CN113876943A - Concentrated oil-in-water type submicron emulsion adjuvant and preparation method thereof - Google Patents

Concentrated oil-in-water type submicron emulsion adjuvant and preparation method thereof Download PDF

Info

Publication number
CN113876943A
CN113876943A CN202010631457.8A CN202010631457A CN113876943A CN 113876943 A CN113876943 A CN 113876943A CN 202010631457 A CN202010631457 A CN 202010631457A CN 113876943 A CN113876943 A CN 113876943A
Authority
CN
China
Prior art keywords
oil
adjuvant
squalene
buffer
span
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
Application number
CN202010631457.8A
Other languages
Chinese (zh)
Inventor
谢良志
张延静
张建东
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sinocelltech Ltd
Original Assignee
Sinocelltech Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Sinocelltech Ltd filed Critical Sinocelltech Ltd
Priority to CN202010631457.8A priority Critical patent/CN113876943A/en
Publication of CN113876943A publication Critical patent/CN113876943A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59

Abstract

The invention belongs to the field of oil-in-water emulsion adjuvants of vaccines, and relates to a concentrated oil-in-water type submicron emulsion adjuvant and a preparation method thereof. In a preferred technical scheme, the submicron emulsion adjuvant is MF59 with 2, 3, 4,6 and 8 times concentration. The prepared concentrated microemulsion adjuvant is relatively stable, the particle size of the adjuvant is slightly influenced by the preparation concentration, and the concentrated microemulsion adjuvant can be used as a vaccine adjuvant. When in use, the water can be diluted according to requirements, so that the utilization rate of equipment is improved, and the production cost is reduced.

Description

Concentrated oil-in-water type submicron emulsion adjuvant and preparation method thereof
Technical Field
The present invention relates to the field of oil-in-water emulsion adjuvants, for example for the preparation of vaccines, and in particular to the preparation of concentrated oil-in-water type submicroemulsion adjuvants and methods for their preparation.
Technical Field
Vaccine adjuvant MF59 was a submicron oil-in-water emulsion of squalene, polysorbate 80 (also known as tween 80) and sorbitan trioleate (also known as span 85). It may also contain citrate ions, such as 10mM sodium citrate buffer.
Chinese patents CN102740832B and CN102858322B disclose that the composition of the emulsion by volume can be about 5% squalene, about 0.5% tween 80 and about 0.5% span 85, and further comprises 10mM sodium citrate buffer. And provides an improved process for the preparation of microfluidised oil-in-water emulsions (eg MF59), particularly suitable for use on a commercial scale and using filtration. Wherein CN102740832B provides a device for preparing a microfluidised oil-in-water emulsion: comprising an interaction chamber comprising a plurality of Z-shaped channels and an auxiliary process module comprising at least one channel, wherein the auxiliary process module is located downstream of the interaction chamber.
In industrial production, the utilization rate of equipment is extremely important, and the concentrated emulsion adjuvant means reduced production cost and saved storage space.
Disclosure of Invention
The present invention provides a method for preparing a concentrated oil-in-water type submicroemulsion adjuvant, wherein the method comprises the steps of:
i) preparing a first emulsion having a first average oil droplet size, and
ii) microfluidizing the first emulsion to form a second emulsion having a second average oil droplet size smaller than the first average oil droplet size,
wherein the oil content in the submicroemulsion adjuvant is 5-50% v/w (excluding 5%), preferably
The oil content was 10%, 15%, 20%, 30% and 40% (v/w).
In one embodiment of the present invention, the substrate is,
(ii) the pressure of (a) is 500-1400bar, the number of microfluidization is 2-9 and the cooling water temperature is 7-25 ℃.
In one embodiment of the invention, the concentrated oil-in-water submicron emulsion adjuvant comprises an oil, a surfactant, a buffer and water.
In one embodiment of the present invention, the substrate is,
the oil is selected from one or more of peanut oil, soybean oil, coconut oil, olive oil, jojoba oil, safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil, corn oil, cod liver oil, whale oil, tocopherol, and squalene;
the surfactant is selected from polyoxyethylene sorbitan ester surfactant (tween), phospholipid, polyoxyethylene fatty ether derived from dodecanol, hexadecanol, octadecanol and oleyl alcohol (brij surfactant), polyoxyethylene-9-lauryl ether and sorbitan ester (span); preferably, one or more of polysorbate 20, polysorbate 80, phosphatidylcholine (lecithin), bezoar 30, span 85;
the buffer is selected from: citric acid buffer, phosphate buffer, Tris buffer, borate buffer, succinate buffer, histidine buffer;
in one embodiment of the invention, the weight ratio of squalene, span 85, polysorbate 80 is about 12.9:1.5: 1.5; and the squalene content of the oil phase and water phase mixture finally formed is 5-50% v/w (excluding 5%), preferably the squalene content of the oil phase and water phase mixture is 10%, 15%, 20%, 30% and 40%.
In one embodiment of the invention, the concentrated oil-in-water submicron emulsion adjuvant comprises squalene, span 85, polysorbate 80 and citric acid buffer, wherein the weight ratio of squalene, span 85, polysorbate 80 is about 12.9:1.5: 1.5; and a citric acid buffer concentration of 10 mM; wherein the content of squalene is 5-50% v/w (excluding 5%), i.e. the submicroemulsion adjuvant is MF59 with N times concentration, N is a number of 1-10, excluding 1; preferably, the content of squalene in the sub-microemulsion adjuvant is 10%, 15%, 20%, 30% and 40% (v/w), i.e. 2, 3, 4,6, 8 times the concentration of MF 59.
These concentrated oil-in-water type submicron emulsion adjuvants can be diluted as desired at the time of use.
In one embodiment of the invention, the particle size of the oil droplets in the submicron emulsion adjuvant is 140-190nm, preferably 150-180 nm. The particle size of the concentrated adjuvant did not change when placed at 37 ℃ for one week, indicating that the adjuvant was relatively stable. The particle size of the sub-microemulsion adjuvant is slightly influenced by the preparation concentration.
Drawings
FIG. 1 shows the particle size and the index of particle size distribution of oil-in-water type submicron emulsion adjuvant with different concentrations.
FIG. 2 Zeta potentials for preparing different concentrations of oil-in-water submicroemulsion adjuvant.
Detailed Description
Example 1: preparation of oil-in-water type submicron emulsion adjuvant
1.1 the liquid preparation process is as follows:
(1) preparing an oil phase: span 85(Span 85) was weighed out as in table 1 and dissolved in squalene.
(2) Preparing a water phase: polysorbate 80(Tween 80), citric acid, sodium citrate were weighed out in Table 1 and dissolved in water.
(3) The oil phase was added to the aqueous phase.
1.2 preparation of crude milk
Coarse milk was prepared by dispersing for 3 minutes at a set rotation speed of 15000rpm using a high-speed disperser (XHF-DY, Ningbo Xinzhi Biotech Co., Ltd.) of stator-rotor structure.
1.3 submicron emulsion preparation
The crude milk was poured into the feed bowl of a microfluidizer (ATS, AMH-15), the homogenization pressure was set according to Table 1, and the cooling water temperature was set. Homogenization is started and the homogenized emulsion is collected from the outlet. After the feeding trough is emptied, the homogenized emulsion is poured into the feeding trough for the second homogenization, and the number of homogenization cycles is shown in table 1. The final emulsion is the oil-in-water type submicron emulsion adjuvant.
1.4 measurement of particle diameter
The sample was diluted with water 5000-100000 times to ensure a squalene content of 0.001% (v/v) at the final concentration, and the particle size distribution of the emulsion were measured using a dynamic laser light scattering apparatus (DynaPro Plate Reader-II), and the results are shown in Table 1.
1.5 measurement of Zeta potential
Samples of 4,6,10,22 were diluted 200-fold with water and the Zeta potential was measured using a malvern particle size Zeta potentiostat (Malven ZEN2600) and the results are shown in table 2 and fig. 2.
TABLE 1. different oil-in-water emulsion ratios and process parameters and particle size of the emulsions prepared
Figure BDA0002568974240000031
TABLE 2 Zeta potential of emulsions prepared at different squalene concentrations
Figure BDA0002568974240000032
Based on a formulation containing 20% (v/w) squalene adjuvant (17.2% w/w squalene, 2% w/w span 85 and 2% w/w polysorbate 80), under the conditions of cooling temperature of 25 ℃ and homogenization for 4 times, the particle size of the stock solution under the pressure of 500-1400bar is researched, and the higher the homogenization pressure is, the lower the particle size of the stock solution is. When the homogenizing pressure is increased from 500 to 1400bar, the particle size is reduced by about 20nm, and the particle distribution is relatively concentrated at 800-1100 bar.
Based on a formulation containing 20% (v/w) squalene adjuvant (17.2% w/w squalene, 2% w/w span 85 and 2% w/w polysorbate 80), the influence of the homogenization frequency on the quality of the stock solution is examined under the conditions of a cooling temperature of 25 ℃ and a homogenization pressure of 1100 bar. The results show that the number of homogenizations has less influence on the particle size.
Based on a formulation containing 20% (v/w) squalene adjuvant (17.2% w/w squalene, 2% w/w span 85 and 2% w/w polysorbate 80), the influence of the cooling water temperature on the particle size is examined under the conditions of a homogenization pressure of 1100bar and 4 times of homogenization, and the result shows that the influence of the cooling water temperature on the particle size is little.
When the concentrations of span 85 and polysorbate 80 are unchanged, the weight ratio of squalene to the original solution is reduced, the particle size of the original solution is reduced, and the particle size distribution is not obviously related to the squalene concentration.
Under the condition of keeping the proportions of squalene, span 85 and polysorbate 80 unchanged, the influence of the numbers 4,6,10 and 22 of the experimental samples with different concentrations on the particle size is examined under the experimental conditions of the homogenizing pressure of 1000bar, the homogenizing time of 4 times and the cooling water temperature of 25 ℃, the result is shown in figure 1, the particle size of the emulsion is not changed greatly within the range of the squalene concentration of 5-40% (v/w), and the influence of the concentration for preparing the emulsion on the particle size is small. As the concentration is increased, the PDI of the microemulsion is reduced, which indicates that the particle size of the emulsion prepared by concentration is more uniform.
As is clear from the results in Table 2 and FIG. 2, the Zeta potential of the emulsions prepared at different concentrations did not change much.
Example 2: stability study of oil-in-water type submicron emulsion adjuvant
An adjuvant having a squalene concentration of 20% (v/w) and 40% (v/w) was prepared according to example 1, and placed in an incubator at 37 ℃ for one week under a closed condition. The particle size of the emulsion at the start and after the end of the standing was measured according to example 1.4, and the results are shown in Table 3. As can be seen, the particle size did not change when the adjuvant was left at 37 ℃ for 7 days.
TABLE 3 particle size of emulsions prepared at different squalene concentrations after standing at 37 ℃
Figure BDA0002568974240000041
In conclusion, the particle size of the microemulsion adjuvant is slightly affected by the preparation concentration. In order to improve the utilization rate of equipment, reduce the production cost and save the storage space, concentrated emulsion adjuvant can be prepared and then diluted to proper concentration to prepare a preparation when in use.

Claims (8)

1. A method for preparing a concentrated oil-in-water type submicroemulsion adjuvant comprises
i) Preparing a first emulsion having a first average oil droplet size, and
ii) microfluidizing the first emulsion to form a second emulsion having a second average oil droplet size that is smaller than the first average oil droplet size;
wherein, the submicron emulsion adjuvant; the oil content is 5-50% v/w (excluding 5%), preferably
The oil content was 10%, 15%, 20%, 30% and 40% (v/w).
2. The method of claim 1, wherein
(ii) The pressure of (a) is 500-1400bar, the number of microfluidization is 2-9 and the cooling water temperature is 7-25 ℃.
3. The method of claim 1 or 2, wherein the sub-microemulsion adjuvant comprises an oil, a surfactant, a buffer, and water.
4. The method of any one of claims 1-3, wherein
The oil is selected from one or more of peanut oil, soybean oil, coconut oil, olive oil, jojoba oil, safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil, corn oil, cod liver oil, whale oil, tocopherol, and squalene;
the surfactant is selected from polyoxyethylene sorbitan ester surfactant (tween), phospholipid, polyoxyethylene fatty ether derived from dodecanol, hexadecanol, octadecanol and oleyl alcohol (brij surfactant), polyoxyethylene-9-lauryl ether and sorbitan ester (span); preferably, one or more of polysorbate 20, polysorbate 80, phosphatidylcholine (lecithin), bezoar 30, span 85;
the buffer is selected from citric acid buffer, phosphate buffer, Tris buffer, borate buffer, succinate buffer, histidine buffer.
5. The method of any one of claims 1 to 4,
wherein the submicroemulsion adjuvant comprises squalene, span 85, polysorbate 80 and citric acid buffer, wherein the weight ratio of squalene, span 85 and polysorbate 80 is about 12.9:1.5:1.5, and the concentration of citric acid buffer is 10 mM; and is
The content of squalene is 5-50% v/w (5% excluded);
preferably, the content of squalene in the sub-microemulsion adjuvant is 10%, 15%, 20%, 30% and 40% (v/w).
6. The method according to any one of claims 1-5, wherein the particle size of the oil droplets in the adjuvant is 140-190nm, preferably 150-180 nm.
7. A concentrated oil-in-water type submicron emulsion adjuvant,
it contains squalene, span 85, polysorbate 80 and citric acid buffer, wherein the weight ratio of squalene, span 85 and polysorbate 80 is about 12.9:1.5:1.5 and the concentration of citric acid buffer is 10 mM; and is
The content of squalene is 5-50% v/w (5% excluded),
preferably, the content of squalene in the sub-microemulsion adjuvant is 10%, 15%, 20%, 30% and 40% (v/w).
8. The sub-microemulsion adjuvant of claim 7, wherein the oil droplet in the sub-microemulsion adjuvant has a particle size of 140-190nm, preferably 150-180 nm.
CN202010631457.8A 2020-07-03 2020-07-03 Concentrated oil-in-water type submicron emulsion adjuvant and preparation method thereof Pending CN113876943A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010631457.8A CN113876943A (en) 2020-07-03 2020-07-03 Concentrated oil-in-water type submicron emulsion adjuvant and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010631457.8A CN113876943A (en) 2020-07-03 2020-07-03 Concentrated oil-in-water type submicron emulsion adjuvant and preparation method thereof

Publications (1)

Publication Number Publication Date
CN113876943A true CN113876943A (en) 2022-01-04

Family

ID=79013179

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010631457.8A Pending CN113876943A (en) 2020-07-03 2020-07-03 Concentrated oil-in-water type submicron emulsion adjuvant and preparation method thereof

Country Status (1)

Country Link
CN (1) CN113876943A (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102858322A (en) * 2009-12-03 2013-01-02 诺华有限公司 Hydrophilic filtration during manufacture of vaccine adjuvants

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102858322A (en) * 2009-12-03 2013-01-02 诺华有限公司 Hydrophilic filtration during manufacture of vaccine adjuvants

Similar Documents

Publication Publication Date Title
AU2016374436B2 (en) Oil-in-water type emulsion composition and method for producing same
CN1091591C (en) Lipophilic carrier preparations
CN109996551A (en) The method of selective extraction cannboid from plant source
CN104203205B (en) Transparency emulsification composition high and transparency cosmetic preparation high
SE504664C2 (en) Methods for preparing fractional oil, the oil, its use and emulsion composition containing the oil
CA2019710A1 (en) Process for the production of a nanoemulsion of oil particles in an aqueous phase
EP0100459A2 (en) An aqueous liquid containing a fat-soluble substance
CN103641195A (en) Organic silicon defoamer and preparation method thereof
KR100949848B1 (en) Nanoemulsion composition comprising Vitamin-C derivative and method for preparing thereof
CN102551056A (en) O/W (Water in Oil) type microemulsion model of fat-soluble nutrient with carbon chain length of (15 and preparation method thereof
CA1209922A (en) Emulsion-type composition for external use
CN108159414B (en) Water-in-oil adjuvant for animal vaccine and preparation method and application thereof
Cholakova et al. Self-emulsification in chemical and pharmaceutical technologies
EP0623287B1 (en) Edible microemulsions of oil, water, alcohols and surfactant
CN113876943A (en) Concentrated oil-in-water type submicron emulsion adjuvant and preparation method thereof
JP5495656B2 (en) Emulsified cosmetic for skin
CN104027262B (en) Symwhite-337 nano structured lipid carrier and preparation method thereof
CN115227589B (en) Stabilized resveratrol inclusion and preparation method thereof
CN110623846A (en) Method for preparing oil-in-water lecithin nanoemulsion and nanoemulsion obtained by same
EP1257351B1 (en) Novel family of compositions based on alkylpolyglycosides and dimerdiol, in particular for use in preparing sprayable oil-in-water emulsions
KR20160044734A (en) Cosmetic composition comprising niosome containing troxerutin
Murakami et al. Effects of sugars on the D phase emulsification of triglyceride using polyoxyethylene sorbitan fatty acid ester
KR101664877B1 (en) Cosmetic composition comprising niosome containing nitro fatty acid
CN107308019A (en) A kind of improved emulsifying agent and preparation method thereof
CN104706689A (en) Oleum fructus bruceae fat emulsion concentrated solution, preparation method and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination