CN108379223A - A kind of trimethoprim micellar preparation and preparation method thereof, trimethoprim/sulfanilamide salt compound preparation - Google Patents
A kind of trimethoprim micellar preparation and preparation method thereof, trimethoprim/sulfanilamide salt compound preparation Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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Abstract
The present invention relates to a kind of trimethoprim micellar preparation and preparation method thereof, trimethoprim/sulfanilamide salt compound preparation.The trimethoprim micellar preparation includes trimethoprim and carrier, and the carrier is polyoxyethylene poly-oxygen propylene aether block copolymer.Trimethoprim micellar preparation provided by the invention, uses polyoxyethylene poly-oxygen propylene aether block copolymer（Pluronics）Micellar preparation is made for carrier; trimethoprim shows good steady dissolution after entering the carrier micelle inner core; the grain size of micella particle greatly reduces and the protection with hydrophily shell; it is set to be substantially reduced by the risk that reticuloendothelial system is identified and removed, the residence time which adds drugs in body；Meanwhile the stripping property of the drug in micelle inner core is good, carrier can increase cutaneous permeability, thus can preferably promote drug absorption, improve bioavilability.
Description
Technical field
The invention belongs to field of veterinary medicine preparation, and in particular to a kind of trimethoprim micellar preparation and preparation method thereof, methoxy
Benzyl pyridine/sulfanilamide salt compound preparation.
Background technology
It is to inhibit dihydro leaf that trimethoprim has antibacterial action, the mechanism of action to a variety of gram-positive bacterias and negative bacterium
Sour reductase prevents it from being reduced into tetrahydrofolic acid, thus hinders sensitive bacteria folic acid metabolism and utilization, to interfere thalline nucleic acid
Synthesis.Sulfa drugs has the function of inhibiting dihydrofolate synthetase.Trimethoprim and sulfa drugs share, and can make bacterium
Folic acid metabolism by double blocking, so that antibacterial action is enhanced several times to nearly a hundred times, or even bacteriostasis is made to become bactericidal effect,
And the generation of antibody-resistant bacterium can be reduced.Trimethoprim is shared with sulfa drugs to the drug resistant Escherichia coli of sulfanilamide (SN), deformed rod
Bacterium, streptococcus pyogenes etc. also have effect.
In field of veterinary, trimethoprim and sulfa drugs such as sulfaclozine sodium, Prinzone (Squibb) etc. share can
Treat septicemia, white diarrhea, avian typhoid, cholera, respiratory system Secondary bacterial infections and ball caused by poultry Escherichia coli
Parasitosis etc..The morbidity and mortality of these diseases are very high, and it is improper such as to prevent, and huge economic loss can be caused to aquaculture.
Since pyridinyl methoxy is almost insoluble in water, absorption and the curative effect of drug are leveraged, drug is both caused
Waste, has also seriously affected the control effect to disease.Application publication number is that the patent application of CN103340868A discloses one
The preparation method of kind water soluble trimethoprim, is that trimethoprim is prepared into Trimethoprim lactate, although substantially increasing molten
Xie Xing, but trimethoprim is not used alone generally, and show alkalinity sulfa drugs share after, the analysis of sulfa drugs can be caused
Go out.The patent application that publication No. is CN103494828A discloses a kind of sulfanilamide salt, the preparation method of trimethoprim soluble powder,
It is then to mix Trimethoprim lactate coating dispersant inclusion, solubility prepared by such method with sulfanilamide salt
Powder is dispersed in water, and can only ensure not precipitate for 2 hours, but livestock and fowl drinking water administration time generally requires 6 hours or so, this kind solvable
The stabilization time of property powder is limited, can cause drug precipitation in practical applications and affect the treatment.
The patent application that publication No. is CN106265527A discloses a kind of water soluble trimethoprim composition and its compounding
Composition can be such that 0.016g trimethoprim is dissolved in 100ml water by Ultramicro-powder and hydrotropy technology, but raiser drinks water
When administration, general using concentration drinking water administration mode, concentration is much larger than this concentration, the use that cannot meet raiser is caused to be wanted
It asks.From the point of view of the applicable cases of current trimethoprim, the fitness for use of dissolubility and sulfa drugs, drug concentration, stabilization time
Etc. factors the absorption of trimethoprim and curative effect can be impacted.
It is that trimethoprim is promoted to absorb and improve one of the effective means of curative effect using inclusion technique.As publication No. is
The patent application of CN107233342A discloses a kind of solid dispersions and preparation method thereof containing trimethoprim, using water-soluble
Property carrier, Fibrinolytically active polypeptide, high molecular material, plant extract material, solid phase dispersion auxiliary material, DEXTROSE ANHYDROUS etc.
Solid dispersions are made in raw material, and water-soluble effect is good under alkaline environment, can be administered by water way with sulfanilamide salt compound.It announces
Number a kind of sulfobutyl ether-beta-cyclodextrin inclusion compound of trimethoprim is disclosed for the patent of CN105169407A, uses sulphur fourth
Base ether-beta-cyclodextrin carries out inclusion to trimethoprim as carrier and at salt, improves water-soluble and drugloading rate.
In general, although existing inclusion technique can realize good water-soluble and drugloading rate, in the form of inclusion compound
When for medicine, it is easy by reticuloendothelial system（RES）Identification and removing, the residence time in body is short, and the dissolution of drug is slow
Slowly, it is relatively low for the bioavilability of medicine form which results in this kinds, and the actual absorption of drug is still undesirable.
Invention content
The purpose of the present invention is to provide a kind of trimethoprim micellar preparations, exist to solve existing Trimpex
The low problem of bioavilability.
Second object of the present invention is to provide the preparation method of above-mentioned trimethoprim micellar preparation.
Third object of the present invention is to provide a kind of trimethoprim/sulfanilamide salt compound preparation.
To achieve the above object, the technical solution adopted in the present invention is：
A kind of trimethoprim micellar preparation, including trimethoprim and carrier, the carrier are polyoxyethylene poly-oxygen propylene aether block
Copolymer.
Trimethoprim micellar preparation provided by the invention, uses polyoxyethylene poly-oxygen propylene aether block copolymer
（Pluronics）Micellar preparation is made for carrier, trimethoprim shows good dissolving surely after entering the carrier micelle inner core
Qualitative, the grain size of micella particle greatly reduces and the protection with hydrophily shell, makes it by reticuloendothelial system（RES）Identification
It is substantially reduced with the risk of removing, the residence time which adds drugs in body；Meanwhile the drug in micelle inner core
Stripping property it is good, carrier can increase cutaneous permeability, thus can preferably promote drug absorption, improve bioavilability.
Using Pluronics as carrier, can be formed under certain Pressure, Concentration, Temperature various from coherent structure, kernel
Based on hydrophobic PPO leading portions, most of PEO blocks are looped around outer composition shell.Preferably, the carrier is by Pluronic F68
It is formed with Pluronic P123.It is further preferred that the mass ratio of Pluronic F68 and Pluronic P123 are 1：（2-
5）.A large amount of screening tests through inventor show to be used alone Pluronic F68 as carrier, and drugloading rate is relatively low,
The solution state retention time cannot reach optimum state；Pluronic P123 are used alone as carrier, because it is with higher
Hydrophobic block ratio, drugloading rate obviously increase, but the requirement of formulation process is high, working hour is longer, and cost and amplification production are difficult
Degree increases.Using Pluronic F68 and Pluronic P123 mixture as carrier, drugloading rate obviously increases, product
Grain size is smaller and is evenly distributed, while to preparation process, duration without significant change, the stability of micelle state can also be shown
It writes and improves.
The mass ratio of trimethoprim and carrier is (1-10):(20-70).The mass ratio of trimethoprim and carrier is controlled upper
State range, you can the requirement for taking into account drugloading rate and encapsulation rate makes the dissolution of drug and for concentration meet demand.Carrier amount is very few
Or it is excessive, harmful effect can be caused to drugloading rate or encapsulation rate, to influence to dissolve out and for concentration.Under these conditions, first
The drugloading rate of oxygen benzyl pyridine micellar preparation is 5%-18%, and encapsulation rate can reach 85%-98%.
The trimethoprim micellar preparation of the present invention can be added further on the basis of trimethoprim and carrier determine
Pharmaceutically acceptable adjuvant is to be made various dosage forms.Preferably, the trimethoprim micellar preparation be micellar solution or
Freeze-dried powder.Correspondingly, the freeze-dried powder further includes frozen-dried supporting agent and freeze drying protectant.The frozen-dried supporting agent and trimethoprim
Mass ratio be（0.1-5）:（0.1-1）, the mass ratio of the freeze drying protectant and trimethoprim is（0.2-0.8）:（0.05-
1）It is further preferred that the frozen-dried supporting agent is one or more combinations in mannitol, sucrose, lactose, maltodextrin.
The freeze drying protectant is PVP or lauryl sodium sulfate.PVP K30 may be selected in PVP.
Trimethoprim micellar preparation is prepared into freeze-dried powder form, stores and simple using process, there is stronger reality
With property and the scope of application.
Medicament nano micellar preparation technology is so that drug is entered by modes such as physically trapping, chemical bonding and electrostatic interactions
The kernel of micella can be prepared by film hydration method, dialysis, solvent evaporation method, and the present invention provides a kind of film water
The preparation method of change method.
The preparation method of above-mentioned trimethoprim micellar preparation, includes the following steps：
1）Trimethoprim and carrier are dissolved in organic solvent, pharmaceutical film is prepared through rotary evaporation；
2）Water is added into pharmaceutical film and carries out aquation to get trimethoprim micellar solution.
Step 1）In, the organic solvent is tetrahydrofuran, acetonitrile or chloroform.The temperature of the rotary evaporation is
35-42 DEG C, time 1-3h.After organic solvent is evaporated by rotary evaporation, can further it be dried under reduced pressure to fill organic solvent
Divide removal.
Step 2）In, the aquation is to stir 2-6h at 65-75 DEG C.It after aquation, lets cool to room temperature, reuses 0.45 μm
Filtering with microporous membrane to get the trimethoprim micellar solution.
Step 2）In, frozen-dried supporting agent and freeze drying protectant are added into trimethoprim micellar solution, freeze-dried, system
Obtain trimethoprim micelle freeze-drying powder.
The grain size of the trimethoprim micellar solution or freeze-dried powder that are prepared through the above method is mostly within 100nm.
The preparation method of trimethoprim micellar preparation provided by the invention, preparation method is simple, is highly suitable for work
Industry metaplasia is produced, and through industry's enlarging production, experiments have shown that, the grain size of products obtained therefrom is small, stability is high, can after being shared with sulfanilamide salt
Meet that dissolubility, stabilization time, drugloading rate, residence time, Fast Stripping etc. are a variety of for medicine requirement in body, substantially increases life
The targeting of object availability and drug, reduces drug dose and side effect.
Technical solution is used by trimethoprim/sulfanilamide salt compound preparation of the present invention：
A kind of trimethoprim/sulfanilamide salt compound preparation, including trimethoprim micellar preparation and sulfanilamide salt.
The sulfanilamide salt is sulfaclozine sodium or Prinzone (Squibb).
Trimethoprim provided by the invention/sulfanilamide salt compound preparation, can be prepared into soluble powder, pass through drinking water administration mode
Treat infection of livestock and poultry caused by sensitive bacteria.
Description of the drawings
Attached drawing 1：The transmission electron microscope picture of trimethoprim nano-micelle preparations particle.
Attached drawing 2：The grain size distribution of trimethoprim nano-micelle preparations particle.
Attached drawing 3：The accumulation of trimethoprim nano-micelle preparations, Ultramicro-powder trimethoprim, trimethoprim dissolves out spirogram.
Specific implementation mode
Embodiments of the present invention are described further with reference to specific embodiment.
Embodiment 1
The mass ratio of the trimethoprim micellar preparation of the present embodiment, including trimethoprim and carrier, trimethoprim and carrier is 1:
6, carrier is made of Pluronic F68, Pluronic P123, Pluronic F68, Pluronic P123 mass ratio be 1:
2。
The preparation method of the trimethoprim micellar preparation of the present embodiment, includes the following steps：
1）It is added to 5g trimethoprim, 10gPluronic F68 and 20g Pluronic P123 in round-bottomed bottle, 50ml is added
Acetonitrile is dispersed with stirring, it is made fully to dissolve, and rotary evaporation 1.5h, acetonitrile is evaporated at 42 DEG C, is then dried under reduced pressure for 80 DEG C
Night obtains transparent containing medicine film；
2）To containing 60ml deionized waters is added in medicine film, 3h is stirred under conditions of 65 DEG C, 1000r/min, is let cool to room temperature,
Using 0.45 μm of filtering with microporous membrane, transparent trimethoprim micellar solution is obtained；
3）2g mannitol and 1g PVP K30 is added to trimethoprim micellar solution, then obtained by freeze drying trimethoprim glue
Beam freeze-dried powder.
The trimethoprim of the present embodiment/sulfanilamide salt compound preparation, including trimethoprim micelle freeze-drying powder and sulfachlorpyridazine
Sodium, the mass ratio of trimethoprim and Prinzone (Squibb) is in trimethoprim micelle freeze-drying powder（1-3）：（4-15）.
The trimethoprim of the present embodiment/sulfanilamide salt compound preparation is prepared using following methods：By trimethoprim micellar preparation
It is mixed with equal increments method with sulfa drugs.
Embodiment 2
The mass ratio of the trimethoprim micellar preparation of the present embodiment, including trimethoprim and carrier, trimethoprim and carrier is 1:
6, carrier is Pluronic F68.
The preparation method of the trimethoprim micellar preparation of the present embodiment, includes the following steps：
1）6g trimethoprim, 30gPluronic F68 are added in round-bottomed bottle, 50ml acetonitriles are added, is dispersed with stirring, it is made to fill
Point dissolving, rotary evaporation 1.5h, acetonitrile is evaporated at 42 DEG C, is then dried under reduced pressure overnight for 80 DEG C, obtains transparent containing medicine film；
2）To containing 60ml deionized waters are added in medicine film, 3h is stirred under conditions of 65 DEG C, 1000r/min, lets cool to room temperature, makes
With 0.45 μm of filtering with microporous membrane, transparent trimethoprim micellar solution is obtained；
3）7g mannitol and 4g PVP K30 is added to trimethoprim micellar solution, then obtained by freeze drying trimethoprim glue
Beam freeze-dried powder.
The trimethoprim of the present embodiment/sulfanilamide salt compound preparation, including trimethoprim micelle freeze-drying powder and sulfachlorpyridazine
Sodium, the mass ratio of trimethoprim and Prinzone (Squibb) is in trimethoprim micelle freeze-drying powder（1-3）：（4-15）, specific to prepare
Method can refer to embodiment 1.
Embodiment 3
The mass ratio of the trimethoprim micellar preparation of the present embodiment, including trimethoprim and carrier, trimethoprim and carrier is 1:
5, carrier is made of Pluronic F68, Pluronic P123, Pluronic F68, Pluronic P123 mass ratio be 1:
3。
The preparation method of the trimethoprim micellar preparation of the present embodiment, includes the following steps：
1）It is added to 6g trimethoprim, 7.5gPluronic F68 and 22.5g Pluronic P123 in round-bottomed bottle, is added
90ml chloroforms, are dispersed with stirring, it is made fully to dissolve, and rotary evaporation 1.5h, chloroform is evaporated at 37 DEG C, and then 80
It DEG C is dried under reduced pressure overnight, obtains transparent containing medicine film；
2）To containing 70ml deionized waters is added in medicine film, 2.5h is stirred under conditions of 70 DEG C, 1000r/min, is let cool to room temperature,
Using 0.45 μm of filtering with microporous membrane, transparent trimethoprim micellar solution is obtained；
3）3g lactose and 1.5g PVP K30 is added to trimethoprim micellar solution, then obtained by freeze drying trimethoprim glue
Beam freeze-dried powder.
The trimethoprim of the present embodiment/sulfanilamide salt compound preparation, including trimethoprim micelle freeze-drying powder and sulfachlorpyridazine
Sodium, the mass ratio of trimethoprim and Prinzone (Squibb) is in trimethoprim micelle freeze-drying powder（1-3）：（4-15）, specific to prepare
Method can refer to embodiment 1.
Embodiment 4
The mass ratio of the trimethoprim micellar preparation of the present embodiment, including trimethoprim and carrier, trimethoprim and carrier is 8:
35, carrier is made of Pluronic F68, Pluronic P123, Pluronic F68, Pluronic P123 mass ratio be
1:4。
The preparation method of the trimethoprim micellar preparation of the present embodiment, includes the following steps：
1）It is added to 8g trimethoprim, 7gPluronic F68 and 28g Pluronic P123 in round-bottomed bottle, 60ml is added
Tetrahydrofuran is dispersed with stirring, it is made fully to dissolve, and rotary evaporation 1.5h, tetrahydrofuran is evaporated at 40 DEG C, is then subtracted for 80 DEG C
Pressure is dried overnight, and obtains transparent containing medicine film；
2）To containing 50ml deionized waters are added in medicine film, 4h is stirred under conditions of 68 DEG C, 1000r/min, lets cool to room temperature, makes
With 0.45 μm of filtering with microporous membrane, transparent trimethoprim micellar solution is obtained；
3）5g sucrose and 1.2g PVP K30 is added to trimethoprim micellar solution, then obtained by freeze drying trimethoprim glue
Beam freeze-dried powder.
The trimethoprim of the present embodiment/sulfanilamide salt compound preparation, including trimethoprim micelle freeze-drying powder and sulfachlorpyridazine
Sodium, the mass ratio of trimethoprim and Prinzone (Squibb) is in trimethoprim micelle freeze-drying powder（1-3）：（4-15）, specific to prepare
Method can refer to embodiment 1.
Embodiment 5
The mass ratio of the trimethoprim micellar preparation of the present embodiment, including trimethoprim and carrier, trimethoprim and carrier is 1:
3, carrier is made of Pluronic F68, Pluronic P123, Pluronic F68, Pluronic P123 mass ratio be 1:
5。
The preparation method of the trimethoprim micellar preparation of the present embodiment, includes the following steps：
1）It is added to 12g trimethoprim, 6gPluronic F68 and 30g Pluronic P123 in round-bottomed bottle, 70ml is added
Chloroform is dispersed with stirring, it is made fully to dissolve, and rotary evaporation 1.5h, chloroform is evaporated at 35 DEG C, is then subtracted for 80 DEG C
Pressure is dried overnight, and obtains transparent containing medicine film；
2）To containing 60ml deionized waters are added in medicine film, 3h is stirred under conditions of 68 DEG C, 1000r/min, lets cool to room temperature, makes
With 0.45 μm of filtering with microporous membrane, transparent trimethoprim micellar solution is obtained；
3）7g mannitol and 1.4g lauryl sodium sulfate is added to trimethoprim micellar solution, then obtained by freeze drying
Trimethoprim micelle freeze-drying powder.
The trimethoprim of the present embodiment/sulfanilamide salt compound preparation, including trimethoprim micelle freeze-drying powder and sulfachlorpyridazine
Sodium, the mass ratio of trimethoprim and Prinzone (Squibb) is in trimethoprim micelle freeze-drying powder（1-3）：（4-15）, specific to prepare
Method can refer to embodiment 1.
In the other embodiment of the trimethoprim micellar preparation of the present invention, the usage ratio of trimethoprim and carrier can be according to
According to needing to be adaptively adjusted in the framework of the present definition, organic solvent, frozen-dried supporting agent, freeze drying protectant etc. are medicinal
The selection of adjuvant is not limited to the specific substance in above example, does not generate side effect with bulk pharmaceutical chemicals, can play corresponding work(
Energy.
Test example 1
This test example detects drugloading rate, dissolubility and the dissolubility retention time of the trimethoprim micelle freeze-drying powder of each embodiment,
Drugloading rate is detected with liquid chromatography；Deliquescent detection is that 3g trimethoprim micelle freeze-drying powder is added in 100ml water,
Observe solution state；The evaluation criterion of dissolubility retention time is that precipitation is not precipitated, and concrete outcome is as shown in table 1.
The drugloading rate and dissolving implementations of the trimethoprim micelle freeze-drying powder of 1 each embodiment of table
（Remarks：Drugloading rate refers to the content of trimethoprim in micelle freeze-drying powder.）
As shown in Table 1, the drugloading rate of trimethoprim micellar preparation of the invention can reach 5.2%-16%, disclosure satisfy that methoxy benzyl
Pyridine for concentration demand, the favorable solubility of compound preparation is adopted compared with the embodiment 2 of single use Pluronic F68
Use Pluronic F68 and Pluronic P123 mixing as complex carrier, when can effectively improve drugloading rate and dissolubility holding
Between.
Test example 2
The transmission electron microscope picture and its particle diameter distribution of the trimethoprim micellar preparation of this test example detection embodiment 3 and the micella
The dissolving out capability of preparation and Ultramicro-powder trimethoprim, trimethoprim.
After the trimethoprim micelle freeze-drying powder of preparation is added suitable quantity of water to redissolve by Fig. 1, drop is used on electron microscopyc sample preparation copper mesh
After the dyeing of 2.5% phosphotungstic acid, through transmission electron microscope observation, and take pictures.See Fig. 1
Fig. 2 is to dilute the appropriate tri-distilled water of trimethoprim nano-micelle preparations obtained, its grain size is measured with Particle Size Analyzer
Size and distribution.Known by Fig. 2, the grain size of trimethoprim nano-micelle preparations is mostly within 100nm.
Fig. 3 take trimethoprim, Ultramicro-powder trimethoprim, the present invention trimethoprim micellar preparation, each 6 parts, according to slurry processes
It measures, dissolution medium is pH6.8 phosphate buffer 900ml, and rotating speed 100r/min, water temperature is 37 ± 0.5 DEG C, is being advised respectively
It fixes time and interior sampling and is filtered through 0.22 μm of miillpore filter, while supplementing equivalent fresh medium, sample calculates after assay
The accumulation dissolution rate of different time.
As seen from Figure 3, the trimethoprim accumulation stripping quantity of the trimethoprim micellar preparation of embodiment 3 is much better than ultra micro
Powder trimethoprim, trimethoprim, be on the one hand due to the grain size of micellar preparation is small and with hydrophily shell protection, it is netted
Endothelial system（RES）Identification and the risk removed substantially reduce, and are on the other hand to increase the molten of TMP since micellar preparation is made
Solution property and carrier have rush release action to TMP, to improve the targeting of bioavilability and drug, reduce drug dosage and
Side effect.
Claims (10)
1. a kind of trimethoprim micellar preparation, which is characterized in that including trimethoprim and carrier, the carrier is poly- for polyoxyethylene
Oxypropylene ether block copolymers.
2. trimethoprim micellar preparation as described in claim 1, which is characterized in that the mass ratio of trimethoprim and carrier is
(1-10):(20-70)。
3. trimethoprim micellar preparation as claimed in claim 2, which is characterized in that the carrier by Pluronic F68 and
Pluronic P123 compositions.
4. trimethoprim micellar preparation as claimed in claim 3, which is characterized in that Pluronic F68 and Pluronic
The mass ratio of P123 is 1：（2-5）.
5. trimethoprim micellar preparation as described in claim 1, which is characterized in that the trimethoprim micellar preparation is micella
Solution or freeze-dried powder.
6. trimethoprim micellar preparation as claimed in claim 5, which is characterized in that the freeze-dried powder further includes frozen-dried supporting agent
And freeze drying protectant.
7. a kind of preparation method of trimethoprim micellar preparation as described in claim 1, which is characterized in that including following step
Suddenly：
1）Trimethoprim and carrier are dissolved in organic solvent, pharmaceutical film is prepared through rotary evaporation；
2）Water is added into pharmaceutical film and carries out aquation to get trimethoprim micellar solution.
8. preparation method as claimed in claim 7, which is characterized in that step 2）In, the aquation is stirred at 65-75 DEG C
2-6h。
9. preparation method as claimed in claim 7, which is characterized in that step 2）In, it is added into trimethoprim micellar solution
Frozen-dried supporting agent and freeze drying protectant, it is freeze-dried, trimethoprim micelle freeze-drying powder is made.
10. a kind of trimethoprim/sulfanilamide salt compound preparation, which is characterized in that including trimethoprim micella described in claim 1
Preparation and sulfanilamide salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810137057.4A CN108379223A (en) | 2018-02-10 | 2018-02-10 | A kind of trimethoprim micellar preparation and preparation method thereof, trimethoprim/sulfanilamide salt compound preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810137057.4A CN108379223A (en) | 2018-02-10 | 2018-02-10 | A kind of trimethoprim micellar preparation and preparation method thereof, trimethoprim/sulfanilamide salt compound preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108379223A true CN108379223A (en) | 2018-08-10 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112336725A (en) * | 2020-12-11 | 2021-02-09 | 吴照球 | Novel medical application of trimethoprim |
| CN116570556A (en) * | 2023-05-17 | 2023-08-11 | 郑州福源动物药业有限公司 | Compound sulfachlordazine sodium solution for treating escherichia coli and pasteurellosis infection of livestock and poultry and preparation method thereof |
-
2018
- 2018-02-10 CN CN201810137057.4A patent/CN108379223A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| LIYAN ZHAO等: "Curcumin loaded mixed micelles composed of Pluronic P123 and F68: Preparation, optimization and in vitro characterization", 《COLLOIDS AND SURFACES B: BIOINTERFACES》 * |
| SINEM GOKTURK等: "A Study on Solubilization of Poorly Soluble Drugs by Cyclodextrins andMicelles: Complexation and Binding Characteristics of Sulfamethoxazole and Trimethoprim", 《THE SCIENTIFICWORLD JOURNAL》 * |
| 王开贞，徐红编著: "《药物应用护理》", 30 June 2009, 山东大学出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112336725A (en) * | 2020-12-11 | 2021-02-09 | 吴照球 | Novel medical application of trimethoprim |
| CN116570556A (en) * | 2023-05-17 | 2023-08-11 | 郑州福源动物药业有限公司 | Compound sulfachlordazine sodium solution for treating escherichia coli and pasteurellosis infection of livestock and poultry and preparation method thereof |
| CN116570556B (en) * | 2023-05-17 | 2023-11-07 | 郑州福源动物药业有限公司 | Compound sulfachlordazine sodium solution for treating escherichia coli and pasteurellosis infection of livestock and poultry and preparation method thereof |
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