CN109568292A - A kind of microgel and preparation method thereof containing GPC - Google Patents
A kind of microgel and preparation method thereof containing GPC Download PDFInfo
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- CN109568292A CN109568292A CN201811638951.6A CN201811638951A CN109568292A CN 109568292 A CN109568292 A CN 109568292A CN 201811638951 A CN201811638951 A CN 201811638951A CN 109568292 A CN109568292 A CN 109568292A
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- 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
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
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- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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Abstract
The invention discloses a kind of microgel and preparation method thereof containing GPC, the microgel containing GPC, it is characterised in that including following components: sodium alginate, water, glycerolphosphocholine, oily phase, emulsifier, coagulator；The purpose of the invention is to overcome be difficult to operate in GPC preparation in the prior art, easily decompose, be difficult to control release the deficiencies of place, one kind is provided using L- α-glycerolphosphocholine fortified aqueous as core material, using sodium alginate gel as microgel containing GPC of wall material and preparation method thereof.The sodium alginate microgel average grain diameter is 10-50 microns, and sodium alginate gel shell average thickness is 1-5 microns, and gel particle shape rounding, particle diameter distribution is relatively narrow, and can be with storage-stable, slow release glycerolphosphocholine.
Description
Technical field
The invention belongs to microcapsules application, biomedicine technical field, in particular to a kind of gel beads and its system containing GPC
Preparation Method.
Background technique
L-a-- glycerolphosphocholine (L-a-glyceryl phosphorylcholine, GPC) it is also known as sweet phosphoric acid gallbladder
Alkali, sweet Phosphorylcholine, glycerolphosphocholine.
Glycerolphosphocholine as drug or health care product for treating cerebral infarction, Alzheimer disease, and
Multi infarct dementia has listed for many years in European & American Market and Japan, South Korea.
GPC sterling is a kind of white powder, there is the slightly sweet taste close with mannitol, water-soluble fine, can be to appoint with water
Meaning ratio is miscible.
Most GPC crystal forms all have apparent hygroscopicity, than more intractable in formulation process.
It is prepared into tablet or hard capsule, needs to be added more auxiliary material to solve the problems, such as that its moisture absorption deliquesces.
Dilute GPC aqueous solution is easier to be absorbed to be easy to corrupt mildew by mushroom and algae.GPC is in gastrointestinal tract interior suction
It receives rapidly, is difficult to after oral and stablizes release, be administered continuously.
Summary of the invention
The purpose of the invention is to overcome be difficult to operate in GPC preparation in the prior art, easily decompose, be difficult to control release
The deficiencies of place, provide one kind using L- α-glycerolphosphocholine fortified aqueous as core material, using sodium alginate gel as wall material
Microgel containing GPC and preparation method thereof.The sodium alginate microgel average grain diameter is 10-50 microns, sodium alginate gel shell
Average thickness is 1-5 microns, and gel particle shape rounding, particle diameter distribution is relatively narrow, and can be with storage-stable, slow release glycerol
Phosphatidyl choline.
In order to achieve the above object, the present invention uses following scheme:
A kind of microgel containing GPC, it is characterised in that including following components: sodium alginate, water, glycerolphosphocholine,
Oily phase, emulsifier, coagulator；Wherein the sodium alginate, glycerolphosphocholine and water mixed solution are as water phase；
The sodium alginate and the mass ratio of water phase are 0.01-0.1:1；
The oil is mutually 1-10:1 with the volume ratio of water phase；
The volume ratio of the emulsifier and oily phase is 0.0005-0.02:1；
The coagulator and the mass ratio of water phase are 0.005-0.1:1；
The mass ratio of the sodium alginate, glycerolphosphocholine and water is 1-10:100:8-22.
Preferential, the oil is mutually edible oil.
Preferential, the edible oil is one of soybean oil, olive oil, peanut oil.
Preferential, the emulsifier is water-in-oil emulsifier.
Preferential, the water-in-oil emulsifier is one of sorbester p17, sorbester p18 or polysorbas20.
Preferential, the coagulator is calcium salt coagulator.
Preferential, the calcium salt coagulator is the mixed of one or more of calcium chloride, calcium lactate, calcium gluconate
Close object.
A kind of preparation method of the microgel containing GPC of the present invention, it is characterised in that the following steps are included:
A, sodium alginate is dissolved in the water, glycerolphosphocholine is then added, stirred evenly, form the sea containing GPC
Alginic acid sodium water solution；
B, oily phase is sequentially added in the sodium alginate aqueous solution into step A and emulsifier, stirring and emulsifying obtain Water-In-Oil
Type lotion；
C, coagulator is added in the water-in-oil emulsion into step B, and continues to stir, form microgel；
D, it is separated by filtration using nuclepore membrane filter, sodium alginate microgel is made in filter cake.
Preferential, further include step E: the oily phase that washing removes remaining is carried out to the filter cake in step D using ethyl alcohol.
Preferential, emulsifying temperature is room temperature to 100 DEG C in step B.
In conclusion the present invention compared with the existing technology the beneficial effect is that:
Sodium alginate microgel prepared by the present invention containing GPC, particle diameter distribution is relatively narrow, and gel particles sphericity is preferable, partial size
The regulation that can be convenient with wall thickness, gel wall material and the GPC compatible degree as effective component are preferable.It is made after microgel,
The storage stability of GPC is improved obviously, and rate of release is uniform and stable in aqueous solution.
Specific embodiment
The invention will be further described With reference to embodiment:
Embodiment 1
Sodium alginate 5g is dissolved in 100g water, is warming up to 45 degrees Celsius, and L- α-glycerophosphatide acyl is added in stirring and dissolving
Choline 15g, stirs evenly, as water phase.
Soybean salad oil 500ml is sequentially added into above-mentioned aqueous phase solution, sorbester p17 emulsifier 5ml makes at 45 degrees Celsius
With mechanical agitator high degree of agitation 30 minutes, white water-in-oil emulsion is made.
Calcium chloride 2g is added into above-mentioned emulsion as coagulator, and high degree of agitation 1 hour.
Resulting lotion is filtered using nuclepore membrane filter, filter cake is sodium alginate microgel obtained, be can be used
100ml ethanol washing is to remove remaining soybean salad oil.Filtrate is soybean salad oil to be recycled.
Embodiment 2
Sodium alginate 3g is dissolved in 100g water, is warming up to 50 degrees Celsius, and L- α-glycerophosphatide acyl is added in stirring and dissolving
Choline 15g, stirs evenly, as water phase.
Soybean salad oil 500ml is sequentially added into above-mentioned aqueous phase solution, sorbester p17 emulsifier 5ml makes at 50 degrees Celsius
With mechanical agitator high degree of agitation 30 minutes, white water-in-oil emulsion is made.
Calcium lactate 2g is added into above-mentioned emulsion as coagulator, and high degree of agitation 1 hour.Use nuclepore membrane filter
Filtering, filter cake is sodium alginate microgel obtained, and 100ml ethanol washing can be used to remove the soybean salad oil of remaining.
Embodiment 3
Sodium alginate 5g is dissolved in 100g water, is warming up to 48 degrees Celsius, and L- α-glycerophosphatide acyl is added in stirring and dissolving
Choline 15g, stirs evenly, as water phase.
Soybean salad oil 500ml is sequentially added into above-mentioned aqueous phase solution, sorbester p17 emulsifier 5ml makes at 46 degrees Celsius
With mechanical agitator high degree of agitation 30 minutes, white water-in-oil emulsion is made.
The aqueous solution that addition calcium chloride 2g and water 5ml are made into above-mentioned emulsion is as coagulator, and high degree of agitation 1 is small
When.
Ethyl alcohol 100ml is added in resulting lotion, and stirs at low speed stirring demulsification, after demulsification, upper layer is soybean salad
Oil, lower layer are water layers, and the microgel obtained containing GPC is deposited on water layer lower part.Divide and remove upper layer oil reservoir, lower layer uses miillpore filter
Filter filtering, what is obtained is sodium alginate microgel, and 100ml ethanol washing can be used to remove the oily phase of remaining.
Embodiment 4
A kind of microgel containing GPC, it is characterised in that including following components: sodium alginate, water, glycerolphosphocholine,
Oily phase, emulsifier, coagulator；Wherein the sodium alginate, glycerolphosphocholine and water mixed solution are as water phase；
The sodium alginate and the mass ratio of water phase are 0.01:1；
The oil is mutually 1:1 with the volume ratio of water phase；
The volume ratio of the emulsifier and oily phase is 0.0005:1；
The coagulator and the mass ratio of water phase are 0.005:1；
The mass ratio of the sodium alginate, glycerolphosphocholine and water is 1:100:8.
The oil is mutually soybean oil.
The emulsifier is sorbester p17.
The coagulator is calcium chloride.
Preparation method, comprising the following steps:
A, sodium alginate is dissolved in the water, glycerolphosphocholine is then added, stirred evenly, form the sea containing GPC
Alginic acid sodium water solution；
B, oily phase is sequentially added in the sodium alginate aqueous solution into step A and emulsifier, stirring and emulsifying obtain Water-In-Oil
Type lotion；Emulsifying temperature is room temperature.
C, coagulator is added in the water-in-oil emulsion into step B, and continues to stir, form microgel；
D, it is separated by filtration using nuclepore membrane filter, sodium alginate microgel is made in filter cake.
E: the oily phase that washing removes remaining is carried out to the filter cake in step D using ethyl alcohol.
Embodiment 5
A kind of microgel containing GPC, it is characterised in that including following components: sodium alginate, water, glycerolphosphocholine,
Oily phase, emulsifier, coagulator；Wherein the sodium alginate, glycerolphosphocholine and water mixed solution are as water phase；
The sodium alginate and the mass ratio of water phase are 0.1:1；
The oil is mutually 10:1 with the volume ratio of water phase；
The volume ratio of the emulsifier and oily phase is 0.02:1；
The coagulator and the mass ratio of water phase are 0.1:1；
The mass ratio of the sodium alginate, glycerolphosphocholine and water is 10:100:22.
The oil is mutually olive oil.
The emulsifier is sorbester p18.
The coagulator is calcium lactate.
Preparation method, comprising the following steps:
A, sodium alginate is dissolved in the water, glycerolphosphocholine is then added, stirred evenly, form the sea containing GPC
Alginic acid sodium water solution；
B, oily phase is sequentially added in the sodium alginate aqueous solution into step A and emulsifier, stirring and emulsifying obtain Water-In-Oil
Type lotion；Emulsifying temperature is 100 DEG C；
C, coagulator is added in the water-in-oil emulsion into step B, and continues to stir, form microgel；
D, it is separated by filtration using nuclepore membrane filter, sodium alginate microgel is made in filter cake.
E: the oily phase that washing removes remaining is carried out to the filter cake in step D using ethyl alcohol.
Embodiment 6
A kind of microgel containing GPC, it is characterised in that including following components: sodium alginate, water, glycerolphosphocholine,
Oily phase, emulsifier, coagulator；Wherein the sodium alginate, glycerolphosphocholine and water mixed solution are as water phase；
The sodium alginate and the mass ratio of water phase are 0.05:1；
The oil is mutually 5:1 with the volume ratio of water phase；
The volume ratio of the emulsifier and oily phase is 0.001:1；
The coagulator and the mass ratio of water phase are 0.05:1；
The mass ratio of the sodium alginate, glycerolphosphocholine and water is 5:100:15.
The oil is mutually peanut oil.
The emulsifier is polysorbas20.
The coagulator is calcium gluconate.
Preparation method, comprising the following steps:
A, sodium alginate is dissolved in the water, glycerolphosphocholine is then added, stirred evenly, form the sea containing GPC
Alginic acid sodium water solution；
B, oily phase is sequentially added in the sodium alginate aqueous solution into step A and emulsifier, stirring and emulsifying obtain Water-In-Oil
Type lotion；Emulsifying temperature is 50 DEG C
C, coagulator is added in the water-in-oil emulsion into step B, and continues to stir, form microgel；
D, it is separated by filtration using nuclepore membrane filter, sodium alginate microgel is made in filter cake.
E: the oily phase that washing removes remaining is carried out to the filter cake in step D using ethyl alcohol.
Embodiment 7
A kind of microgel containing GPC, it is characterised in that including following components: sodium alginate, water, glycerolphosphocholine,
Oily phase, emulsifier, coagulator；Wherein the sodium alginate, glycerolphosphocholine and water mixed solution are as water phase；
The sodium alginate and the mass ratio of water phase are 0.03:1；
The oil is mutually 2:1 with the volume ratio of water phase；
The volume ratio of the emulsifier and oily phase is 0.001:1；
The coagulator and the mass ratio of water phase are 0.008:1；
The mass ratio of the sodium alginate, glycerolphosphocholine and water is 1:100:22.
The oil is mutually soybean oil.
The emulsifier is sorbester p17.
The coagulator is the mixture of calcium lactate, calcium gluconate.
Preparation method, comprising the following steps:
A, sodium alginate is dissolved in the water, glycerolphosphocholine is then added, stirred evenly, form the sea containing GPC
Alginic acid sodium water solution；
B, oily phase is sequentially added in the sodium alginate aqueous solution into step A and emulsifier, stirring and emulsifying obtain Water-In-Oil
Type lotion；Emulsifying temperature is 40 DEG C
C, coagulator is added in the water-in-oil emulsion into step B, and continues to stir, form microgel；
D, it is separated by filtration using nuclepore membrane filter, sodium alginate microgel is made in filter cake.
E: the oily phase that washing removes remaining is carried out to the filter cake in step D using ethyl alcohol.
Basic principles and main features and advantages of the present invention of the invention have been shown and described above.The skill of the industry
Art personnel it should be appreciated that the present invention is not limited to the above embodiments, the above embodiments and description only describe
The principle of the present invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these
Changes and improvements all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and
Its equivalent thereof.
Claims (10)
1. a kind of microgel containing GPC, it is characterised in that including following components: sodium alginate, water, glycerolphosphocholine, oil
Phase, emulsifier, coagulator；Wherein the sodium alginate, glycerolphosphocholine and water mixed solution are as water phase；
The sodium alginate and the mass ratio of water phase are 0.01-0.1:1；
The oil is mutually 1-10:1 with the volume ratio of water phase；
The volume ratio of the emulsifier and oily phase is 0.0005-0.02:1；
The coagulator and the mass ratio of water phase are 0.005-0.1:1；
The mass ratio of the sodium alginate, glycerolphosphocholine and water is 1-10:100:8-22.
2. a kind of microgel containing GPC according to claim 1, it is characterised in that the oil is mutually edible oil.
3. a kind of microgel containing GPC according to claim 2, it is characterised in that the edible oil is soybean oil, olive
One of oil, peanut oil.
4. a kind of microgel containing GPC according to claim 1, it is characterised in that the emulsifier is water-in-oil emulsion
Agent.
5. a kind of microgel containing GPC according to claim 4, it is characterised in that the water-in-oil emulsifier is sapn
80, one of sorbester p18 or polysorbas20.
6. a kind of microgel containing GPC according to claim 1, it is characterised in that the coagulator is calcium salt coagulator.
7. a kind of microgel containing GPC according to claim 6, it is characterised in that the calcium salt coagulator be calcium chloride,
The mixture of one or more of calcium lactate, calcium gluconate.
8. a kind of preparation method of the microgel containing GPC, it is characterised in that the following steps are included:
A, sodium alginate is dissolved in the water, glycerolphosphocholine is then added, stirred evenly, form the alginic acid containing GPC
Sodium water solution；
B, oily phase and emulsifier, stirring and emulsifying are sequentially added in the sodium alginate aqueous solution into step A, obtain water-in-oil type cream
Liquid；
C, coagulator is added in the water-in-oil emulsion into step B, and continues to stir, form microgel；
D, it is separated by filtration using nuclepore membrane filter, sodium alginate microgel is made in filter cake.
9. a kind of preparation method of microgel containing GPC according to claim 8, it is characterised in that further include step E: adopting
The oily phase that washing removes remaining is carried out to the filter cake in step D with ethyl alcohol.
10. a kind of preparation method of microgel containing GPC according to claim 8, it is characterised in that emulsify temperature in step B
Degree is room temperature to 100 DEG C.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113403045A (en) * | 2021-06-29 | 2021-09-17 | 中国石油大学(华东) | Water-in-oil type self-adaptive polymer emulsion profile control system and preparation method and application thereof |
| CN116035946A (en) * | 2022-10-25 | 2023-05-02 | 上海美自无双生物科技有限公司 | Method for preparing ceramide cell phospholipid composition by complex coacervation method and application thereof |
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2018
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113403045A (en) * | 2021-06-29 | 2021-09-17 | 中国石油大学(华东) | Water-in-oil type self-adaptive polymer emulsion profile control system and preparation method and application thereof |
| CN116035946A (en) * | 2022-10-25 | 2023-05-02 | 上海美自无双生物科技有限公司 | Method for preparing ceramide cell phospholipid composition by complex coacervation method and application thereof |
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Application publication date: 20190405 |