CN101297962A - Preparation of pig interferon novel dosage form - Google Patents
Preparation of pig interferon novel dosage form Download PDFInfo
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- CN101297962A CN101297962A CNA200810053366XA CN200810053366A CN101297962A CN 101297962 A CN101297962 A CN 101297962A CN A200810053366X A CNA200810053366X A CN A200810053366XA CN 200810053366 A CN200810053366 A CN 200810053366A CN 101297962 A CN101297962 A CN 101297962A
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Abstract
The invention relates to a preparation method of a new formulation pig interferon, which has the steps as follows: (1) the pig interferon is dissolved in an aqueous phase buffer solution to form a solution (A), the pH value of which ranges from 2.5 to 7.0 and the content of the pig interferon is 0.5-5.0 mg/ml; (2) the acid solution (A) containing the pig interferon is added into a liquid nonionic type surfactant solution, the hydrophile-lyophile balance value of which is HLB being more than or equal to 9 and less than or equal to 15, or into amphipathic grease, or into the intermixture of the nonionic type surfactant solution and the amphipathic grease to be mixed as a solution (B); (3) the solution (B) is added into liquid oil phase with the hydrophile-lyophile balance value of HLB being more than or equal to 0 and less than or equal to 9, or into a lipophilic emulsifier, or into the intermixture of the oil phase and the lipophilic emulsifier. The ratio of the solution (B) and the mixture ranges from 1:1 to 1:9 and the two solutions are stirred and mixed at the temperature of 5 DEG C to 30 DEG C to form an oil phase formulation (C); (4) a stabilizing agent is added. The preparation method of the invention has simple preparation, simple and convenient application and easy absorption, and can better realize the effect of treating pig viral diseases.
Description
Technical field
The invention belongs to the preparing technical field of bio-pharmaceutical, particularly a kind of preparation method of pig interferon novel dosage form.
Background technology
At present, pig interferon all is with the administration of injecting better therapeutic effect to be arranged, and many persons need inject 1-2 time every day, brings a lot of inconvenience for the use of culturing the owner, and therefore being made into drinking-water, oral formulations just becomes the target that people pursue.If have breakthrough in this regard, will produce huge social and economic benefit.But directly with these bio-pharmaceutical drinking-water, oral, because the degraded digestion of gastrointestinal tract endoenzyme and the absorption barrier of intestinal make its availability very low, therapeutic effect is relatively poor.
Therefore, providing a kind of preparation method of pig interferon novel dosage form, effectively prevent and prevent and treat various pig virus 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 pig interferon novel dosage form.
A kind of preparation method of pig interferon novel dosage form is characterized in that comprising the steps:
(1) a certain amount of pig interferon is dissolved in the water buffer solution, the pH value of this solution (A) is 2.5-7.0, and the content of pig interferon is the 0.5-5.0 mg/ml;
(2) the above-mentioned acid solution (A) that contains pig interferon is joined in the nonionic surfactant solution of liquid state that hydrophile-lipophile balance value (HLB) is 9≤HLB≤15, or in the amphiphilic grease, or in their mixed liquor; Described solution (A) and these surfactants, or amphiphilic grease, or the ratio of their mixed liquor is 1: 4 to 1: 40; These two kinds of solution stir under temperature 5-30 ℃, and it is mixed uniformly, become a kind of transparent solution (B);
(3) solution (B) is added in the oil phase of liquid state that hydrophile-lipophile balance value is 0≤HLB≤9, or in the lipophilic emulsifier, or in the mixed liquor of oil phase and lipophilic emulsifier, solution (B) is 1: 1 to 1: 9 with its ratio, these two kinds of solution are mixed under temperature 5-30 ℃, finally become a kind of transparent oil phase formulation (C), preserve down at 4-10 ℃;
(4) in order to keep the stable of solution, add certain amount of stabilizer; Stabilizing agent directly joins in described preparation process (1) solution, in the solution in the perhaps described step (3).
Surfactant in the described step (2), or amphiphilic grease, or their mixed liquor adopts following one or more mixing: ten Monooctamoins, Polyethylene Glycol-8-glycerol are sad/decanoin, Tween 80.
Described mixing speed is 100-1800 rev/min, and mixing time is 0.4-4 hour.
Lipophile solution or emulsifying agent in the described step (3) are: glyceryl oleate, polyglycereol-3-oleate, Polyethylene Glycol-6-glycerin mono-fatty acid ester.
Whipping temp in the described step (3) is 5-30 ℃, and mixing speed is 100-1800 rev/min, and mixing time is 0.4-4.0 hour.
Described stabilizing agent is selected from one or more of trehalose, bovine serum albumin, porcine hemoglobin and Polyethylene Glycol.
The addition of described stabilizing agent is the 0.1%-10% of final solution.
Described pig interferon is reorganization pig genetic engineering interferon IFN-α, IFN-β and the natural LeIF of pig.
The beneficial effect of the inventive method is: it is simple to have preparation technology, realize easily, it is convenient to use, characteristics such as required cost is low, this method adopts toxicity little, materials such as oral safe dispersant and oil phase make the uniform dispersing and dissolving of pig interferon in oil phase, finally become a kind of transparent pig interferon oil phase formulation.The oil phase formulation experiment in vitro that adopts this method to make shows that it in different pH (2-11) solution emulsification can both take place, and pig interferon still is wrapped in basically in the oil and does not enter water.Therefore at drinking-water, when oral, Degradation that can reasonable opposing gastrointestinal enzyme, and absorbing is easily better brought into play the antiviral drug effect.
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 pig interferon novel dosage form is characterized in that concrete implementation step is as follows:
(1) is to add 32.0mg pig genetic engineering interferon IFN-α in 4.5 the solution at 8ml pH, makes its dissolving (A solution);
(2) taking polyethylene glycol-8-glycerol sad/decanoin 40.0ml, A solution added mix into 48ml.Mixing speed: 500 rev/mins; Time: 3.0 hours; Temperature: 20 ℃ (B solution);
(3) get polyglycereol-3-oleate 152ml, the adding of B solution is mixed into 200ml, mixing speed: 500 rev/mins, the time: 3.0 hours, temperature: 20 ℃ (C solution);
(4) add 500mg trehalose and 500mg porcine hemoglobin at C solution; And mix homogeneously, deposit in refrigerator and cooled and hide.
Embodiment 2
A kind of preparation method of pig interferon novel dosage form is characterized in that concrete implementation step is as follows:
(1) in the solution of 10ml pH=3.5, adds the natural LeIF 16.0mg of pig, make its dissolving (solution A);
(2) get Tween 80 14ml, ten Monooctamoin 26ml, mix homogeneously adds solution A then and mixes, and stirs; Mixing speed: 1000 rev/mins; Time: 2.5 hours; Temperature: 18 ℃ (solution B);
(3) get glyceryl oleate 150ml, above-mentioned B solution adding is mixed into 200ml; Mixing speed: 1000 rev/mins; Time: 2.5 hours; Temperature: 18 ℃ (C solution);
(4) add 100mg trehalose and 200mg bovine serum albumin in C solution, mix homogeneously is deposited in refrigerator and cooled and is hidden.
Embodiment 3
A kind of preparation method of pig interferon novel dosage form is characterized in that concrete implementation step is as follows:
(1) add 50.0mg pig genetic engineering interferon IFN-β in the solution of 10ml pH=4,200mg Polyethylene Glycol 5000 makes its dissolving (A solution);
(2) taking polyethylene glycol-8-glycerol sad/decanoin 80ml; A solution is added, be mixed into 90ml; Mixing speed: 1500 rev/mins; Time: 2 hours; Temperature: 25 ℃ (B solution);
(3) get polyglycereol 3 oleate 55ml and Polyethylene Glycol-6-glycerol list olein 55ml, be mixed into 110ml solution, then B solution is mixed mixing speed with this mixed liquor under following condition: 1500 rev/mins; Time: 2 hours; Temperature: 25 ℃ (C solution), deposit in refrigerator and cooled and hide, preserve down at 4-10 ℃.
Application example 1
Pig interferon novel dosage form is to the therapeutical effect of transmissible gastroenteritis of swine
Therapeutic test makes young pig that transmissible gastroenteritis of swine take place with the method for artificial infected pigs Transmissible gastroenteritis virus the pig of 20 10-20 ages in days in artificial Causative virus model, and the while is divided into 2 groups, 10 every group at random.The A group is " pig interferon novel dosage form " treatment group, and pig interferon novel dosage form is to adopt the preparation of embodiment 1 method; The B group is treated with normal saline for matched group.2 groups of pigs are contaminated with transmissible gastro-enteritis virus simultaneously, every pig is with the strong malicious intramuscular injection 0.5ml of transmissible gastro-enteritis virus, after waiting clinical symptoms to occur, give " pig interferon novel dosage form " 1.0ml/ head to the A group with water way, once a day, logotype 2-3 days, B group pig injecting normal saline 1.0ml/ head, once a day, logotype 2-3 days, observe morbidity death and the pathological change of pig then, and itemized record.
The artificial therapeutic effect that causes a disease
Behind the contamination 24h, test pig begins to occur clinical symptoms: lassitude, to stand transfixed to the ground, passage of loose stools, and diet reduces or is useless exhausted.After the medication, A group pig takes a turn for the better since the 2d state of an illness, and 3d has dead pig to occur, the basic rehabilitation of the pig that survives behind the 4d, and sb.'s illness took a turn for the worse after the 2nd day symptom occurring for B group pig, and it is dead to begin appearance, spontaneous recovery behind the not dead pig 6d.Pig interferon novel dosage form treatment group and matched group difference is (P＜0.01) extremely significantly, illustrates that water way gives " pig interferon novel dosage form " transmissible gastroenteritis of swine is had certain therapeutical effect.
Table 1 liang group therapeutic outcome comparison (example, %)
| Group | The example number | Cure | Take a turn for the better | Effectively | Invalid and dead |
| The A group | 10 | 3(30.0％) | 6(60.0％) | 9(90.0％) | 1(10.0％) |
| The B group | 10 | 1(10.0％) | 3(30.0％) | 4(40％) | 6(60.0％) |
Application example 2
Pig interferon novel dosage form is to the therapeutical effect of porcine epizootic diarrhea
Typical porcine epizootic diarrhea morbidity pig is selected in the clinical treatment test, and 27 pigs are divided into 3 groups at random, and the A group gives pig interferon novel dosage form 0.2ml/ head with the spice oral way, and pig interferon novel dosage form is to adopt the preparation of embodiment 2 methods; B group injection astragalus polysaccharides 5mg/ head.C organizes oral normal saline.
Experimental result
Table 2 " pig interferon novel dosage form " treatment Porcine Epidemic Diarrhea result of the test
| Group | Quantity | The morbidity number | Invalid number | Inefficiency % | Significant figure | Effective percentage % |
| The A group | 9 | 9 | 1 | 11.1 | 8 | 88.9 |
| The B group | 9 | 9 | 6 | 66.7 | 3 | 33.3 |
| The C group | 9 | 9 | 8 | 88.9 | 1 | 11.1 |
By table 2 as seen, " pig interferon novel dosage form " test group effective percentage is 88.9%, and the effective percentage of oral normal saline group is 11.1%.As seen, give pig interferon novel dosage form with the spice oral way porcine epizootic diarrhea is had good therapeutic effect.Experiment showed, explanation spice orally give pig interferon novel dosage form may command Porcine Epidemic Diarrhea feelings.
Pig interferon novel dosage form mainly has significant advantage to treatment pig virus prevention and treatment of diseases.Studies confirm that: pig interferon novel dosage form also has remarkable therapeutical effect to pig model and the porcine epizootic diarrhea morbidity pig of artificial challenge transmissible gastro-enteritis virus.As seen, give the active drug that pig interferon novel dosage form is a treatment pig virus disease with drinking-water, oral way.
Above-mentioned detailed description of the preparation method of this pig interferon novel 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 (6)
1, a kind of preparation method of pig interferon novel dosage form is characterized in that comprising the steps:
(1) a certain amount of pig interferon is dissolved in the water buffer solution, the pH value of this solution (A) is 2.5-7.0, and the content of pig interferon is the 0.5-5.0 mg/ml;
(2) the above-mentioned acid solution (A) that contains pig interferon is joined in the nonionic surfactant solution of liquid state that hydrophile-lipophile balance value (HLB) is 9≤HLB≤15, or in the amphiphilic grease, or in their mixed liquor; Described solution (A) and these surfactants, or amphiphilic grease, or the ratio of their mixed liquor is 1: 4 to 1: 40; These two kinds of solution stir under temperature 5-30 ℃, and it is mixed uniformly, become a kind of transparent solution (B);
(3) solution (B) is added in the oil phase of liquid state that hydrophile-lipophile balance value is 0≤HLB≤9, or in the lipophilic emulsifier, or in the mixed liquor of oil phase and lipophilic emulsifier, solution (B) is 1: 1 to 1: 9 with its ratio, these two kinds of solution are mixed under temperature 5-30 ℃, finally become a kind of transparent oil phase formulation (C), preserve down at 4-10 ℃;
(4) in order to keep the stable of solution, add certain amount of stabilizer; Stabilizing agent directly joins in described preparation process (1) solution, in the solution in the perhaps described step (3).
2, the preparation method of pig interferon novel dosage form according to claim 1, it is characterized in that the surfactant in the described step (2), or amphiphilic grease, or their mixed liquor adopts following one or more mixing: Polyethylene Glycol-8-glycerol is sad/and decanoin, Tween 80, ten Monooctamoins.
3, the preparation method of pig interferon novel dosage form according to claim 1 is characterized in that lipophile solution or the emulsifying agent in the described step (3) is: glyceryl oleate, polyglycereol-3-oleate, Polyethylene Glycol-6-glycerin mono-fatty acid ester.
4, the preparation method of pig interferon novel dosage form according to claim 1 is characterized in that described stabilizing agent is selected from one or more of trehalose, bovine serum albumin, porcine hemoglobin and Polyethylene Glycol.
5, the preparation method of pig interferon novel dosage form according to claim 1, the addition that it is characterized in that described stabilizing agent is the 0.1%-10% of final solution.
6, the preparation method of pig interferon novel dosage form according to claim 1 is characterized in that described pig interferon is reorganization pig genetic engineering interferon IFN-α, IFN-β and the natural LeIF of pig.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810053366XA CN101297962A (en) | 2008-05-30 | 2008-05-30 | Preparation of pig interferon novel dosage form |
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| Application Number | Priority Date | Filing Date | Title |
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| CNA200810053366XA CN101297962A (en) | 2008-05-30 | 2008-05-30 | Preparation of pig interferon novel dosage form |
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| CN101297962A true CN101297962A (en) | 2008-11-05 |
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| CNA200810053366XA Pending CN101297962A (en) | 2008-05-30 | 2008-05-30 | Preparation of pig interferon novel dosage form |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112457391A (en) * | 2020-11-02 | 2021-03-09 | 天津大学 | Method for co-secretion expression of porcine interferon alpha, beta and lambda 1 in saccharomyces cerevisiae and application thereof |
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2008
- 2008-05-30 CN CNA200810053366XA patent/CN101297962A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112457391A (en) * | 2020-11-02 | 2021-03-09 | 天津大学 | Method for co-secretion expression of porcine interferon alpha, beta and lambda 1 in saccharomyces cerevisiae and application thereof |
| CN112457391B (en) * | 2020-11-02 | 2022-10-04 | 天津大学 | Method for co-secretion expression of porcine interferon alpha, beta and lambda 1 in saccharomyces cerevisiae and application thereof |
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Open date: 20081105 |