CN1160121C - Growth hormone liposome for pig and its preparation method - Google Patents
Growth hormone liposome for pig and its preparation method Download PDFInfo
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- CN1160121C CN1160121C CNB02112910XA CN02112910A CN1160121C CN 1160121 C CN1160121 C CN 1160121C CN B02112910X A CNB02112910X A CN B02112910XA CN 02112910 A CN02112910 A CN 02112910A CN 1160121 C CN1160121 C CN 1160121C
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- growth hormone
- liposome
- lecithin
- pig
- film material
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Abstract
The present invention relates to a growth hormone liposome for pigs and a preparation method thereof, which belongs to the technical field of biological medicines. The growth hormone liposome for pigs is a novel dosage form of growth hormone sustained-release preparation for pigs. The preparation method comprises that a bimolecular layer formed from adipoid for growth hormone for pigs is encapsulated with membrane material. The membrane material comprises the main components: lecithin, cholesterol and octadecanamine. The product has high encapsulation efficiency and has a long-acting slow release effect, and the slow release time of the product in the bodies of pigs is longer than or equal to 30 days. The present invention used for injection has the advantages of easy operation, practicality and convenience for large-scale popularization. Practice proves that the PST liposome can replace PST in productive practice for fattening pigs.
Description
Technical field
The present invention relates to a boar and use growth hormone liposome and preparation method thereof.Pig is that a kind of pig of novel form is used the growth hormone slow releasing preparation with growth hormone liposome, belongs to the biological medicine technology field.
Background technology
(Growth Hormone or Somatotropin are the peptide hormones that animal antepituitary oxyphil cell produces ST) to growth hormone, can improve Livestock Production power, and pig is had obvious and stable effect of increasing production.Utilize biotechnology in recent years, (Porcine Somatotropin PST) can carry out commercialization production to pig, and being used for pig industry will greatly influence production technology, economic benefit and consumption mode with growth hormone.
Somatotropin preparation and operation technique have following three kinds at present.
1. make buffer agent, use injection.
The growth hormone lyophilized preparation is stored in below-20 ℃, when using, is made into the solution that concentration is 5mg/ml earlier with bicarbonate buffer (PH9.4) at every turn, redilution during injection needs injection every day.
2. make slow releasing agent, use the heeling-in method.
By measures such as embeddings growth hormone is made slow releasing agent, carry out subdermal implantation behind the ear again, can every several all heeling-ins once, the PST of production long-acting slow-release implant preparation just be arranged, its heeling-in was slowly discharged for 4 weeks in pig ear as U.S. Monsanto Company.
3. immunization.
Growth hormone with a kind of animal injects in the another kind of animal body earlier, make the antibody of its generation to this growth hormone, again this antibody is injected to original animal, make the antibody that produces this antibody in its body, it is anti antibody, this anti antibody can keep the several months long in animal body, continues the effect of performance growth hormone.
Above-mentioned three kinds of time-consuming taking a lot of work of method, but also will perform the operation, use difficulty bigger, be difficult to large-scale promotion.
Summary of the invention
The purpose of this invention is to provide a boar and use growth hormone (PST) liposome and preparation method thereof.The PST liposome is that a kind of growth hormone slow releasing preparation of novel form has the long-acting slow-release effect, uses injection, and large-scale promotion is convenient in simple and easy practicality.
The PST liposome bilayer that to be PST constitute with lipoids is sealed for the film material and is formed.Main component as the liposome membrane material is a phospholipid.Phospholipid molecule is typical parents' molecule, makes liposome have amphipathic property, and therefore, liposome is as the carrier of medicine, and it seals scope is very wide, lipophilic substance, and amphiprotic substance and water-soluble substances can be encapsulated.Because of phospholipid is biomembranous constituent, have catabolic enzyme in the organism again, be easy to metabolism.Thereby liposome has biological degradability and biocompatibility again.Studies show that, liposome enter in the body mainly by reticuloendothelial system (reticularenolothelial system, RES) engulf and activate the autoimmune function of body and change the kinetic property of encapsulated medicine and body in distribute.Use injection, the pig body is gone in the intravenous injection of PST liposome after, make growth hormone performance slow release and long lasting effect.
PST liposome of the present invention, it is characterized in that bilayer that PST constitutes with lipoids is sealed for the film material forms, the main component of film material is the mixture of lecithin, cholesterol and 18-amine., its composition: PST: the film material is 1: 180-200 (weight ratio), film material main component is formed: lecithin: cholesterol: the percentage by weight of 18-amine. is 65-85%: 10-33%: 2-5%, also can add or not add phosphatidylcholine (DPPC) in the liposome.The weight proportion of DPPC and lecithin is 0.25: 1, adds or do not add vitamin E (V
E), V
EWith the weight proportion of lecithin be 5: 1, add or do not add trehalose and/or sucrose, the weight proportion of trehalose, sucrose and lecithin is 2: 1.Add V
EAnd sugar, can improve the non-oxidizability and the stability of liposome.Sugar also is simultaneously protective agent and the proppant in the freezing dry process.This PST liposome particle diameter≤500nm, envelop rate 〉=90%, pig sustained release profile in vivo test time 〉=30 day, 10 ℃ of biological activity effect duration 〉=1 year.
The preparation method of this PST liposome is
A. film material preparation
By 65-85%: 10-33%: the 2-5% weight ratio takes by weighing lecithin, cholesterol, 18-amine. and transfers to flask at the bottom of the garden, and the ratio that adds the 30ml ether in every gram film material approximately adds ether, treats that it dissolves fully.
The preparation of B.PST solution
1/180-200 (weight ratio) by film material amount takes by weighing PST, is dissolved in the disodium hydrogen phosphate buffer solution (PBS), and per 5 milligrams of PST are dissolved among about 25mlPBS, pours into after the dissolving at the bottom of the garden in the flask.
C. ultrasonic emulsification
With material ultrasonic emulsification in the flask at the bottom of the garden 5 minutes.
D. anti-phase reduction vaporization
Emulsion after ultrasonic is extremely gluey at 30-40 ℃ of following reduction vaporization, film forming, and the PBS that adds same amount again washes film fully, and reduction vaporization is to taking out ether fully again.
E. lyophilization
Products therefrom behind the anti-phase reduction vaporization at-65--70 ℃ following lyophilization 3-4 days, is formed tiny white powder acicular crystal after the lyophilizing, promptly get product P ST liposome.Get damp for anti-moisture absorption, need airtight preservation.
Advantage of the present invention is
The quasi-lipid film material of PST liposome, easily by catabolic enzyme metabolism in the organism, thereby have biological degradability and a biocompatibility, can activate the body autoimmune function after being gulped down saliva by the organism reticuloendothelial system, and change in the kinetic property of encapsulated medicine and the body and distribute, can optimize drug release characteristic, make it to have drug release rate that pig special procures and drug release time etc., make growth hormone performance slow release and long lasting effect.
Adopt the reverse-phase evaporation process, can remove contained organic solvent, make to have very high envelop rate, and can stand sterilization, this preparation method is suitable for suitability for industrialized production.
Adopt freezing dry process, liposome is existed with solid forms, overcome the unstability of liquid lipidosome, guarantee the stability in the long term store and be convenient to transportation, also be suitable for suitability for industrialized production.
In a word, this preparation has the long-acting slow-release effect, and the envelop rate height uses injection, and large-scale promotion is convenient in simple and easy practicality.
(injected once in 30 days by injection PST (injecting the 4mg/ head every day one time) and injection PST liposome, the 120mg/ head) compares with matched group, the result shows that PST and PST liposome are approaching to the growing and fattening pigs fertility performance, compare with matched group, all can significantly improve day increment, the price of deed of growing and fattening pigs and improve the carcass quality of pig, prove that fully the PST liposome can replace PST to be used for the production practices of growing and fattening pigs.
The specific embodiment
Embodiment 1
(1) take by weighing lecithin 0.7325g, cholesterol 0.1474g, 18-amine. 0.0326g is transferred to flask at the bottom of the garden;
(2) add the 30ml ether, treat that it dissolves fully;
(3) add 5mgPST and be dissolved among the 25mlPBS, pour at the bottom of the garden in the flask;
(4) ultrasonic 5min;
(5) reduction vaporization is to gluey, and film forming adds 25mlPBS film is washed fully;
(6) reduction vaporization is to extracting ether fully;
(7) at-65--70 ℃ lyophilization 3-4 days, promptly get white powder acicular crystal PST liposome product after the lyophilizing.
Embodiment 2
(1) takes by weighing lecithin 2.918g, cholesterol 0.589g, 18-amine. 0.134g, trehalose 5.84g, V
E14.59g, be transferred to flask at the bottom of the garden;
(2) 80ml that adds diethyl ether treats that it dissolves fully;
(3) add 0.020gPST and be dissolved among the 100mlPBS, pour at the bottom of the garden in the flask;
The ultrasonic 5min of (4) 40% intensity;
After (5) 30 ℃ of reduced pressure treatment, add 120mlPBS again film is washed fully, reduced pressure treatment is removed remaining trace solvent again;
(6) place after 30 minutes, insert-65-70 ℃ refrigerator 3-4 days.Get product.
Claims (2)
1. a boar is used growth hormone liposome, it is characterized in that bilayer that pig constitutes with lipoids with growth hormone is sealed for the film material forms, the main component of film material is a lecithin, the mixture of cholesterol and 18-amine., its composition: pig is used growth hormone: the film material is 1: 180-200 (W/W), film material main component is formed: lecithin: cholesterol: the percentage by weight of 18-amine. is 65%-85%: 10-33%: 2-5% (W/W), also add or do not add phosphatidylcholine in the liposome, the proportioning of phosphatidylcholine and lecithin is 0.25: 1 (W/W), add or do not add vitamin E, the proportioning of vitamin E and lecithin is 5: 1 (W/W), add or do not add trehalose and/or sucrose, the proportioning of trehalose and lecithin is 2: 1 (W/W), and the proportioning of sucrose and lecithin is 2: 1 (W/W).
2, a boar is used the preparation method of growth hormone liposome, it is characterized in that:
A, the preparation of film material
By 65-85%: 10-33%: the 2-5% weight ratio takes by weighing lecithin, cholesterol, 18-amine. and is transferred to flask at the bottom of the garden, and the ratio that adds the 30ml ether in every gram film material approximately adds ether, treats that it dissolves fully;
B, pig are prepared with growth hormone solution
Take by weighing pig by the 1/180-200 (W/W) of film material amount and use growth hormone, be dissolved in the disodium hydrogen phosphate buffer solution (PBS), per 5 milligrams of hormones are dissolved in the 25ml buffer solution approximately, pour into after the dissolving at the bottom of the garden in the flask;
C, ultrasonic emulsification
With material ultrasonic emulsification in the flask at the bottom of the garden 5 minutes;
D, anti-phase reduction vaporization
Emulsion after ultrasonic is extremely gluey at 30-40 ℃ of following reduction vaporization, film forming, and the PBS that adds same amount again washes film fully, and reduction vaporization is to taking out ether fully again;
E, cool lyophilizing are dry
Products therefrom behind the anti-phase reduction vaporization at-65--70 ℃ following lyophilization 3-4 days, is formed tiny white powder acicular crystal after the lyophilizing, promptly get the product pig and use growth hormone liposome, get damp the airtight preservation of need for preventing moisture absorption.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB02112910XA CN1160121C (en) | 2002-04-18 | 2002-04-18 | Growth hormone liposome for pig and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB02112910XA CN1160121C (en) | 2002-04-18 | 2002-04-18 | Growth hormone liposome for pig and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1380097A CN1380097A (en) | 2002-11-20 |
| CN1160121C true CN1160121C (en) | 2004-08-04 |
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ID=4742339
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB02112910XA Expired - Fee Related CN1160121C (en) | 2002-04-18 | 2002-04-18 | Growth hormone liposome for pig and its preparation method |
Country Status (1)
| Country | Link |
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| CN (1) | CN1160121C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188379B (en) * | 2010-03-18 | 2014-10-15 | 浙江海正药业股份有限公司 | Preparation method of drug-carrying liposome |
| CN112724260B (en) * | 2021-01-15 | 2021-11-30 | 安徽中起生物科技有限公司 | Liposome-encapsulated recombinant veterinary growth-promoting protein and preparation method and application thereof |
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2002
- 2002-04-18 CN CNB02112910XA patent/CN1160121C/en not_active Expired - Fee Related
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| CN1380097A (en) | 2002-11-20 |
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