CN110200913A - A kind of preparation method embedding Sulbactam amoxicillin amide compound - Google Patents
A kind of preparation method embedding Sulbactam amoxicillin amide compound Download PDFInfo
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Abstract
The invention discloses a kind of preparation methods for embedding Sulbactam amoxicillin amide compound, and albumen composition in pale blue and glucan covalent reaction are obtained graft, i.e. water phase in water first；Sulbactam amoxicillin amide compound is dissolved again and obtains oily phase in soybean oil；Then pass through the nanoemulsions of the high-pressure homogeneous Sulbactam amoxicillin amide compound drug that water phase and oil are mixed to obtained embedding.The nanoemulsions have stable oil-water interfacial film, and good water solubility brings possibility for the preparation production of above-mentioned compound；It is good to embed effect, soilless sticking or clustering phenomena within December, particle stable homogeneous, and partial size is smaller, can preferably be absorbed by the body.Raw material is simple and easy to get, and safety, at low cost, preparation process is simple, is easy to apply in industrialized production, provides new approaches for the production of Fat soluble drug preparation, while can also promote the comprehensive development and utilization of egg product industry high added value ingredient, improves economic value.
Description
Technical field
The present invention relates to pharmaceutical technology fields, in particular to a kind of system for embedding Sulbactam amoxicillin amide compound
Preparation Method.
Background technique
Sulbactam is artificial synthesized irreversible competitive beta-lactamase inhibitor, and the antibacterial activity of itself is weak, slightly
It is better than clavulanic acid, only has bactericidal effect to gonococcus and acinetobacter when being applied alone, it is to gram-positive bacteria and gram
Most beta-lactamases of negative bacterium production have powerful inhibiting effect.Amoxicillin has a broad antifungal spectrum, sterilizing power are strong, act on
Rapidly, clinic is widely used in because of its Orally-administrable；It can be used for treating typhoid fever, other Salmonella infections, typhoid carrier, urinate
The infection in road, ear, nose, larynx, respiratory tract and soft tissue.WHO is recommended as preferred beta-lactam oral antibiotic, it has also become
One of kind most noticeable, with fastest developing speed in antibiotic kind.But since beta-lactam structure is easy in the molecule of Amoxicillin
Open-loop unstable is easily degraded, and poorly water-soluble, is mostly used its sodium salt in injection.There is also certain unstable for Sulbactam
Property problem, is influenced by factors such as pH, temperature, oxidations, and beta-lactam structure also Yi Kaihuan causes entire molecule to be destroyed, contains
Amount decline, related object increase.
It is a kind of relatively common method at salt, at the modification of ester and amide in the modifying for chemical structure of organic drug.
Using two kinds of different pharmaceutical molecules with collaboration sexual function, after the modification of these methods, by the structure of two kinds of drugs
Split is compatible in a molecule in an intramolecular, or by the pharmacophoric group of the two, is current drug worker research interest
One of.The present inventor (CN201210290947.1) in early-stage study, using modification technique by Amoxicillin and Sulbactam ester
Sulbactam amoxicillin amide compound is formed by amidation, realizes a kind of new structural Sulbactam amoxicillin amide
The synthesis of compound, structural formula are as follows:
Drug after transformation modification on the amide composite structure
To a certain extent, pharmacological action can be strengthened, reduce respective toxic side effect；Or the two is made to learn from other's strong points to offset one's weaknesses, it plays each
From pharmacological activity, synergistically complete therapeutic process；And it is more convenient for expanding the treatment and control of clinical use and disease after modifying.
But the water-soluble of Sulbactam amoxicillin amide compound is lower, brings many inconvenience to preparation production, limits its system
The development of agent type especially aqueous solution preparation, while the amide compound still belongs to beta-lactam structure, how to improve in preparation
Its stability and major issue urgently to be solved.
Summary of the invention
In view of the above shortcomings of the prior art, the object of the present invention is to provide a kind of embedding Sulbactam Amoxicillin acyls
The preparation method of amine compound solves the poorly water-soluble of Sulbactam amoxicillin amide compound, it is difficult to the water-soluble system of preparation
The problem of beta-lactam structural stability difference in agent and the composite structure.
In order to solve the above-mentioned technical problem, present invention employs the following technical solutions: a kind of embedding Sulbactam Ah Moses
The preparation method of woods amide compound, comprising the following steps:
1) pale blue is soluble in water, glucan is then added and obtains mixed solution, then by the pH tune of the mixed solution
To 4~8,1~2h is stirred at room temperature to being completely dissolved, and place it in 1~6h of reaction in 50 DEG C of water-baths, is cooled to after reaction
Room temperature, centrifuging and taking supernatant, then graft, i.e. water phase are obtained through dialysis；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, obtain oily phase；
3) water phase that step 1) obtains and the oil that step 2) obtains are mixed, obtains embedding Sulbactam by high-pressure homogeneous
The nanoemulsions of amoxicillin amide compound.
The transparent glue of pale blue, mainly comprising protein, fat, carbohydrate, calcium, phosphorus, iron, riboflavin, niacin,
The ingredients such as vitamin A and C.Wherein, solid content proportion 13%, about 90% is protein in solid content, and with albumen egg
Bai Weizhu (75%), ovalbumin exist mostly in the form of hydrophilic protein, and most hydrophobic acidic amino acid is in intramolecule,
Easily it is unfolded in the groups such as high-pressure homogeneous and calcium, phosphorus, iron effect flowering structure, with ovomucoid (15%), ovomucin (7%)
The albumen composition to interact between conalbumin (3%), thus assign its intermolecular stronger hydrophobic interaction and
Disulfide bond crosslinking has the ability for being quickly adsorbed onto interface, can stretch and be orientated and reach boundary rapidly after reaching interface
Behind face, i.e., interact the film to be formed with strong cohesive force and viscoelasticity with neighboring molecule, forms the protein of particular category
Class surfactant；And in above-mentioned albumen composition and egg white under the synergistic effect of ovotransferrins and lysozyme, further
Improve its emulsifying effectiveness.The ingredient of pale blue is in protein types, microelement and other nutrients etc. and other egg white
It has differences, the difference on these ingredients may cause pale blue suitable for embedding Sulbactam amoxicillin amide compound medicine
Object.
Generated intensive shear, shock and cavitation under high pressure, egg white, which is formed, has protein-based surface-active
The albumen composition of agent, the hydrophilic radical and water of the albumen composition combine, and lipophilic group and oil combine, egg compound in this way
The white emulsion droplet surface that can be strapped in forms oil-water interfacial film, to obtain, oil droplet is fixed and to complete Sulbactam amoxicillin amide compound
The high-efficient carrier of object drug and embedding form and numerous small have been even up to micron or nanoscale lotion.Pass through utilization
The microjet that cavitation effect generates is mixed evenly oily phase and water phase, liquid is made to obtain Ultrafine.It is grafted connection simultaneously
Glucan on albumen is due to its hydrophily and in emulsion droplet surface extension, and making emulsion droplet, long-time stable exists in water,
It is avoided to precipitate and assemble.
Preferably, the quality of the pale blue, water and glucan is 1:2~10:0.05~0.2.
Preferably, the molecular weight of the glucan is 5000~50000.
Preferably, it is 5 that step 2) the Sulbactam amoxicillin amide compound, which is dissolved in the concentration in soybean oil,
~100mg/ml.
Preferably, the mixed volume ratio of the water phase and oily phase is 1:5~20.
Preferably, the high-pressure homogeneous pressure limit be 300~500bar, high-pressure homogeneous time range be 10~
30min。
Preferably, the centrifugal speed is 4000~6000rpm, centrifugation time is 10~20min.
Preferably, the molecular weight of dialysis membrane is 10 ± 0.2kDa in the dialysis.
Compared with prior art, the invention has the following beneficial effects:
1, Sulbactam amoxicillin amide compound drug-protein complex-glucan embedding type provided by the present invention
Nanoemulsions are a kind of with oily mutually for kernel comprising Sulbactam amoxicillin amide compound drug, and albumen is compound in pale blue
Object is oil-water interfacial film, and the glucan being grafted on albumen composition is in nanoemulsions outer layer.The nanoemulsions have stable
Oil-water interfacial film avoids emulsion droplet from assembling due to dextran hydrophilic in emulsion droplet surface extension, good water solubility, is above-mentioned multiple
The preparation production for closing object brings possibility；It is good to embed effect, improves the stability of compound, soilless sticking or aggregation within December
Phenomenon improves the effective storage life of Sulbactam amoxicillin amide compound drug, has a good application prospect.
2, nanoemulsions particle stable homogeneous prepared by the present invention, and partial size is smaller, can preferably be absorbed by the body.Make
It is multiple that used time releases Sulbactam amoxicillin amide under the action of human digestive enzymes with the degradation of glucan and protein
Object drug is closed, corresponding effect is played；Obtained glucose is decomposed simultaneously and protein peptides also provide nutriment for human body.
3, the present invention belongs to general food using glucan and pale blue as raw material, nontoxic degradable, safety, at low cost, preparation
Simple process, it is with short production cycle, it is easy to apply in industrialized production, also the production for Fat soluble drug preparation provides newly
Thinking, while can also promote the comprehensive development and utilization of egg product industry high added value ingredient, improve economic value.
Detailed description of the invention
Fig. 1 is Sulbactam amoxicillin amide compound drug-protein complex-after the preparation embedding of the embodiment of the present invention 1
The nano particle diameter distribution map of glucan nanoemulsions.
Specific embodiment
Below with reference to embodiment, the present invention is described in further detail.
Embodiment 1
1) pale blue is dissolved in the distilled water of 2 times of volumes in reaction flask, it is poly- that the Portugal that molecular weight is 25000 is then added
Sugar makes 0.05 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution with phosphate buffer solution and arrive
4.0,2h is stirred at room temperature to being completely dissolved, and place it in 40 DEG C of water-baths and react 1h, is cooled to room temperature after reaction, in
4000rpm is centrifuged 15min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 5mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 5:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 500bar, and the high-pressure homogeneous time is 10min.
Embodiment 2
1) pale blue is dissolved in the distilled water of 10 times of volumes in reaction flask, the Portugal that molecular weight is 50000 is then added
Glycan makes 0.2 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution with phosphate buffer solution and arrive
8.0,2h is stirred at room temperature to being completely dissolved, and place it in 40 DEG C of water-baths and react 6h, is cooled to room temperature after reaction, in
6000rpm is centrifuged 10min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 100mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 20:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 400bar, and the high-pressure homogeneous time is 30min.
Embodiment 3
1) pale blue is dissolved in the distilled water of 5 times of volumes in reaction flask, it is poly- that the Portugal that molecular weight is 5000 is then added
Sugar, makes 0.1 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution to 5.0 with phosphate buffer solution,
2h is stirred at room temperature to being completely dissolved, and places it in 40 DEG C of water-baths and reacts 2h, is cooled to room temperature after reaction, in
5000rpm is centrifuged 20min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 50mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 10:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 300bar, and the high-pressure homogeneous time is 20min.
Embodiment 4
1) pale blue is dissolved in the distilled water of 5 times of volumes in reaction flask, it is poly- that the Portugal that molecular weight is 30000 is then added
Sugar makes 0.15 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution with phosphate buffer solution and arrive
7.0,2h is stirred at room temperature to being completely dissolved, and place it in 40 DEG C of water-baths and react 1h, is cooled to room temperature after reaction, in
4000rpm is centrifuged 20min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 20mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 10:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 400bar, and the high-pressure homogeneous time is 15min.
Embodiment 5
1) pale blue is dissolved in the distilled water of 5 times of volumes in reaction flask, it is poly- that the Portugal that molecular weight is 40000 is then added
Sugar, makes 0.2 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution to 6.0 with phosphate buffer solution,
2h is stirred at room temperature to being completely dissolved, and places it in 40 DEG C of water-baths and reacts 1h, is cooled to room temperature after reaction, in
4000rpm is centrifuged 15min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 50mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 15:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 500bar, and the high-pressure homogeneous time is 10min.
Embodiment 6
1) pale blue is dissolved in the distilled water of 10 times of volumes in reaction flask, it is poly- that the Portugal that molecular weight is 6000 is then added
Sugar makes 0.05 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution with phosphate buffer solution and arrive
4.0,2h is stirred at room temperature to being completely dissolved, and place it in 40 DEG C of water-baths and react 2.5h, is cooled to room temperature after reaction, in
6000rpm is centrifuged 10min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 50mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 10:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 300bar, and the high-pressure homogeneous time is 20min.
Embodiment 7
1) pale blue is dissolved in the distilled water of 2 times of volumes in reaction flask, it is poly- that the Portugal that molecular weight is 10000 is then added
Sugar, makes 0.2 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution to 4.0 with phosphate buffer solution,
2h is stirred at room temperature to being completely dissolved, and places it in 40 DEG C of water-baths and reacts 5h, is cooled to room temperature after reaction, in
6000rpm is centrifuged 20min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 50mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 10:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 300bar, and the high-pressure homogeneous time is 20min.
Embodiment 8
1) pale blue is dissolved in the distilled water of 5 times of volumes in reaction flask, it is poly- that the Portugal that molecular weight is 25000 is then added
Sugar, makes 0.2 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution to 5.0 with phosphate buffer solution,
2h is stirred at room temperature to being completely dissolved, and places it in 40 DEG C of water-baths and reacts 5h, is cooled to room temperature after reaction, in
4000rpm is centrifuged 20min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 50mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 5:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 300bar, and the high-pressure homogeneous time is 30min.
Embodiment 9
1) pale blue is dissolved in the distilled water of 2 times of volumes in reaction flask, it is poly- that the Portugal that molecular weight is 10000 is then added
Sugar, makes 0.2 times of the additive amount pale blue quality of glucan, then adjusts above-mentioned pH value of solution to 7.0 with phosphate buffer solution,
2h is stirred at room temperature to being completely dissolved, and places it in 40 DEG C of water-baths and reacts 5h, is cooled to room temperature after reaction, in
4000rpm is centrifuged 15min and removes insoluble matter, and taking must be grafted after dialysing (dialysis 10 ± 0.2kDa of molecular weight) for 24 hours at 4 DEG C of supernatant
Object, as water phase；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, make Sulbactam Amoxicillin acyl
The concentration of amine compound is 50mg/ml, obtains oily phase；
3) oil that water phase and step 2) that step 1) obtains obtain mutually is mixed according to volume ratio 10:1, by high-pressure homogeneous
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanoemulsions after obtaining the embedding, wherein high
The pressure for pressing homogeneous is 500bar, and the high-pressure homogeneous time is 20min.
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanometer water and milk prepared by embodiment 1
Liquid detects emulsion particle diameter by laser particle analyzer, as a result such as Fig. 1.It can be seen from the figure that Sulbactam Ah not prepared by the present invention
XiLin amide compound drug-protein complex-glucan nanometer aqueous emulsion partial size is about 237.7 ± 9.31nm, the lotion
It can achieve the purpose that degerming by 450nm filter membrane.
Sulbactam amoxicillin amide compound drug-protein complex-glucan nanometer prepared by Examples 1 to 9
Aqueous emulsion is measured its partial size and drugloading rate in different time sections, and the results are shown in Table 1.
Table 1
As can be seen from Table 1, in different time period, nanoemulsions prepared by the present invention are to Sulbactam amoxicillin amide
The drugloading rate of compound drug does not have significant change, illustrates it with good embedding effect, in 12 months soilless sticking or
Clustering phenomena illustrates that its is with good stability；Particle stable homogeneous, soilless sticking phenomenon, illustrates preparation in aqueous solution
Nanoemulsions have good water solubility, and partial size is smaller, easily absorb.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not limitation with the present invention, all in essence of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (8)
1. a kind of preparation method for embedding Sulbactam amoxicillin amide compound, which comprises the following steps:
1) pale blue is soluble in water, glucan is then added and obtains mixed solution, then the pH of the mixed solution is adjusted to 4~
8,1~2h is stirred at room temperature to being completely dissolved, and place it in 1~6h of reaction in 50 DEG C of water-baths, is cooled to room temperature after reaction,
Centrifuging and taking supernatant, then water phase is obtained through dialysis；
2) Sulbactam amoxicillin amide compound is dissolved in soybean oil and is sufficiently stirred, obtain oily phase；
3) water phase that step 1) obtains and the oil that step 2) obtains are mixed, obtains the embedding Sulbactam by high-pressure homogeneous
The nanoemulsions of amoxicillin amide compound.
2. embedding the preparation method of Sulbactam amoxicillin amide compound according to claim 1, which is characterized in that described
The quality of pale blue, water and glucan is 1:2~10:0.05~0.2.
3. embedding the preparation method of Sulbactam amoxicillin amide compound according to claim 1, which is characterized in that described
The molecular weight of glucan is 5000~50000.
4. embedding the preparation method of Sulbactam amoxicillin amide compound according to claim 1, which is characterized in that step
2) it is 5~100mg/ml that the Sulbactam amoxicillin amide compound, which is dissolved in the concentration in soybean oil,.
5. embedding the preparation method of Sulbactam amoxicillin amide compound according to claim 1, which is characterized in that described
The mixed volume ratio of water phase and oily phase is 1:5~20.
6. embedding the preparation method of Sulbactam amoxicillin amide compound according to claim 1, which is characterized in that described
High-pressure homogeneous pressure is 300~500bar, and the high-pressure homogeneous time is 10~30min.
7. embedding the preparation method of Sulbactam amoxicillin amide compound according to claim 1, which is characterized in that described
Centrifugal speed is 4000~6000rpm, and centrifugation time is 10~20min.
8. embedding the preparation method of Sulbactam amoxicillin amide compound according to claim 1, which is characterized in that described
The molecular weight of dialysis is 10 ± 0.2kDa.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08104620A (en) * | 1994-10-05 | 1996-04-23 | Green Cross Corp:The | Fat emulsion containing medicine |
| WO2006090110A1 (en) * | 2005-02-23 | 2006-08-31 | Imperial Chemical Industries Plc | Emulsifiers and emulsions |
| CN102302450A (en) * | 2011-09-06 | 2012-01-04 | 复旦大学 | Hydrophobic drug-albumin-glucan nano emulsion, as well as preparation method and application thereof |
| CN102786536A (en) * | 2012-08-16 | 2012-11-21 | 重庆大学 | Sulbactam amoxicillin amide complex for treatment of acute bacterial infection of pig and synthesis method |
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2019
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08104620A (en) * | 1994-10-05 | 1996-04-23 | Green Cross Corp:The | Fat emulsion containing medicine |
| WO2006090110A1 (en) * | 2005-02-23 | 2006-08-31 | Imperial Chemical Industries Plc | Emulsifiers and emulsions |
| CN102302450A (en) * | 2011-09-06 | 2012-01-04 | 复旦大学 | Hydrophobic drug-albumin-glucan nano emulsion, as well as preparation method and application thereof |
| CN102786536A (en) * | 2012-08-16 | 2012-11-21 | 重庆大学 | Sulbactam amoxicillin amide complex for treatment of acute bacterial infection of pig and synthesis method |
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