CN101474156B - Vitamin C precursor liposome and preparation method thereof - Google Patents

Vitamin C precursor liposome and preparation method thereof Download PDF

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Publication number
CN101474156B
CN101474156B CN2009100455133A CN200910045513A CN101474156B CN 101474156 B CN101474156 B CN 101474156B CN 2009100455133 A CN2009100455133 A CN 2009100455133A CN 200910045513 A CN200910045513 A CN 200910045513A CN 101474156 B CN101474156 B CN 101474156B
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vitamin
liposome
water
precursor
preparation
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CN101474156A (en
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李成亮
柳郁
高保安
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Shengwei Pharmaceutical (Shanghai) Co., Ltd.
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Shanghai Laipusen Bio-Chemical Co Ltd
Shanghai Laibo Bio-chemical Co Ltd
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Abstract

The invention relates to the technical fields of medicament and cosmetics, in particular to a vitamin C proliposome and a preparation method thereof. The vitamin C proliposome can be used for preparing a transdermal preparation and cosmetics. The vitamin C proliposome is a solid granular preparation which ensures that the stabilities of the vitamin C and the proliposome are improved, and the vitamin C proliposome can revert to a vitamin C lipidosome only by adding a small amount of water or aqueous solution for hydration before the vitamin C proliposome is in use, and thereby, a sufficient amount of vitamin C lipidosome is added into the transdermal preparation and the cosmetics according to need so that the content of the vitamin C in the transdermal preparation and the cosmetics reaches the required dosage, and thereby, the efficacy is improved.

Description

A kind of vitamin C precursor liposome and application thereof
Technical field
The present invention relates to medicine and cosmetics technical field, is a kind of vitamin C precursor liposome and preparation method thereof, and vitamin C precursor liposome can be used for preparing percutaneous drug delivery preparation or cosmetics.
Background technology
Vitamin C is one of nutrient of needed by human, and it participates in multiple reaction in vivo.Vitamin C can promote the synthetic of ossein, is beneficial to the healing sooner of tissue injury mouth; Be a kind of main antioxidant, prevent the infringement of radical pair human body, be used to prevent skin carcinoma.In addition, vitamin C can increase the activity of Skin Cell effectively, increases the elasticity and the pliability of skin, prevents the aging of skin; Suppress Tyrosinase and vat black pigment, and desalinate established speckle, suppress melanin and form the Pear Power freckle effect.Therefore, vitamin C all has application in the control of various dermatosis and cosmetics.But owing to contain more unsaturated double-bond, less stable in the vitamin C structure; The vitamin C molecular weight is bigger, and water solublity is stronger, is difficult for seeing through skin.These effects limit the application of vitamin C in percutaneous drug delivery preparation or cosmetics.
Liposome is the hydrophilic vesicle that is made up of phospholipid bilayer; Since liposome have raising by the stability of entrapped drug, promote that drug transdermal absorbs, the action time of prolong drug, to the targeting of local diseased region, reduce characteristics such as poisonous side effect of medicine; Therefore, liposome has been widely used in the technical recipe of percutaneous drug delivery preparation and cosmetics as pharmaceutical carrier.But vitamin C liposome is a kind of liposome turbid liquor, aspect stable, also has tangible deficiency.This be because:
1. liposome is a kind of thermodynamic instability systems as colloidal particles, in aqueous solution, is prone to assemble, fusion, sedimentation, the oxidation Decomposition of phospholipid and the seepage of entrapped drug etc., thereby causes the instability of liposome;
2. the unstability of vitamin C structure makes it in aqueous solution, seem more unstable;
3. vitamin C liposome content under the suspension state often is restricted; As far as some Percutaneously administrable prepn or cosmetics; The Vitamin C content that needs is higher, but can not mix too much vitamin C liposome suspension again in the prescription, otherwise too rare; This just is difficult to improve ascorbic dosage, and the deficiency of dosage can directly influence the effect of percutaneous drug delivery preparation or cosmetics.
Summary of the invention
The present invention provides a kind of vitamin C precursor liposome; It is a kind of granular solids preparation, can not only improve the stability of vitamin C and liposome, and adds low amounts of water or aqueous solution hydration facing with preceding need; Just can revert back to vitamin C liposome; Thereby can in percutaneous drug delivery preparation or cosmetics, add the vitamin C precursor liposome of q.s as required, make the Vitamin C content in percutaneous drug delivery preparation or the cosmetics reach required dosage, improve curative effect.
The component and the proportioning of vitamin C precursor liposome of the present invention are following:
Component percentages (W/V)
Vitamin C 0.1%-80%
Liposome framework material 1%-20%
Stabilizing agent 0-20%
Proppant 0.1%-50%
Said liposome framework material is selected from the 1-3 kind in soybean lecithin, Ovum Gallus domesticus Flavus lecithin, DSPC, dipalmitoyl phosphatidyl choline, dimyristoyl phosphatidyl choline, ceramide, the brejs nonionic surfactant;
Said stabilizing agent is selected from the 1-3 kind in cholesterol, stigmasterol, sitosterol, poloxamer, sodium lauryl sulphate, Polysorbate, sodium cholate, the sodium deoxycholate;
Said proppant is selected from the 1-2 kind in mannitol, glucose, sorbitol, sucrose, lactose, trehalose, sodium chloride, the polyvinylpyrrolidone.
The method for preparing of vitamin C precursor liposome of the present invention is following:
1. preparation lipid soln:
With liposome framework material and stabilizing agent heating and melting or use organic solvent dissolution, process lipid soln by proportioning; Said organic solvent is selected from the 1-2 kind in chloroform, ethanol, dichloromethane, the ether;
2. preparation pro-liposome, method has following two kinds:
1) vitamin C is fully mixed with proppant earlier by proportioning, again with above-mentioned lipid soln through fluid bed in the spray-drying process of routine with mixed vitamin C and mixed with proppants, must vitamin C precursor liposome;
2) earlier by routine with above-mentioned lipid soln through film dispersion method or fusion method be dissolved with vitamin C with the aqueous solution of proppant is processed vitamin C liposome, again vitamin C liposome is passed through lyophilization or spray drying, must vitamin C precursor liposome.
The present invention is prepared into pro-liposome with vitamin C earlier, when mixing percutaneous drug delivery preparation or cosmetics, makes its hydration revert back to vitamin C liposome again, has the following advantages:
1. vitamin C precursor liposome is a solid preparation, good stability, long shelf-life, with preceding need add water or aqueous solution hydration vibration conventional liposome.Thereby instability problem such as the gathering of vitamin C liposome in suspension, sedimentation, fusion, seepage have been solved.
2. further improve ascorbic stability.Because vitamin C precursor liposome is a kind of solid preparation, labile drugs is more stable than liquid condition under solid state.
3. when preparing percutaneous drug delivery preparation and cosmetics; When mixing vitamin C precursor liposome, only need add low amounts of water or aqueous solution just can make its hydration revert back to vitamin C liposome; Thereby the vitamin C precursor liposome that can in percutaneous drug delivery preparation and cosmetics, add q.s as required; But be the content distributed in demand of the vitamin C liposome in percutaneous drug delivery preparation or the cosmetics, thereby satisfy the demand of different preparations, and make operation more convenient.
The specific embodiment
Combine embodiment that the present invention is described in detail at present.
Embodiment 1:
Get vitamin C 10g, soybean lecithin 30g, cholesterol 30g, poloxamer 40g, glucose 200g, chloroform 200mL.
Liposome framework material soybean lecithin, poloxamer, cholesterol are added in the round-bottomed flask of 1000mL; With chloroform the liposome framework material is dissolved; Put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make in the round-bottomed flask bottom to become one deck lipid membrane, subsequent use; Glucose and vitamin C are dissolved in the water of 800mL, filter, filtrating is poured in the above-mentioned round-bottomed flask; Hydration, vibration, adding water to the mixing material cumulative volume is 1000mL; Through homogenization processing (8000psi, 3 times), obtain liposome turbid liquor; Through lyophilization (temperature-50 ℃, vacuum 100mtorr), promptly get vitamin C precursor liposome.
Embodiment 2:
Vitamin C 100g, Ovum Gallus domesticus Flavus lecithin 50g, cholesterol 50g, sucrose 40g.
Ovum Gallus domesticus Flavus lecithin, cholesterol are put in the conical flask, and heating and melting places 80 ℃ of waters bath with thermostatic control subsequent use; , filter sucrose and vitamin C dissolving with 800mL water, the water-bath of will filtrating is heated to and the lipid soln uniform temp; Aqueous solution is mixed with the lipid soln vibration, cooling, adding water to the mixing material cumulative volume is 1000mL; Through homogenization processing (12000psi, 2 times), obtain liposome turbid liquor; Spray-dried by routine, promptly get vitamin C precursor liposome.
Embodiment 3:
Vitamin C 50g gathers dioxy ethylene cetyl ether 60g, stigmasterol 40g, poloxamer 50g, trehalose 80g, ether 200mL.
To gather dioxy ethylene cetyl ether, cholesterol is added in the 500mL conical flask, it is subsequent use with their dissolvings to add ether; Water with 800mL dissolves trehalose, poloxamer and vitamin C, filters, and filtrating is poured in the conical flask; Put in 45 ℃ of waters bath with thermostatic control magnetic agitation, mixing speed 500rpm; The volatilization organic solvent obtains liposome turbid liquor, through lyophilization (temperature-50 ℃; Vacuum 80mtorr), promptly get vitamin C precursor liposome.
Embodiment 4:
Vitamin C 150g, soybean lecithin 75g, lactose 50g, glucose 50g, cholesterol 15g, chloroform 200ml.
Soybean lecithin, cholesterol are added in the round-bottomed flask of 1000mL, add chloroform they are dissolved, put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make in the round-bottomed flask bottom to become one deck lipid membrane, subsequent use.Water with 800ml dissolves vitamin C, lactose, glucose, filters, and filtrating is poured in the above-mentioned flask into hydration; Vibration, adding water to the mixing material cumulative volume is 1000mL, through homogenization processing (20000psi, 4 times); Get liposome turbid liquor, spray-dried, promptly get vitamin C precursor liposome.
Embodiment 5:
Vitamin C 120g, soybean lecithin 75g, cholesterol 15g, Polysorbate 50g, trehalose 40g, chloroform 200ml.
Soybean lecithin, cholesterol, Polysorbate are put in the 1000mL round-bottomed flask, added the 200mL chloroform and make its whole dissolvings, process lipid soln, directly be sprayed in the trehalose fluid bed that is placed with mixed vitamin C, promptly get vitamin C precursor liposome.
Embodiment 6:
Vitamin C 200g, Ovum Gallus domesticus Flavus lecithin 100g, mannitol 100g, lactose 100g, sodium lauryl sulphate 50g.
Ovum Gallus domesticus Flavus lecithin and sodium lauryl sulphate are scattered in the water of 300ml in 75 ℃ of water-baths, subsequent use; With mannitol, lactose and vitamin C dissolving, be heated to 75 ℃ with 500ml water; Both are mixed, vibration, cooling, moisturizing through homogenization processing (6000psi, 5 times), obtains liposome turbid liquor to 1000mL, through lyophilization (temperature-50 ℃, vacuum 60mtorr), promptly gets vitamin C precursor liposome.
Embodiment 7:
Vitamin C 100g, soybean lecithin 50g, mannitol 100g, ceramide 10g, poloxamer 50g.
Soybean lecithin, ceramide and poloxamer are put in the conical flask, and heating and melting places 80 ℃ of waters bath with thermostatic control subsequent use; , filter mannitol and vitamin C dissolving with 800mL water, the water-bath of will filtrating is heated to and the lipid soln uniform temp; The vibration of aqueous solution and lipid soln is mixed, cools off, moisturizing with mixeding liquid volume to 1000mL; Through homogenization processing (12000psi, 3 times), obtain liposome turbid liquor; Spray-dried, promptly get vitamin C precursor liposome.
Embodiment 8:
Vitamin C 50g, soybean lecithin 30g, mannitol 100g, ceramide 10g, sodium lauryl sulphate 10g, chloroform 100ml.
Soybean lecithin, ceramide are added in the round-bottomed flask of 1000mL, add chloroform it is dissolved, put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make lipid become thin film in the round-bottomed flask bottom, subsequent use; Water with 800ml dissolves vitamin C, mannitol and sodium lauryl sulphate, filters, and filtrating is poured in the above-mentioned flask; Hydration, the vibration, moisturizing with mixeding liquid volume to 1000mL; Through homogenization processing (15000psi, 2 times), obtain liposome turbid liquor; Spray drying promptly gets vitamin C precursor liposome.
Embodiment 9:
Vitamin C 100g, soybean lecithin 25g, Brij52 25g, mannitol 50g, trehalose 50g, sodium lauryl sulphate 10g.
Soybean lecithin, Brij52 are added in the conical flask, add the 50mL dissolved in chloroform, place 80 ℃ of waters bath with thermostatic control subsequent use; , filter mannitol, trehalose, sodium lauryl sulphate and vitamin C dissolving with 800mL water, the water-bath of will filtrating is heated to and the lipid soln uniform temp; The vibration of aqueous solution and lipid soln is mixed, cools off, moisturizing with mixeding liquid volume to 1000mL; Through homogenization processing (12000psi, 1 time), obtain liposome turbid liquor; Spray-dried, promptly get vitamin C precursor liposome.
Embodiment 10:
Vitamin C 200g, Ovum Gallus domesticus Flavus lecithin 50g, poloxamer 50g, sorbitol 100g, chloroform 200ml.
Ovum Gallus domesticus Flavus lecithin, poloxamer are added in the round-bottomed flask of 1000mL, add chloroform it is dissolved, put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make lipid become thin film in the round-bottomed flask bottom, subsequent use; Water with 800ml dissolves recipe quantity vitamin C, sorbitol, filters, and filtrating is poured in the above-mentioned flask into hydration; The vibration, moisturizing with mixeding liquid volume to 1000mL, through homogenization processing (15000psi, 4 times); Obtain liposome turbid liquor, spray drying promptly gets vitamin C precursor liposome.
Embodiment 11:
Vitamin C 50g,, ceramide 3 0g, sucrose 10g, mannitol 10g, sodium lauryl sulphate 10g, chloroform 100ml.
Ceramide is added in the round-bottomed flask of 1000mL, adds chloroform it is dissolved, put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make lipid become thin film in the round-bottomed flask bottom, subsequent use; Water with 800ml dissolves vitamin C, sodium lauryl sulphate, sucrose and mannitol, filters, and filtrating is poured in the above-mentioned flask; Hydration, the vibration, moisturizing with mixeding liquid volume to 1000mL; Through homogenization processing (16000psi, 3 times), obtain liposome turbid liquor; Spray drying promptly gets vitamin C precursor liposome.
Embodiment 12:
Vitamin C 100g, soybean lecithin 50g, Brij52 50g, mannitol 50g.
Soybean lecithin, Brij52 are added in the conical flask, and (chloroform: dissolving ethanol=1: 1) places 80 ℃ of waters bath with thermostatic control subsequent use to add chloroform and alcoholic acid mixed solution; , filter mannitol, vitamin C dissolving with 800mL water, the water-bath of will filtrating is heated to and the lipid soln uniform temp; The vibration of aqueous solution and lipid soln is mixed, cools off, moisturizing with mixeding liquid volume to 1000mL; Through homogenization processing (14000psi, 5 times), obtain liposome turbid liquor; Spray-dried, promptly get vitamin C precursor liposome.
Embodiment 13:
Vitamin C 100g, soybean lecithin 50g, sodium cholate 25g, sucrose 10g.
Soybean lecithin and sodium cholate are scattered in the water of 300ml in 75 ℃ of water-baths, subsequent use; With sucrose and vitamin C dissolving, be heated to 75 ℃ with 500ml water; Both are mixed, vibration, cooling, water is mended to 1000mL, through homogenization processing (18000psi, 3 times), obtains liposome turbid liquor, through lyophilization (temperature-50 ℃, vacuum 70mtorr), vitamin C precursor liposome.
Embodiment 14:
Vitamin C 100g, ceramide 25g, Brij52 50g, sodium cholate 25g sucrose 20g.
Ceramide, Brij52 are added in the conical flask, and heating and melting places 80 ℃ of waters bath with thermostatic control subsequent use; , filter sucrose, vitamin C and sodium cholate dissolving with 800mL water, the water-bath of will filtrating is heated to and the lipid soln uniform temp; Aqueous solution is mixed with the lipid soln vibration, cooling, water mends mixeding liquid volume to 1000mL; Through homogenization processing (10000psi, 2 times), obtain liposome turbid liquor; Spray-dried, get vitamin C precursor liposome.
Embodiment 15:
Vitamin C 200g, ceramide 50g, Brij52 50g, cholesterol 25g, mannitol 25g, chloroform 200mL.
Ceramide, Brij52 and cholesterol are added in the 1000mL round-bottomed flask, add chloroform it is dissolved, put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make lipid become thin film in the round-bottomed flask bottom, subsequent use; Water with 800ml dissolves vitamin C, mannitol, filters, and filtrating is poured in the above-mentioned flask into hydration; Vibration, water mends mixeding liquid volume to 1000mL, through homogenization processing (10000psi, 4 times); Obtain liposome turbid liquor, spray drying gets vitamin C precursor liposome.
Embodiment 16:
Vitamin C 0.1g, soybean lecithin 25g, cholesterol 15g, ceramide 10g, sucrose 50g, 200mL chloroform.
Soybean lecithin, ceramide and cholesterol are added in the 1000mL round-bottomed flask, add chloroform it is dissolved, put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make lipid become thin film in the round-bottomed flask bottom, subsequent use; , filter vitamin C, sucrose dissolved with the water of 800ml, filtrating is poured in the above-mentioned flask into hydration; Vibration, water mends mixeding liquid volume to 1000mL, through homogenization processing (13000psi, 4 times); Obtain liposome turbid liquor, spray drying gets vitamin C precursor liposome.
Embodiment 17:
Vitamin C 1g, Ovum Gallus domesticus Flavus lecithin 25g, the solid sodium 15g of deoxidation gallbladder, sitosterol 10g, lactose 50g, 100mL chloroform.
Ovum Gallus domesticus Flavus lecithin, sodium deoxycholate and sitosterol are added in the 1000mL round-bottomed flask, add chloroform it is dissolved, put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make lipid become thin film in the round-bottomed flask bottom, subsequent use; Water with 800ml dissolves vitamin C, lactose, filters, and filtrating is poured in the above-mentioned flask into hydration; Vibration, water mends mixeding liquid volume to 1000mL, through homogenization processing (15000psi, 2 times); Obtain liposome turbid liquor, spray drying gets vitamin C precursor liposome.
Embodiment 18:
Vitamin C 10g, soybean lecithin 25g, Brij52 15g, stigmasterol 10g, mannitol 40g.
Soybean lecithin, Brij52 and stigmasterol are added in the conical flask, add an amount of ethanol heating for dissolving, place 80 ℃ of waters bath with thermostatic control subsequent use., filter mannitol, vitamin C dissolving with 800mL water, the water-bath of will filtrating is heated to and the lipid soln uniform temp; Aqueous solution is mixed with the lipid soln vibration, cooling, water mends mixeding liquid volume to 1000mL; Through homogenization processing (12000psi, 5 times), obtain liposome turbid liquor; Spray-dried, promptly get vitamin C precursor liposome.
Embodiment 19:
Vitamin C 50g, ceramide 15g, Brij52 15g, glucose 20g.
Ceramide, the Brij52 of recipe quantity are added in the conical flask, and heating and melting places 80 ℃ of waters bath with thermostatic control subsequent use.With of glucose, the vitamin C dissolving of 800mL water with recipe quantity, to filter, the water-bath of will filtrating is heated to and the lipid soln uniform temp; Aqueous solution is mixed with the lipid soln vibration, cooling, water mends mixeding liquid volume to 1000mL; Through homogenization processing (10000psi, 3 times), obtain liposome turbid liquor; Spray-dried, promptly get vitamin C precursor liposome.
Embodiment 20:
Vitamin C 80g, soybean lecithin 15g, cholesterol 3g, mannitol 2g, chloroform 50mL.
Soybean lecithin, cholesterol are added in the 1000mL round-bottomed flask, add chloroform it is dissolved, put rotating thin film evaporation in 25~40 ℃ of waters bath with thermostatic control, make lipid become thin film in the round-bottomed flask bottom, subsequent use; Water with 800ml dissolves vitamin C, mannitol, filters, and filtrating is poured in the above-mentioned flask into hydration; Vibration, water mends mixeding liquid volume to 1000mL, through homogenization processing (15000psi, 2 times); Obtain liposome turbid liquor, spray drying promptly gets vitamin C precursor liposome.
The vitamin C precursor liposome stability experiment
Vitamin C precursor liposome is by embodiment 13 preparations, and experiment divides three groups, is respectively vitamin C precursor liposome group, vitamin C liposome group and vitamin C aqueous solution group, in 25 ℃ of temperature, relative humidity 75% condition held.On 6 days same day to the of placing, respectively organize ascorbic content with high effective liquid chromatography for measuring every day respectively, is 100% with the 1st day Vitamin C content; With other each time medicament contg by comparison; Draw medicament contg and change percentage rate, every group is repeated three batches, and average result is seen table 1:
Table 1. vitamin C stability in aqueous solution, pro-liposome and liposome compares n=3
Figure G2009100455133D00091
Visible by table 1; Ascorbic stability order is pro-liposome>liposome>aqueous solution in three kinds of samples; And Vitamin C content obviously reduces in aqueous solution and liposome in time; And in vitamin C precursor liposome, change not quite, explain that vitamin C precursor liposome can obviously improve ascorbic stability.

Claims (2)

1. vitamin C precursor liposome, it is made by following method:
Vitamin C 100g, soybean lecithin 50g, sodium cholate 25g, sucrose 10g;
Soybean lecithin and sodium cholate are scattered in the water of 300ml in 75 ℃ of water-baths, subsequent use; With sucrose and vitamin C dissolving, be heated to 75 ℃ with 500ml water; Both are mixed, vibration, cooling, water is mended to 1000ml, through homogenization processing, 18000psi, 3 times, obtain liposome turbid liquor, through lyophilization, temperature-50 ℃, vacuum 70mtorr, vitamin C precursor liposome.
2. the application of the described vitamin C precursor liposome of claim 1 in preparation percutaneous drug administration preparation or cosmetics.
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