CN101411870A - Method for preparing chicken interferon long-acting sustained-release dosage form - Google Patents
Method for preparing chicken interferon long-acting sustained-release dosage form Download PDFInfo
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- CN101411870A CN101411870A CNA2008100534107A CN200810053410A CN101411870A CN 101411870 A CN101411870 A CN 101411870A CN A2008100534107 A CNA2008100534107 A CN A2008100534107A CN 200810053410 A CN200810053410 A CN 200810053410A CN 101411870 A CN101411870 A CN 101411870A
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Abstract
The invention discloses a method for preparing a chicken interferon long-term slow release formulation which is capable of being injected intramuscularly once each week. The method is characterized in that the chicken interferon long-term slow release formulation is prepared by the double emulsion solvent evaporation method; lactide/glycolide multipolymer is taken as microsphere carrier; a chicken interferon is taken as a coating object; and the release characteristic in vitro of the prepared chicken interferon long-term slow release formulation meets the characteristic of long-term preparation. The method has the advantages that the chicken interferon long-term slow release formulation for injection overcomes the defects that the prior chicken interferon injection needs frequent injection for a long term and has inconvenient use, low biological utilization rate and large using amount of medicine, can have antiviral effect for a longer term after once injection, and is an ideal chicken interferon long-term slow release formulation. The chicken interferon long-term slow release formulation is easy to prepare, easy and convenient to apply, and easy to be absorbed, and has better effect of treating chicken virosis.
Description
Technical field
The invention belongs to the technology of preparing of bio-pharmaceutical, particularly a kind of preparation method of chicken interferon long-acting sustained-release dosage form.
Background technology
At present, chicken interferon all is with the administration of injection, and better therapeutic effect is arranged usually, but many persons need inject 1-2 times every day, logotype 2-5 days brings a lot of inconvenience for the use of culturing the owner, and therefore being made into long-acting dosage form just becomes the target that people pursue.Defectives such as existing chicken interferon exists needs long-term frequent injection, use inconvenience, bioavailability is low and the drug use amount is big.
Therefore, providing a kind of preparation method of chicken interferon long-acting sustained-release dosage form, effectively prevent and treat various chicken viral diseases, is one of this technical field scientific research personnel new problem of being badly in need of developing.
Summary of the invention
The objective of the invention is for overcoming the weak point of prior art, provide a kind of and prepare simply, use preparation method convenient, the obvious results chicken interferon long-acting sustained-release dosage form.
A kind of preparation method of chicken interferon long-acting sustained-release dosage form is characterized in that comprising the steps:
(1) a certain amount of chicken interferon is dissolved in the PBS buffer solution that contains stabilizing agent, makes aqueous phase solution (W1), the content of chicken interferon is 0.5-50 mg/ml;
(2) hand over fat/glycolide copolymer to make oil-phase solution (O) with the dichloromethane dissolving with third, the content of third friendship fat/glycolide copolymer is 0.1-0.5 grams per milliliter; The above-mentioned aqueous phase solution (W1) that contains chicken interferon is joined in the oil-phase solution (O), oil-phase solution (O) is 20: 1 to 2: 1 with the ratio of aqueous phase solution (W1), these two kinds of solution are stirred down for 5-30 ℃ in temperature, mixing speed is 500-8000 rev/mins, mixing time is 0.02-0.2 hour, mix homogeneously; Make colostrum W1/O, preserve down at 4-10 ℃;
(3) polyvinyl alcohol fully is dissolved in water and makes aqueous phase solution (W2), the weight concentration of polyvinyl alcohol is 0.5-50%; Above-mentioned colostrum W1/O is joined aqueous phase solution (W2) stir, whipping temp is 5-30 ℃, and mixing speed is 100-3000 rev/mins, and mixing time is 0.2-0.5 hour; The ratio of colostrum W1/O and aqueous phase solution (W2) is 1: 50 to 1: 200, makes emulsion W1/O/W2, preserves down at 4-10 ℃;
(4) emulsion W1/O/W2 is transferred in the NaCl aqueous solution of 1-5%, stir, whipping temp is 5-30 ℃, and mixing speed is 500-3000 rev/mins, and mixing time is 0.2-0.5 hour, makes the organic solvent volatilization, centrifugal then collection microsphere;
(5) in order to keep the stable of solution, add certain amount of stabilizer, stabilizing agent directly joins in described preparation process (1) solution.
Described stabilizing agent is selected from one or more of trehalose, bovine serum albumin and Polyethylene Glycol.
The addition of described stabilizing agent is 0.1%-10% of a final solution.
Described chicken interferon is reorganization chicken genetic engineering interferon IFN-α, IFN-β and the natural LeIF of chicken.
The beneficial effect of the inventive method is: this injection chicken interferon long-acting sustained-release dosage form can reduce chicken interferon medication number of times, is a kind of ideal chicken interferon long-acting dosage form.It is simple to have preparation technology, realizes easily, and it is convenient to use, characteristics such as required cost is low, this method adopt toxicity little, materials such as the dispersant of injection safety and oil phase, make the uniform dispersing and dissolving of chicken interferon in oil phase, finally become a kind of long-acting dosage form of chicken interferon.Adopt the long-acting dosage form experiment in vitro of the chicken interferon that this method makes to show, disturbing element with chicken is the parcel object, prepared chicken interferon microsphere form rounding, even particle size distribution, particle size distribution is below 40 microns, and drug loading can reach more than 6.0%, and envelop rate is more than 30.0%, external slow release can reach 4 all releases, meets the durative action preparation feature.Can bring into play the antiviral drug effect in a long time after the shot.Chicken interferon is made microball preparation, can prolong drug action time, improve curative effect of medication and economic benefit greatly.
The specific embodiment
Below in conjunction with embodiment, to details are as follows according to the specific embodiment provided by the invention:
Embodiment 1
A kind of preparation method of chicken interferon long-acting sustained-release dosage form is characterized in that concrete implementation step is as follows:
(1) 40 milligrams of chicken genetic engineering interferon IFN-α is dissolved in 1 milliliter of PBS buffer solution that contains 2% trehalose, makes aqueous phase solution (W1);
(2) hand over fat/glycolide copolymer to be dissolved in 4 milliliters of dichloromethane with 1000 milligram third and make oil-phase solution (O);
(3) the above-mentioned aqueous phase solution (W1) that contains chicken interferon is joined in the oil-phase solution (O), make these two kinds of solution under 15 ℃ of temperature, mixing speed is that 8000 rev/mins, mixing time are 0.05 hour, mix, make colostrum W1/O, preserve down at 4-10 ℃;
(4) above-mentioned colostrum W1/O is joined under 1500 rev/mins of stirring states in 300 milliliter 2% the polyvinyl alcohol, whipping temp is 5-30 ℃, and mixing time is 0.2 hour, makes emulsion W1/O/W2, preserves down at 4-10 ℃;
(5) emulsion W1/O/W2 is joined in the 1%NaCl aqueous solution of 3 times of emulsion volumes, make the organic solvent volatilization by 1500 rev/mins of stirrings, 2000 rev/mins then, centrifugal 15 minutes, collect microsphere, deposit in refrigerator and cooled and hide.
Prepared chicken interferon microsphere form rounding, even particle size distribution, mean diameter are at 21.2 microns, and drug loading can reach 8.9%, and envelop rate is 35.9%, and extracorporeal releasing experiment shows that slow release can reach for 4 weeks, meets the durative action preparation feature.Zoopery proves this new forms of interferon except that the anti-fowl disease toxic action with interferon, and its half-life in vivo is 3 times of common chicken interferon, thereby has prolonged its action time in vivo.
Embodiment 2
A kind of preparation method of chicken interferon long-acting sustained-release dosage form is characterized in that concrete implementation step is as follows:
(1) 80 milligrams of natural LeIFs of chicken is dissolved in 1.5 milliliters of PBS buffer solution that contain 2% bovine serum albumin, makes aqueous phase solution (W1);
(2) hand over fat/glycolide copolymer to be dissolved in 4 milliliters of dichloromethane with 1200 milligram third and make oil-phase solution (O);
(3) the above-mentioned aqueous phase solution (W1) that contains chicken interferon is joined in the oil-phase solution (O), make these two kinds of solution under 15 ℃ of temperature, mixing speed is that 8000 rev/mins, mixing time are 0.05 hour, mix, make colostrum W1/0, preserve down at 4-10 ℃;
(4) above-mentioned colostrum W1/O is joined under 2000 rev/mins of stirring states in 400 milliliter 3% the polyvinyl alcohol, whipping temp is 5-30 ℃, and mixing time is 0.2 hour, makes emulsion W1/O/W2, preserves down at 4-10 ℃;
(5) emulsion W1/O/W2 is joined in the 1%NaCl aqueous solution of 2 times of emulsion volumes, makes organic solvent volatilization by 1000 rev/mins of stirrings, then 1300 rev/mins centrifugal 20 minutes, collect microsphere, deposit in refrigerator and cooled and hide.
Prepared chicken interferon microsphere form rounding, even particle size distribution, mean diameter are at 15.9 microns, and drug loading can reach 6.9%, and envelop rate is 31.8%, and extracorporeal releasing experiment shows that slow release can reach for 3 weeks, meets the durative action preparation feature.Zoopery proves this new forms of interferon except that the anti-fowl disease toxic action with interferon, and its half-life in vivo is 4.2 times of common chicken interferon, thereby has prolonged its action time in vivo.
Embodiment 3
A kind of preparation method of chicken interferon long-acting sustained-release dosage form is characterized in that concrete implementation step is as follows:
(1) 20 milligrams of chicken genetic engineering interferon IFN-β is dissolved in 0.5 milliliter of PBS buffer solution that contains 2% Macrogol 4000, makes aqueous phase solution (W1);
(2) hand over fat/glycolide copolymer to be dissolved in 2 milliliters of dichloromethane with 800 milligram third and make oil-phase solution (O);
(3) the above-mentioned aqueous phase solution (W1) that contains chicken interferon is joined in the oil-phase solution (O), make these two kinds of solution under 15 ℃ of temperature, mixing speed is that 8000 rev/mins, mixing time are 0.05 hour, mix, make colostrum W1/O, preserve down at 4-10 ℃;
(4) above-mentioned colostrum W1/O is joined under 2000 rev/mins of stirring states in 400 milliliter 3% the polyvinyl alcohol, whipping temp is 5-30 ℃, and mixing time is 0.2 hour, makes emulsion W1/O/W2, preserves down at 4-10 ℃;
(5) emulsion W1/O/W2 is joined in the 2%NaCl aqueous solution of 3 times of emulsion volumes, makes organic solvent volatilization by 800 rev/mins of stirrings, then 1800 rev/mins centrifugal 10 minutes, collect microsphere, deposit in refrigerator and cooled and hide.
Prepared chicken interferon microsphere form rounding, even particle size distribution, mean diameter are at 18.4 microns, and drug loading can reach 7.9%, and envelop rate is 30.0%, and extracorporeal releasing experiment shows that slow release can reach for 3 weeks, meets the durative action preparation feature.Zoopery proves this new forms of interferon except that the anti-fowl disease toxic action with interferon, and its half-life in vivo is 5.6 times of common chicken interferon, thereby has prolonged its action time in vivo.
Above-mentioned detailed description of the preparation method of this chicken interferon long-acting sustained-release dosage form being carried out with reference to embodiment; be illustrative rather than determinate; can list several embodiment according to institute's limited range; therefore in the variation and the modification that do not break away under the general plotting of the present invention, should belong within protection scope of the present invention.
Claims (5)
1, a kind of preparation method of chicken interferon long-acting sustained-release dosage form is characterized in that comprising the steps:
(1) a certain amount of chicken interferon is dissolved in the PBS buffer solution that contains stabilizing agent, makes aqueous phase solution (W1), the content of chicken interferon is 0.5-50 mg/ml;
(2) hand over fat/glycolide copolymer to make oil-phase solution (0) with the dichloromethane dissolving with third, the content of third friendship fat/glycolide copolymer is 0.1-0.5 grams per milliliter; The above-mentioned aqueous phase solution (W1) that contains chicken interferon is joined in the oil-phase solution (0), oil-phase solution (0) is 20: 1 to 2: 1 with the ratio of aqueous phase solution (W1), these two kinds of solution are stirred down for 5-30 ℃ in temperature, mixing speed is 500-8000 rev/mins, mixing time is 0.02-0.2 hour, mix homogeneously; Make colostrum W1/0, preserve down at 4-10 ℃;
(3) polyvinyl alcohol fully is dissolved in water and makes aqueous phase solution (W2), the weight concentration of polyvinyl alcohol is 0.5-50%; Above-mentioned colostrum W1/0 is joined aqueous phase solution (W2) stir, whipping temp is 5-30 ℃, and mixing speed is 100-3000 rev/mins, and mixing time is 0.2-0.5 hour; The ratio of colostrum W1/0 and aqueous phase solution (W2) is 1: 50 to 1: 200, makes emulsion W1/0/W2, preserves down at 4-10 ℃;
(4) emulsion W1/0/W2 is transferred in the NaCl aqueous solution of 1-5%, stir, whipping temp is 5-30 ℃, and mixing speed is 500-3000 rev/mins, and mixing time is 0.2-0.5 hour, makes the organic solvent volatilization, centrifugal then collection microsphere;
(5) in order to keep the stable of solution, add certain amount of stabilizer, stabilizing agent directly joins in described preparation process (1) solution.
2, the preparation method of chicken interferon long-acting sustained-release dosage form according to claim 1 is characterized in that described third friendship fat/glycolide molecular weight of copolymer is 2000-5000Da.
3, the preparation method of chicken interferon long-acting sustained-release dosage form according to claim 1 is characterized in that described stabilizing agent is selected from one or more of trehalose, bovine serum albumin and Polyethylene Glycol.
4, the preparation method of chicken interferon long-acting sustained-release dosage form according to claim 1, the addition that it is characterized in that described stabilizing agent is 0.1%-10% of a final solution.
5, the preparation method of chicken interferon long-acting sustained-release dosage form according to claim 1 is characterized in that described chicken interferon is reorganization chicken genetic engineering interferon IFN-α, IFN-β and the natural LeIF of chicken.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008100534107A CN101411870A (en) | 2008-06-03 | 2008-06-03 | Method for preparing chicken interferon long-acting sustained-release dosage form |
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008100534107A CN101411870A (en) | 2008-06-03 | 2008-06-03 | Method for preparing chicken interferon long-acting sustained-release dosage form |
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| CN101411870A true CN101411870A (en) | 2009-04-22 |
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| CNA2008100534107A Pending CN101411870A (en) | 2008-06-03 | 2008-06-03 | Method for preparing chicken interferon long-acting sustained-release dosage form |
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Application publication date: 20090422 |