461A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060083781A1 (en) * | 2004-10-14 | 2006-04-20 | Shastri V P | Functionalized solid lipid nanoparticles and methods of making and using same |
| CN107019682A (en) * | 2017-04-13 | 2017-08-08 | 中国药科大学 | A kind of Nimodipine lipid nanoparticle and its preparation technology |
Non-Patent Citations (1)
| Title |
|---|
| 李向荣: "《药剂学》", 28 February 2010, 中国医药科技出版社 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108969477A (en) * | 2018-08-14 | 2018-12-11 | 武汉轻工大学 | Diglyceride base nano structured lipid carrier dispersion liquid and its preparation method and application |
| CN109122684A (en) * | 2018-08-14 | 2019-01-04 | 武汉轻工大学 | Carvacrol solid lipid nano granule dispersion liquid with bacteriostatic activity and its preparation method and application |
| CN109122684B (en) * | 2018-08-14 | 2021-03-26 | 武汉轻工大学 | Carvacrol solid lipid nanoparticle dispersion liquid with antibacterial activity and preparation method and application thereof |
| CN109430428A (en) * | 2018-10-23 | 2019-03-08 | 东北农业大学 | A kind of preparation method of structured lipid OPO nanoemulsions |
| CN112868816A (en) * | 2021-01-26 | 2021-06-01 | 暨南大学 | Preparation method of water-in-oil emulsion gel based on diglyceride solid lipid nanoparticles |
| CN112868816B (en) * | 2021-01-26 | 2022-11-08 | 暨南大学 | Preparation method of water-in-oil emulsion gel based on diglyceride solid lipid nanoparticles |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107320461A (en) | A kind of preparation method based on diglyceride solid lipid nano granule | |
| CN106580919B (en) | A kind of ganoderma lucidum spore oil microcapsule powder and its preparation method and application | |
| JPS60199833A (en) | Preparation of w/o/w-type composite emulsion for pharmaceutical, cosmetic, etc. | |
| Efendy Goon et al. | Palm oil in lipid-based formulations and drug delivery systems | |
| Tamilvanan | Formulation of multifunctional oil-in-water nanosized emulsions for active and passive targeting of drugs to otherwise inaccessible internal organs of the human body | |
| Feng et al. | Preparation and characterization of zein-based phytosterol nanodispersions fabricated by ultrasonic assistant anti-solvent precipitation | |
| WO2008020680A1 (en) | The method of preparing a microcapsule containing unsaturated fatty acids, the microcapsule prepared by the method, and articles containing the microcapsule | |
| CN112869165A (en) | Preparation method of phytosterol nano liposome | |
| Li et al. | Preparation and characterization of nanoscale complex liposomes containing medium-chain fatty acids and vitamin C | |
| CN105748416B (en) | A kind of DHA nano-emulsion freeze-dried powder and preparation method thereof | |
| Eh Suk et al. | Development of nanostructured lipid carrier (NLC) assisted with polysorbate nonionic surfactants as a carrier for l-ascorbic acid and Gold Tri. E 30 | |
| CN102552328A (en) | Preparation method of compound fish oil nano-emulsion | |
| Panpipat et al. | Thermal properties and nanodispersion behavior of synthesized β-sitosteryl acyl esters: A structure–activity relationship study | |
| CN111632154A (en) | Phase-transition nanobubble, preparation method and application thereof | |
| CN101627970A (en) | Method for preparing medicinal solid lipid nano particle | |
| Hijo et al. | High-intensity ultrasound assisted-emulsification using ionic liquids as novel naturally-derived emulsifiers for food industry applications | |
| CN104490779A (en) | Flurbiprofen axetil fat emulsion injection | |
| CN102764456B (en) | Vascular occlusive agent, application thereof and preparation method | |
| CN113558237A (en) | Preparation method of capsaicin-loaded two-phase network water-in-oil high internal phase emulsion | |
| CN109864244A (en) | A kind of method that aurantiin improves beta carotene liposome stability | |
| JP7182630B2 (en) | double emulsion | |
| JPH03181415A (en) | Method for modifying liposome surface and device for modifying | |
| CN109198634A (en) | A kind of phytosterin ester nanocapsule lotion and its preparation method and application | |
| KR102577778B1 (en) | pH-responsive capsosome using chitosan-coated solid lipid nanoparticles as core | |
| Lokhande | Recent Trends in Multiple Emulsion-A Comprehensive Review |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20171107 |