CN102600043A - Method for manufacturing S/O type suspension - Google Patents
Method for manufacturing S/O type suspension Download PDFInfo
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- CN102600043A CN102600043A CN2011104185338A CN201110418533A CN102600043A CN 102600043 A CN102600043 A CN 102600043A CN 2011104185338 A CN2011104185338 A CN 2011104185338A CN 201110418533 A CN201110418533 A CN 201110418533A CN 102600043 A CN102600043 A CN 102600043A
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- activating agent
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Abstract
The invention provides a method for manufacturing an S/O type suspension, which is large in oil phase selection range and easy to improve water-soluble solid medicament without removing organic solvents. The method is characterized by comprising a mixing step (S2), wherein a water-soluble solid medicament, a first surfactant and a second surfactant are mixed and the second surfactant has a greater HLB value than that of the first surfactant; a complex step (S3), wherein water obtained in the mixing step is removed so as to obtain a water-soluble solid medicament-surfactant composite; and a dispersing step (s4), wherein the water-soluble solid medicament-surfactant composite is dispersed into oil to form an S/O type suspension.
Description
Technical field
The microgranule that the present invention relates to a kind of water-soluble solid is evenly dispersed in the manufacturing approach of the S/O type suspension that is suspended state in the oil phase, applicable to the cosmetics of smearing skin, ointment and oral medicine etc.
Background technology
At present, as a kind of new formulation of water-soluble solid medicament, gazed at lipophilic surfactant coating water-soluble solid medicament and with its preparation that is dispersed in the S/O type suspension in the oil.This preparation of being processed by S/O type suspension has improved the absorption of skin because the water-soluble solid medicament is enclosed in the oil phase, again it is processed O/W type emulsion medicament and external environment isolation are protected.In addition, if use vegetable oil as oil phase, the lipase that oil can be existed in the small intestinal decomposes, can sustained release.
Therefore, developed the manufacturing approach of various S/O type suspensions.
For example can enumerate out: have aqueous solution with solid chemicals to be dispersed in and process the w/o type emulsion in the oil phase that is dissolved with surfactant, from this w/o type emulsion, remove moisture again and process the method for S/O type suspension (patent documentation 1); There is aqueous solution with solid chemicals to be dispersed in and processes the w/o type emulsion in the organic solvent that is dissolved with surfactant; After from this w/o type emulsion, removing moisture and organic solvent again, make it be dispersed in method (patent documentation 2) of processing S/O type suspension in the oiliness composition etc.
The prior art document
Patent documentation
Patent documentation 1: No. 4349639 communique of Japan Patent
Patent documentation 2: No. 4426749 communique of Japan Patent
Summary of the invention
But, in above-mentioned patent documentation 1, in the manufacturing approach of the S/O type suspension of record,, need to select to be dissolved in the surfactant of oil phase for the aqueous solution that makes solid chemicals is distributed in the oil phase.Therefore, as the manufacturing approach shortage versatility of S/O type suspension, can not freely select oil phase.For example,, desire goes though being dissolved into the emulsifying agent four glycerol condensation ricinoleate esters of record in the above-mentioned patent 1 in the squalane as oil phase, owing to do not dissolve, so such combination can not obtain S/O type suspension.
In addition; Owing to being removes the method that moisture is processed S/O type suspension after forming the w/o type emulsion for the time being; Therefore exist the capacity of w/o type emulsion to increase, energy-output ratio increases, and if the concentration of aqueous solution that does not reduce the water-soluble solid medicament problem that then particle diameter of dispersed particle does not diminish in the S/O type suspension.In other words, when the capacity of feeding intake is a certain amount of on making, there is the problem of the treating capacity minimizing of water-soluble solid material each time.Therefore,, then need repeat the manufacturing process of S/O type suspension for several times in order to improve the ratio of the water-soluble solid medicament in the S/O type suspension, exist to make take time and energy, labour and need the problem of mass energy.
Have again; The S/O type suspension manufacturing approach of record in the above-mentioned patent documentation 2; Owing to be that aqueous solution with solid chemicals is distributed to and processes the w/o type emulsion in the organic solvent that is dissolved with surfactant; After from this w/o type emulsion, removing moisture and organic solvent again, make it be distributed to the manufacturing approach of processing S/O type suspension in the oiliness composition, organic solvent is indispensable.Afterwards, because subsequent processing needs to contain the cryodesiccated operation of solution of organic solvent, there be the damage and the problem of environment pollution caused of the freezer dryer that organic solvent evaporates causes.In addition, because of the organic solvent volatilization difficulty that absorbs in the surfactant, so organic solvent might remain in the S/O type suspension.
The present invention just in view of above-mentioned in the past truth and carry out, problem to be solved provide oil phase kind applicatory abundant, easily improve the concentration of water-soluble solid medicament, need not remove the manufacturing approach of S/O type suspension of the operation of organic solvent.
The characteristic of the manufacturing approach of S/O type suspension of the present invention is to have: with water-soluble solid medicament, water, first surface activating agent and the blended mixed processes of second surface activating agent with HLB value bigger than this first surface activating agent; From the resulting mixed liquor of this mixed processes, remove moisture and obtain the compounded chemical preface of the complex of water-soluble solid medicament-surfactant; Be distributed to the dispersion step that forms S/O type suspension in the oil phase with complex with this water-soluble solid medicament-surfactant.
The manufacturing approach of S/O type suspension of the present invention is: at first in mixed processes, water-soluble solid medicament, water, first surface activating agent and second surface activating agent with HLB value bigger than this first surface activating agent are mixed.Afterwards, as the compounded chemical preface, from the resulting mixed liquor of mixed processes, remove the complex that moisture obtains water-soluble solid medicament-surfactant.At last, as dispersion step, the complex of water-soluble solid medicament-surfactant is distributed to oil phase forms the S/O suspension.
Use the manufacturing approach of S/O type suspension of the present invention to obtain the reason of S/O type suspension easily, though as yet fully not clearly, can do following supposition.That is: the second surface activating agent of using in the mixed processes has the HLB value bigger than first surface activating agent (that is, the hydrophilic tendency is stronger than first surface activating agent).Therefore; As shown in Figure 1; Think that there is water-soluble solid medicament particle 11 in the center of complex 10 of water-soluble solid medicament-surfactant of obtaining in the compounded chemical preface; What its surface was formed with the strong second surface activating agent of hydrophilic tendency exists the many layers 12 of ratio, and what the outside that has the many layers of ratio of second surface activating agent was formed with the stronger first surface activating agent of lipophile tendency exists the many layers 13 of ratio.
Therefore, the complex of water-soluble solid medicament-surfactant is become easily to the dispersion of oil phase, the kind of the oil phase that can be suitable for becomes abundant.
In addition, in the mixed processes and compounded chemical preface of the complex of water-soluble solid medicament-surfactant, do not use oil phase, the moisture in the aqueous solution that only heats up in a steamer the dissolubility solid chemicals that anhydrates and first and second surfactant mixtures.Therefore; Can avoid shown in the patent documentation 2, remove moisture after the w/o type emulsion and form the problem that the method for S/O type suspension exists because of forming for the time being: make the coexistence of oiliness composition cause manufacturing capacity increaseizations, then can not make problems such as the particle diameter of dispersed particle diminishes because of having to as if the concentration of aqueous solution that does not reduce the water-soluble solid medicament.Therefore, in the not only disposable manufacturing treating capacity of water soluble medicament significantly efficient activity but also energy-output ratio also can reduce.
Have again, because the preparation of the complex of water-soluble solid medicament-surfactant is not with an organic solvent, the necessity of therefore not removing organic solvent.
Thereby according to the manufacturing approach of S/O type suspension of the present invention, the oil phase kind that can be suitable for becomes abundant, improves the concentration of water-soluble solid medicament easily, also need not remove the operation of organic solvent.
In the manufacturing approach of S/O type suspension of the present invention, first surface activating agent and/or the preferred nonionic surfactant of second surface activating agent.Nonionic surfactant is littler to the zest of human body than the ionic surfactant, and therefore, safety was good when the toiletries of water soluble medicament, oral agents etc. were used at the contact human body.
In addition, the HLB value of first surface activating agent is preferably below 4.According to inventor's of the present invention result of the test, if the HLB value of first surface activating agent is below 4, then the dispersion of the complex of water-soluble solid medicament-surfactant in oil phase becomes easy.Its reason as stated, supposition is that the surface owing to the outermost shell of the complex of water-soluble solid medicament-surfactant is to have many layer forming of ratio by the stronger first surface activating agent with little HLB value of lipophile tendency.The HLB value of further preferred first surface activating agent is below 3.5, most preferably to be below 3.0.
In addition, the HLB value of second surface activating agent is preferably more than 5 and less than 17.According to inventor's of the present invention result of the test, if the HLB value of second surface activating agent is more than 5 and less than 17, then the dispersion of the complex of water-soluble solid medicament-surfactant in oil phase becomes easy.Its reason as stated; Supposition be owing to the layer that contacts with the water-soluble solid medicament of the complex of water-soluble solid medicament-surfactant be by the stronger second surface activating agent of hydrophilic tendency with big HLB value have many layer forming of ratio, cause with the complex of water-soluble solid medicament firm.The HLB value of further preferred second surface activating agent is more than 6 and less than 16.5, most preferably is more than 6.5 and less than 16.
In addition, the fusing point of first surface activating agent and second surface activating agent is preferably below 30 ℃.Like this; Because the function as surfactant of first surface activating agent and second surface activating agent can be in performance below 30 ℃; So mixed processes, compounded chemical preface and dispersion step can be carried out under the temperature below 30 ℃; When preventing that the water-soluble solid medicament from changing because of heating, can reduce and make the needed energy resource consumption of S/O type suspension.
In addition, in the manufacturing approach of S/O type suspension of the present invention, as the water-soluble solid medicament, every solid chemicals that is dissolvable in water in the water all can suitably use.As such water-soluble solid medicament, can enumerate for example various water soluble medicaments such as water-soluble vitamins such as water soluble antioxidant, cyanocobalamin, water soluble protein, water-soluble antimicrobial, water-soluble anticancer agent, the agent of water solublity easing pain and diminishing inflammation such as ascorbic acid etc.This wherein, the water-soluble solid medicament is the L-magnesium L-ascorbyl-2-phosphate in this way, through it being processed S/O type suspension, the efficient of skin absorbs L-magnesium L-ascorbyl-2-phosphate is improved, and can improve whitening effect.
Manufacturing approach as S/O type suspension of the present invention; Particularly, can with the L-magnesium L-ascorbyl-2-phosphate as the water-soluble solid medicament, with sucrose five eruciates as the first surface activating agent, with polyoxyethylene sorbitol tetraoctyl stearate (30E.O.) or polyoxyethylene glycerol three isostearates (20E.O.) as the second surface activating agent.
Description of drawings
Fig. 1 is the sectional schematic diagram of the complex of water-soluble solid medicament-surfactant.
Fig. 2 is the process chart of the S/O type suspension manufacturing approach of embodiment.
Symbol description
10... water-soluble solid medicament-surfactant
11... water-soluble solid medicament particle
12,13... layer
20... oil phase
S1... dissolution process
S2... mixed processes
S3... compounded chemical preface
S4... dispersion step
The specific embodiment
Below embodiment of the present invention is described.
The manufacturing approach of the S/O type suspension of embodiment is carried out by following operation successively.
< dissolution process >
At first the water-soluble solid medicament is dissolved in and processes aqueous solution in the water.The every solid of water-soluble solid medicine and be water-soluble substances just can be done suitable selection according to purpose.For example can enumerate: the L-magnesium L-ascorbyl-2-phosphate that uses as whitening agent etc.In addition, the solvent as dissolving water-soluble solid medicine can make water, also can use the water that has added the pH buffer.
Solution concentration to does not at this moment have particular restriction, but considers the suitable selections such as concentration of water-soluble solid medicament to the dissolubility of water, S/O type suspension that desire is made.
< mixed processes >
Secondly, the second surface activating agent that adds above-mentioned aqueous solution, first surface activating agent and have a HLB value bigger than first surface activating agent mixes.Do not make particular restriction as mixed method, can enumerate the mechanical agitation of using propeller, and with hyperacoustic stirring, homogenizer (Homogenizer), homixerizer (Homomixer), kneading machine (Kneader) etc.About the kind of first surface activating agent and second surface activating agent, the HLB value of selecting the second surface activating agent is greater than first surface activating agent person.
In addition, first surface activating agent and the blended ratio of second surface activating agent do not separate into 2 phases and are uniformly dispersed and then do not make particular restriction as long as accomplish at mixed processes after back or compounded chemical preface are accomplished.
The preferred HLB value of first surface activating agent is below 4, is preferably below 3.5 especially, most preferably is below 3.0.
As the HLB value is the first surface activating agent below 4, specifically can enumerate: sucrose six eruciates, sucrose five eruciates, sucrose gather oleate, sucrose polyoxyethylene lauryl acid esters, diglycerol tetraoctyl stearate, four glycerol, five oleates, four glycerol condensation ricinoleate esters, six glycerol condensation ricinoleate esters, sorbitan trioleate, SY-Glyster DAO 750.Therefrom can use separately a kind of, also can be two or more mixing use.
In addition, second surface activating agent HLB value be preferably more than 5 and less than 17, especially be preferably more than 6 and less than 16.5, most preferably be more than 6.5 and less than 16.
As the HLB value is more than 5 and less than 17 second surface activating agent, specifically can enumerate: polyoxyethylene sorbitol tetraoctyl stearate, Polyoxyethylene sorbitol tetraoleate, polyoxyethylene sorbitan monolaurate, polyoxyethylene glycerol three isostearates, polyoxyethylene olein, polyethylene glycol monolaurate, polyethylene glycol monooleate, Polyethylene Glycol diisopstearate, polyoxyethylene oleyl ether, polyoxyethylene lauryl ether, polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene 20 sorbitan monooleate, polyoxyethylene 20 sorbitan monostearate, polyoxyethylene 20 sorbitan monolaurate, polyoxyethylene sorbitan isostearate, polyoxyethylene 20 sorbitan trioleate, polyglyceryl-isostearate, polyglycereol laurate and polyglycerol acrylate.Therefrom can use separately a kind of, also can be two or more mixing use.
In addition, the HLB value of first, second surfactant can be used calculating such as method on Atlas (ア ト ラ ス) method, Griffin (グ リ Off イ Application) method, Davis (デ イ PVC ス) method, the river.The computational methods of for example enumerating method on the river as follows as an example.
HLB＝7+11.7log(Mw/Mo)...(I)
Here, in formula (I), Mw representes the molecular weight of hydrophilic radical part, and Mo representes the molecular weight of lipophile group part.
< compounded chemical preface >
Afterwards, from the mixed liquor that mixed processes obtains, remove and anhydrate, obtain the complex of water-soluble solid medicament-surfactant.As the method for removing of water, the freeze-drying under decompression, can also enumerate heating or the decompression method of heating down.If use the freeze-drying under the decompression, then can be used in heat stability low water-soluble solid medicament, surfactant, therefore preferred.
< dispersion step >
At last, the complex of water-soluble solid medicament-surfactant is distributed in the oil phase and obtains S/O type suspension.This process for dispersing there is not particular determination; Can use the mechanicalness stirring that utilizes propeller, homogenizer (Homogenizer), homixerizer (Homomixer), kneading machine (Kneader) etc. in emulsifying, normally used method etc. when disperseing; And then can use separately or and use ultrasound wave, perhaps also can heat.
In addition, the oiliness composition that oil phase uses does not have particular restriction, can suitably select according to purpose.For example, can use soybean oil, olive oil, Jojoba wet goods vegetable oil, animal oil such as fish oil, Hydrocarbon such as liquid paraffin, squalane, MCT Oil etc. in addition, also can mix these compositions and use.
In addition, can add oil loving viscosifier as required in the oil phase.Thus, the viscosity increase because of oil phase can obtain the S/O type suspension as the gelatine preparation.
In the manufacturing approach of S/O type suspension of the present invention, in not hindering the scope of accomplishing the invention problem, can add accessory additive as required to carry out all upgradings.As the example of accessory additive, can enumerate antioxidant, preservative agent, viscosifier, spice, coloring agent, pigment, antibacterial, stabilizing agent etc.
Embodiment
Below, illustrating in greater detail the present invention through embodiment, the present invention not only is defined in these embodiment.
(embodiment 1-1～1-4)
< dissolution process >
To be dissolved in as L-magnesium L-ascorbyl-2-phosphate (the following APM that abbreviates as the sometimes) 0.5g of water-soluble solid medicament among the Purified Water 9.5g and obtained the APM aqueous solution.
< mixed processes >
Secondly; Weighing is as the sucrose five eruciate 4.75g of first surface activating agent with as polyoxyethylene sorbitol tetraoctyl stearate (30E.O.) 4.75g of second surface activating agent; Add above-mentioned APM aqueous solution, fully stir, make its homodisperse and process mixed liquor.In addition, the HLB value of sucrose five eruciates is 2, and the HLB value of polyoxyethylene sorbitol tetraoctyl stearate (30E.O.) is 11.1.
< compounded chemical preface >
With the mixed liquor lyophilization that obtains in the above-mentioned mixed processes, obtain having the complex of the liquid A PM-surfactant of viscosity.
< dispersion step >
The complex 1.0g of the above-mentioned APM-surfactant of weighing; To wherein add oil (be soybean oil 99g in embodiment 1-1, in embodiment 1-2 for squalane 99g, in embodiment 1-3, be squalane: the miscella 99g of Jojoba oil=8: 2 (mass ratio), in embodiment 1-4, be squalane: the miscella 99g of Jojoba oil=8: 2 (mass ratio) and micro-vitamin E and spice); Ultrasound wave limit medication spoon (spatula) mixing is carried out on the limit, obtains the S/O type suspension of embodiment 1-1～1-4.
In addition, do not add the second surface activating agent in the comparative example 1, added sucrose five eruciate 9.5g as the first surface activating agent.Comparative example 2 does not add the first surface activating agent, has added polyoxyethylene sorbitol tetraoctyl stearate (30E.O.) 9.5g as the second surface activating agent.
Composition and the composition of comparative example 1 of having represented the S/O type suspension of embodiment 1-1～1-4 and comparative example 2 in the table 1.
[table 1]
The APM:L-magnesium L-ascorbyl-2-phosphate
PES: sucrose five eruciates, HLB 2
TPS: polyoxyethylene sorbitol tetraoctyl stearate (30E.O.), HLB 11.1
The S/O type suspension of the embodiment 1-1～1-4 that obtains like this is faint yellow (color of soybean oil), almost transparent in this way during soybean oil, other the time be colourless almost transparent, detect by an unaided eye during through 5 days after the preparation and do not find the variation of outward appearance.In addition, with the S/O type suspension particle diameter of dynamic light scattering determination embodiment 1-2, the result approximately is 200 nanometers.
In contrast to this, the prepared product of comparative example 1 causes the preparation section of failing to proceed to S/O type suspension because of in mixed process, two being separated and not processing uniform mixture.In addition, the S/O type suspension of comparative example 2 has had precipitate to separate out during through 4 days after preparation.
(embodiment 2-1～2-5)
The S/O type suspension that in embodiment 2-1～2-5, has prepared the composition of below table 2.Method for preparing is omitted explanation as embodiment 1-1～1-4 at this.These S/O type suspensions are colourless and almost transparent, detect by an unaided eye during through 5 days after the preparation and do not find the variation of outward appearance.
[table 2]
The APM:L-magnesium L-ascorbyl-2-phosphate
PES: sucrose five eruciates, HLB 2
TPS: polyoxyethylene sorbitol tetraoctyl stearate (30E.O.), HLB 11.1
(embodiment 3-1～3-3)
The S/O type suspension that in embodiment 3-1～3-3, has prepared the composition of below table 3.Method for preparing is omitted explanation as embodiment 1-1～1-4 at this.These S/O type suspensions are faint yellow and almost transparent during soybean oil in this way, other the time be colourless and almost transparent, detect by an unaided eye during through 5 days after the preparation and do not find the variation of outward appearance.
[table 3]
The APM:L-magnesium L-ascorbyl-2-phosphate
PES: sucrose five eruciates, HLB 2
TPG: polyoxyethylene glycerol three isostearates (20E.O.), HLB 10.4
(embodiment 4-1～4-2)
The S/O type suspension that in embodiment 4-1～4-2, has prepared the composition of below table 4.Method for preparing is omitted explanation as embodiment 1-1～1-4 at this.These S/O type suspensions are faint yellow and almost transparent, detect by an unaided eye during through 5 days after the preparation and do not find the variation of outward appearance.
[table 4]
The APM:L-magnesium L-ascorbyl-2-phosphate
TGR: four glycerol condensation ricinoleate esters, HLB 2
HGR: six glycerol condensation ricinoleate esters, HLB 0.6
TPS: polyoxyethylene sorbitol tetraoctyl stearate (30E.O.), HLB 11.1
(embodiment 5-1～5-2)
The S/O type suspension that in embodiment 5-1～5-2, has prepared the composition of below table 5.Method for preparing is omitted explanation as embodiment 1-1～1-4 at this.In addition, comparative example 3 does not add the first surface activating agent, has added polyoxyethylene hydrogenated Oleum Ricini (10E.O.) 9.5g as the second surface activating agent.The S/O type suspension of the embodiment 5-1～5-2 that obtains like this is faint yellow and almost transparent, detects by an unaided eye during through 5 days after the preparation and does not find the variation of outward appearance.In contrast to this, the S/O type suspension of comparative example 3 was separated out deposition after 1 day.
[table 5]
The APM:L-magnesium L-ascorbyl-2-phosphate
HGR: six glycerol condensation ricinoleate esters, HLB 0.6
TGR: four glycerol condensation ricinoleate esters, HLB 2
HCO-10: polyoxyethylene hydrogenated Oleum Ricini (10E.O.), HLB 6.5
(embodiment 6)
The S/O type suspension that in embodiment 6, has prepared the composition of below table 6.Method for preparing is omitted explanation as embodiment 1-1～1-4 at this.It is transparent that this S/O type suspension is pink colour, detects by an unaided eye during through 5 days after the preparation and do not find the variation of outward appearance.
[table 6]
VB12: cyanocobalamin
HGR: six glycerol condensation ricinoleate esters, HLB 0.6
Polyoxyethylene Sorbitan Monooleate: polyoxyethylene 20 sorbitan monooleate (20E.O.), HLB 15.0
The present invention does not receive any restriction of above-mentioned embodiment and embodiment explanation.All modes of texturing in not breaking away from the scope put down in writing in claims, scope that those skilled in the art expect easily include in the present invention.
Utilize probability on the industry
The present invention can absorb or the manufacturing of the S/O type suspension of oral water soluble medicament is used well through skin being used for.
Claims (10)
1. the manufacturing approach of a S/O type suspension is characterized in that having:
With water-soluble solid medicament, water, first surface activating agent and the blended mixed processes of second surface activating agent with HLB value bigger than this first surface activating agent;
From the resulting mixed liquor of this mixed processes, remove moisture and obtain the compounded chemical preface of the complex of water-soluble solid medicament-surfactant; And
The complex of this water-soluble solid medicament-surfactant is distributed to the dispersion step that forms S/O type suspension in the oil phase.
2. the manufacturing approach of S/O type suspension as claimed in claim 1 is characterized in that, said first surface activating agent and/or said second surface activating agent are nonionic surfactant.
3. according to claim 1 or claim 2 the manufacturing approach of S/O type suspension is characterized in that the HLB value of said first surface activating agent is below 4.
4. like the manufacturing approach of each described S/O type suspension in the claim 1～3; It is characterized in that said first surface activating agent more than one for selecting the group of gathering oleate, sucrose polyoxyethylene lauryl acid esters, diglycerol tetraoctyl stearate, four glycerol, five oleates, four glycerol condensation ricinoleate esters, six glycerol condensation ricinoleate esters, sorbitan trioleate, SY-Glyster DAO 750 from sucrose six eruciates, sucrose five eruciates, sucrose and forming.
5. like the manufacturing approach of each described S/O type suspension in the claim 1～4, it is characterized in that the HLB value of said second surface activating agent is more than 5 and less than 17.
6. like the manufacturing approach of each described S/O type suspension in the claim 1～5; It is characterized in that said second surface activating agent is more than one that from the group that polyoxyethylene sorbitol tetraoctyl stearate, Polyoxyethylene sorbitol tetraoleate, polyoxyethylene sorbitan monolaurate, polyoxyethylene glycerol three isostearates, polyoxyethylene olein, polyethylene glycol monolaurate, polyethylene glycol monooleate, Polyethylene Glycol diisopstearate, polyoxyethylene oleyl ether, polyoxyethylene lauryl ether, polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene 20 sorbitan monooleate, polyoxyethylene 20 sorbitan monostearate, polyoxyethylene 20 sorbitan monolaurate, polyoxyethylene sorbitan isostearate, polyoxyethylene 20 sorbitan trioleate, polyglyceryl-isostearate, polyglycereol laurate and polyglycerol acrylate are formed, select.
7. like the manufacturing approach of each described S/O type suspension in the claim 1～6, it is characterized in that the fusing point of said first surface activating agent and said second surface activating agent is below 30 ℃.
8. like the manufacturing approach of each described S/O type suspension in the claim 1～7, it is characterized in that said water-soluble solid medicament is the L-magnesium L-ascorbyl-2-phosphate.
9. like the manufacturing approach of each described S/O type suspension in the claim 1～8; It is characterized in that; Said water-soluble solid medicament is the L-magnesium L-ascorbyl-2-phosphate; Said first surface activating agent is sucrose five eruciates, and said second surface activating agent is polyoxyethylene sorbitol tetraoctyl stearate (30E.O.).
10. like the manufacturing approach of each described S/O type suspension in the claim 1～8; It is characterized in that; Said water-soluble solid medicament is the L-magnesium L-ascorbyl-2-phosphate; Said first surface activating agent is sucrose five eruciates, and said second surface activating agent is polyoxyethylene glycerol three isostearates (20E.O.).
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| CN101022785A (en) * | 2004-08-31 | 2007-08-22 | 亚斯比恩股份有限公司 | External preparation of s/o type |
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| JP2006176469A (en) * | 2004-12-24 | 2006-07-06 | Kao Corp | Oily cleanser |
| JP2008260736A (en) * | 2007-04-13 | 2008-10-30 | Dai Ichi Kogyo Seiyaku Co Ltd | Oil-based solid cosmetic |
| JP5442937B2 (en) * | 2007-04-20 | 2014-03-19 | ロレアル | Topical preparation |
| EP2216015A4 (en) * | 2007-11-02 | 2012-12-19 | So Pharmaceutical Corp | Poorly soluble substance-surfactant complex product, and process for production thereof |
| WO2009139506A1 (en) * | 2008-05-15 | 2009-11-19 | Ａｓｐｉｏｎ株式会社 | Combination of drugs having different physical properties into single dosage form |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1732903A (en) * | 2004-08-10 | 2006-02-15 | 上海华谊生物技术有限公司 | Method for preparing sustained-release miniball |
| CN101022785A (en) * | 2004-08-31 | 2007-08-22 | 亚斯比恩股份有限公司 | External preparation of s/o type |
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Application publication date: 20120725 |