CN101632634B - N(2)-L-alanyl-L-glutamine liposome injection and preparation method thereof - Google Patents
N(2)-L-alanyl-L-glutamine liposome injection and preparation method thereof Download PDFInfo
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Abstract
The invention provides an N(2)-L-alanyl-L-glutamine liposome injection and a preparation method thereof. The N(2)-L-alanyl-L-glutamine liposome injection is made of N(2)-L-alanyl-L-glutamine liposome and random existent auxiliary materials. The N(2)-L-alanyl-L-glutamine liposome is prepared form the following components by weight: 1 part of N(2)-L-alanyl-L-glutamine, 5-25 parts of phospholipid, 1-3 parts of cholesterol, 5-35 parts of poloxamer 188 and 0.5-2 parts of sodium deoxycholate. The invention overcomes the defect of the poor stability of the N(2)-L-alanyl-L-glutamine liposome injection in the prior art and reduces the cost of the preparation.
Description
Technical field
The present invention relates to a kind of Liposomal formulation, be specifically related to N (2)-L-alanyl-L-glutamine lipidosome injection and preparation method thereof, belong to medical technical field.
Background technology
N (2)-L-alanyl-L-glutamine is an ingredient of parenteral nutrition, have the positive nitrogen balance of promotion, the anabolic effect of regulating muscle albumen, can prevent that the small intestinal mucosa permeability that causes because of long-term parenteral nutrition from strengthening and atrophy, and improving immunocompetence and prevent bacteremic generation.N (2)-L-alanyl-L-glutamine can be decomposed into-glutamine and alanine in vivo, and its characteristic can be replenished-glutamine via the parenteral nutrition transfusion.This pair of peptide decomposes the aminoacid that discharges and is stored in the corresponding site of health separately and carries out metabolism with the needs of body as nutrient substance.To occurring in the body-disease of the depletion of glutamine, can use this product and carry out the parenteral nutrition support.
At present, the dosage form of this kind list marketing has infusion solution and injectable powder, N (2)-L-alanyl-L-glutamine less stable, the long-term placement easily of solution state decomposed, and the aseptic powder preparation of listing, divide process of assembling higher to environmental requirement, it is higher to prepare aseptic cost of material, is difficult to reach aseptic requirement.
The preparation method of a kind of N (2)-L-alanyl-L-glutamine sterile powder injection is disclosed at Chinese patent CN100428931C, it carries out aseptic refining to N (2)-L-alanyl-L-glutamine and mannitol respectively, obtain aseptic crude drug, mix packing again.This method too complex, aseptic refining cost height, and add the purpose that mannitol can not play protection N (2)-L-alanyl-L-glutamine stability.
Liposome (liposomes) is dispersed in phospholipid by Britain scholar Bangham and Standish at first and finds when carrying out electron microscopic observation in the water.Phospholipid is dispersed in and forms multilamelar vesicles, every layer of bilayer that is lipid in the water naturally; Separated by water between vesicle central authorities and each layer, the about 4nm of bilayer thickness, the bimolecular folliculus with this similar biofilm structure became liposome afterwards.
Liposome research is that liposome is meant that the earliest the natural grease compounds is suspended in the vesicle with double seal structure that forms in the water, now also can be prepared by the phosphatide cpd of synthetic when previous very active field.People such as late 1960s Rahman at first use liposome as pharmaceutical carrier, in recent years, continuous progress along with biotechnology, liposome preparation technology is progressively perfect, the liposome mechanism of action is further illustrated, liposome is fit to vivo degradation, avirulence and non-immunogenicity in addition, and particularly great number tested data proof liposome can improve the Drug therapy index, reduces drug toxicity and reduce drug side effect as pharmaceutical carrier, and reduces advantage such as drug dose.
Summary of the invention
Decompose at long-term the placement easily of present N (2)-L-alanyl-L-glutamine solution, injectable powder requires the problem high, that preparation cost is high, the object of the present invention is to provide a kind of N (2)-L-alanyl-L-glutamine lipidosome injection, wrap up with liposome by reverse phase evaporation, solved the problem of above-mentioned existence.
The technical scheme that the present invention solves is as follows:
The invention provides a kind of N (2)-L-alanyl-L-glutamine lipidosome injection, it is characterized in that making by N (2)-L-alanyl-L-glutamine liposome and the optional adjuvant that exists.
The above-mentioned described N of the present invention (2)-L-alanyl-L-glutamine lipidosome injection, wherein said N (2)-L-alanyl-L-glutamine liposome is to be made by the component of following weight portion: 1 part of N (2)-L-alanyl-L-glutamine, phosphatidase 15～25 part, 1～3 part in cholesterol, 1885～35 parts of poloxamers, 0.5～2 part of NaTDC.
As preferably, above-mentioned described N (2)-L-alanyl-L-glutamine lipidosome injection, wherein said N (2)-L-alanyl-L-glutamine liposome is to be made by the component of following weight portion: 1 part of N (2)-L-alanyl-L-glutamine, 8～22.5 parts in phospholipid, 1.2～2 parts in cholesterol, 1886～30 parts of poloxamers, 0.8～1.5 part of NaTDC.
If desired, the above-mentioned described N of the present invention (2)-L-alanyl-L-glutamine lipidosome injection, wherein said N (2)-L-alanyl-L-glutamine liposome can also comprise makes pH value be adjusted to 5.0～7.0 pharmaceutically acceptable buffer salt solution.Described buffer salt is not particularly limited, and for example buffer salt solution is selected from one or more in phosphate buffer, citrate buffer, carbonate buffer solution, borate buffer solution, the acetate buffer.
If desired, the above-mentioned described N of the present invention (2)-L-alanyl-L-glutamine lipidosome injection, wherein said N (2)-L-alanyl-L-glutamine liposome can also comprise the isoosmotic adjusting agent of 4.5～25 weight portions.Described isoosmotic adjusting agent, for regulating the solution that medicinal liquid and blood plasma have identical osmotic pressure, the osmotic pressure in the above infusion preparation of 50ml should be etc. and to ooze or higher oozing, and can not cause any ANOMALOUS VARIATIONS of hemogram.Osmotic pressure regulator commonly used has sodium chloride, glucose, glycerol, mannitol, sorbitol, potassium chloride, sodium lactate, amino acids, dextran, gelatin, polyvidone class, starch derivatives etc., and the osmotic pressure regulator among the present invention is not particularly limited.Preferred described isoosmotic adjusting agent is selected from one or more in sodium chloride, glucose, mannitol, sorbitol, the glycerol.
The above-mentioned described N of the present invention (2)-L-alanyl-L-glutamine lipidosome injection, wherein said N (2)-L-alanyl-L-glutamine liposome is to be made by the method that comprises the steps: (1) is dissolved in phospholipid, cholesterol, NaTDC and poloxamer 188 in the organic solvent, gets organic facies; (2) with N (2)-L-alanyl-L-glutamine and/or isoosmotic adjusting agent is water-soluble or buffer salt solution in, water; (3) above-mentioned organic facies and water are mixed, stir, form w/o type Emulsion, the heated and stirred evaporation, when mixture reaches the thickness state, add suitable quantity of water or buffer salt solution again, continue the heated and stirred evaporation and remove residual organic solvent, ultrasonic, be transferred in the at a high speed even matter blender, stir even matter, become suspension, promptly.
Wherein, described organic solvent for example can be selected from chloroform, ethanol, methanol, the tert-butyl alcohol, n-butyl alcohol, isopropyl alcohol, acetone, ether, benzyl alcohol, the normal hexane one or more.
Phospholipid is a kind of lipid that contains phosphoric acid, is amphiphilic substance, is biomembranous important component, emulsifying agent and surfactant.Phospholipid can be divided into phosphoglyceride and sphingomyelins according to the difference of skeleton, and wherein, phosphoglyceride can be divided into phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, Phosphatidylserine, phosphatidylinositols, phosphatidyl glycerol, phosphoglyceride acid etc. again.The above-mentioned described N of the present invention (2)-L-alanyl-L-glutamine lipidosome injection, wherein said phospholipid is meant phosphatidylcholine, can be in soybean lecithin, Ovum Gallus domesticus Flavus lecithin, two stearic acid lecithin, two palmitic acid lecithin, two myristic acid lecithin, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline, distearoyl phosphatidylcholine, the dipalmitoyl phosphatidyl choline one or more.
As one of embodiment, N of the present invention (2)-L-alanyl-L-glutamine lipidosome injection, it is an injection, be by resulting suspension after filtration, packing, sterilization, N (2)-L-alanyl-L-glutamine lipidosome injection.
As another embodiment; N of the present invention (2)-L-alanyl-L-glutamine lipidosome injection; it is a lyophilized preparation; the water-soluble back of the freeze drying protectant of 20～25 weight portions is added in the resulting suspension; stirring and evenly mixing; filter, lyophilization gets N (2)-L-alanyl-L-glutamine liposome freeze-drying agent.
Wherein said freeze drying protectant is not particularly limited, and can be the freeze drying protectant of pharmaceutics routine, for example is selected from one or more of mannitol, glucose, trehalose, lactose, sucrose, sorbitol, sodium chloride, glycine.
N provided by the invention (2)-L-alanyl-L-glutamine lipidosome injection carries out stability test and investigates, and places 10 days under 60 ℃ of high temperature, illumination 4500Lx condition, and every detection index has no significant change; Accelerated test is 6 months under 40 ℃ of high temperature, relative humidity 75% ± 5% condition, and every detection index does not have significant change; Long term test is 18 months under 25 ℃ of high temperature, relative humidity 60% ± 10% condition, and every detection index does not have significant change.
N provided by the invention (2)-L-alanyl-L-glutamine lipidosome injection carries out acute toxicity test, abnormal toxicity test and heat source check, and is all up to specification, and safety obtains proof.
N provided by the invention (2)-L-alanyl-L-glutamine lipidosome injection, by specific adjuvant and supplementary material proportioning, N (2)-L-alanyl-L-glutamine is made injection after making liposome, compared with prior art, have beyond thought effect, major advantage is as follows:
(1) N (2)-L-alanyl-L-glutamine is wrapped in the liposome, has improved the stability in the aqueous solution greatly, has guaranteed product quality;
(2) N (2)-L-alanyl-L-glutamine liposome freeze-drying agent is compared with the aseptic powder preparation and have been reduced cost and environmental requirement, has improved bioavailability;
(3) pharmaceutical carrier liposome vivo degradation, avirulence and non-immunogenicity, and can improve the Drug therapy index, reduce drug toxicity and reduce drug side effect;
(4) adopt conventional process equipment, but commercial scale, high efficiency production, and constant product quality is a kind of uniqueness and blanket, the low-cost industrial preparation method.
The specific embodiment
Further specify the present invention by the following examples, but should not be construed as limitation of the present invention.
Embodiment 1
The preparation of N (2)-L-alanyl-L-glutamine lipidosome injection
Prescription (100 bottles): N (2)-L-alanyl-L-glutamine 10g
Soybean lecithin 120g
Cholesterol 20g
Poloxamer 188 300g
NaTDC 15g
Sodium chloride 45g
Preparation technology
(1) 120g soybean lecithin, 20g cholesterol, 15g NaTDC and 300g poloxamer 188 are dissolved in the ethanol of 800ml;
(2) N (2)-L-alanyl-L-glutamine 10g and sodium chloride 45g are dissolved in the phosphoric acid-disodium hydrogen phosphate buffer solution of 2000mlpH value 5.0;
(3) with the two mixing, stir, form w/o type Emulsion, the heated and stirred evaporation is when mixture reaches the thickness state, phosphoric acid-sodium hydrogen phosphate the buffer that adds 3000mlpH value 5.0 again, continue the heated and stirred evaporation and remove residual ethanol, ultrasonic 30min is transferred in the at a high speed even matter blender, stir even matter 30min, get suspension;
(4) with the above-mentioned suspension that obtains after filtration, packing, sterilization, N (2)-L-alanyl-L-glutamine lipidosome injection.
Comparative Examples 1
The preparation of N (2)-L-alanyl-L-glutamine lipidosome injection
Prescription (100 bottles): N (2)-L-alanyl-L-glutamine 10g
Soybean lecithin 260g
Cholesterol 35g
Poloxamer 188 45g
NaTDC 4.8g
Sodium chloride 45g
Preparation technology
(1) 260g soybean lecithin, 35g cholesterol, 4.8g NaTDC and 45g poloxamer 188 are dissolved in the ethanol of 800ml;
(2) N (2)-L-alanyl-L-glutamine 10g and sodium chloride 45g are dissolved in the phosphoric acid-disodium hydrogen phosphate buffer solution of 2000mlpH value 5.0;
(3) with the two mixing, stir, form w/o type Emulsion, the heated and stirred evaporation is when mixture reaches the thickness state, phosphoric acid-sodium hydrogen phosphate the buffer that adds 3000mlpH value 5.0 again, continue the heated and stirred evaporation and remove residual ethanol, ultrasonic 30min is transferred in the at a high speed even matter blender, stir even matter 30min, get suspension;
(4) with the above-mentioned suspension that obtains after filtration, packing, sterilization, N (2)-L-alanyl-L-glutamine lipidosome injection.
Embodiment 2
The preparation of N (2)-L-alanyl-L-glutamine lipidosome injection
Prescription (100 bottles): N (2)-L-alanyl-L-glutamine 20g
Ovum Gallus domesticus Flavus lecithin 450g
Cholesterol 30g
Poloxamer 188 600g
NaTDC 20g
Glucose 500g
Preparation technology
(1) 450g Ovum Gallus domesticus Flavus lecithin, 30g cholesterol, 20g NaTDC and 600g poloxamer 188 are dissolved in the isopropyl alcohol of 2000ml;
(2) N (2)-L-alanyl-L-glutamine 20g and glucose 500g are dissolved in the citric acid-sodium citrate buffer solution of 5000mlpH value 7.0;
(3) with the two mixing, stir, form w/o type Emulsion, the heated and stirred evaporation is when mixture reaches the thickness state, citric acid-the sodium citrate buffer that adds 5000mlpH value 7.0 again, continue the heated and stirred evaporation and remove residual isopropanol, ultrasonic 30min is transferred in the at a high speed even matter blender, stir even matter 30min, get suspension;
(4) with the above-mentioned suspension that obtains after filtration, packing, sterilization, N (2)-L-alanyl-L-glutamine lipidosome injection.
Embodiment 3
The preparation of N (2)-L-alanyl-L-glutamine liposome freeze-drying agent
Prescription (100 bottles): N (2)-L-alanyl-L-glutamine 10g
Soybean lecithin 80g
Cholesterol 12g
Poloxamer 188 60g
NaTDC 8g
Mannitol 200g
Preparation technology
(1) 10g soybean lecithin, 12g cholesterol, 8g NaTDC and 60g poloxamer 188 are dissolved in the acetone of 500ml;
(2) N (2)-L-alanyl-L-glutamine 10g is dissolved in the phosphoric acid-dipotassium hydrogen phosphate buffer solution of 200mlpH value 6.0;
(3) with the two mixing, stir, form w/o type Emulsion, the heated and stirred evaporation is when mixture reaches the thickness state, phosphoric acid-dipotassium hydrogen phosphate the buffer that adds 200mlpH value 6.0 again, continue the heated and stirred evaporation and remove residual acetone, ultrasonic 30min is transferred in the at a high speed even matter blender, stir even matter 30min, get suspension;
(4) 200g mannitol is dissolved in 500ml water, adds in the above-mentioned suspension, stirring and evenly mixing filters, and lyophilization gets N (2)-L-alanyl-L-glutamine liposome freeze-drying agent.
Comparative Examples 2
The preparation of N (2)-L-alanyl-L-glutamine liposome freeze-drying agent
Prescription (100 bottles): N (2)-L-alanyl-L-glutamine 10g
Soybean lecithin 45g
Cholesterol 9g
Poloxamer 188 360g
NaTDC 22g
Mannitol 200g
Preparation technology
(1) 45g soybean lecithin, 9g cholesterol, 22g NaTDC and 360g poloxamer 188 are dissolved in the acetone of 500ml;
(2) N (2)-L-alanyl-L-glutamine 10g is dissolved in the phosphoric acid-dipotassium hydrogen phosphate buffer solution of 200mlpH value 6.0;
(3) with the two mixing, stir, form w/o type Emulsion, the heated and stirred evaporation is when mixture reaches the thickness state, phosphoric acid-dipotassium hydrogen phosphate the buffer that adds 200mlpH value 6.0 again, continue the heated and stirred evaporation and remove residual acetone, ultrasonic 30min is transferred in the at a high speed even matter blender, stir even matter 30min, get suspension;
(4) 200g mannitol is dissolved in 500ml water, adds in the above-mentioned suspension, stirring and evenly mixing filters, and lyophilization gets N (2)-L-alanyl-L-glutamine liposome freeze-drying agent.
Embodiment 4
The preparation of N (2)-L-alanyl-L-glutamine liposome freeze-drying agent
Prescription (100 bottles): N (2)-L-alanyl-L-glutamine 20g
Ovum Gallus domesticus Flavus lecithin 200g
Cholesterol 30g
Poloxamer 188 250g
NaTDC 20g
Mannitol 500g
Preparation technology
(1) 200g Ovum Gallus domesticus Flavus lecithin, 30g cholesterol, 20g NaTDC and 250g poloxamer 188 are dissolved in the ethanol of 800ml;
(2) N (2)-L-alanyl-L-glutamine 20g is dissolved in the acetic acid-sodium acetate buffer solution of 300mlpH value 5.6;
(3) with the two mixing, stir, form w/o type Emulsion, the heated and stirred evaporation is when mixture reaches the thickness state, acetic acid-the sodium-acetate buffer that adds 300mlpH value 5.6 again, continue the heated and stirred evaporation and remove residual ethanol, ultrasonic 30min is transferred in the at a high speed even matter blender, stir even matter 30min, get suspension;
(4) 500g mannitol is dissolved in 800ml water, adds in the above-mentioned suspension, stirring and evenly mixing filters, and lyophilization gets N (2)-L-alanyl-L-glutamine liposome freeze-drying agent.
Test example 1
The mensuration of envelop rate
Get the Liposomal formulation of embodiment preparation, the total content that high performance liquid chromatography detects N (2)-L-alanyl-L-glutamine is M, selects for use column chromatography to separate liposome.
Get 1.5g sephadex G-50, soak more than the swelling 12h with the pH6.8 phosphate buffer, pack in the chromatographic column (200 * 10mm) into, with above-mentioned phosphate buffer flushing balance, get N (2)-L-alanyl-L-glutamine Liposomal formulation that embodiment 1-4 and Comparative Examples 1-2 obtain respectively, be dissolved in water and make the solution that every 1ml contains N (2)-L-alanyl-L-glutamine 20mg, get 1.8ml adding chromatography respectively and live the top, with phosphate buffer 50ml eluting, flow velocity 1.0ml/min, the eluent of collecting adds rupture of membranes agent (ethanol: 50ml benzyl alcohol=6: 1), mixing, the content M of high performance liquid chromatography detection N (2)-L-alanyl-L-glutamine
1
Envelop rate %=M
1/ M * 100%.
Table 1 entrapment efficiency determination result
By above result as can be known, the liposome encapsulation that proportioning makes of writing out a prescription of the embodiment in the scope of the invention is very high, meets the actual production requirement substantially; And the liposome encapsulation that the outer Comparative Examples prescription proportioning of the scope of the invention makes is very low, has compared tangible gap with embodiment, is not suitable for production requirement.
Test example 2
The detection of particle diameter
Get the Liposomal formulation of embodiment 1-4 and Comparative Examples 1-2 preparation, adopt micro-image analyzer to measure the particle size distribution of liposome, result such as table 2:
Table 2 particle diameter testing result
By above result as can be known, it is spherical that the liposome that embodiment 1-4 makes shows, and particle diameter is even, and scope is 80-200nm; The liposome shape that Comparative Examples 1-2 makes is indefinite, disorderly and unsystematic, not of uniform size, and particle diameter is inhomogeneous, and scope is 300-800nm.
Test example 3
Quality research
With the sample of above each embodiment preparation and N (the 2)-L-alanyl-L-glutamine injection (ChongQing LaiMei Pharmacy Co., Ltd of listing, lot number 20070617) and N (2)-L-alanyl-L-glutamine injectable powder (Hainan Huanglong Pharmaceutical Co., Ltd produces, lot number 200801108) under 60 ℃ of high temperature, illumination 4500Lx condition, places and carried out the influence factor in 10 days and test investigation, the results are shown in Table 3; Under 40 ℃ of high temperature, relative humidity 75% ± 5% condition 6 months, carry out accelerated test and investigate, the results are shown in Table 4; Under 25 ℃ of high temperature, relative humidity 60% ± 10% condition 18 months, carry out long term test and investigate, detect the variation of every quality index, the results are shown in Table 5.
Table 3 influence factor result
Table 4 accelerated test result
Table 5 long-term test results
Quickened March, June by above found that, long-term December, N (the 2)-L-alanyl-L-glutamine clarity of injection of listing is against regulation 18 months the time, and pH value descends bigger, and content reduces obviously, and related substance raises; N (the 2)-L-alanyl-L-glutamine injectable powder clarity of listing is against regulation, and other indexs also change to some extent; And the sample appearance character of the present invention's preparation does not have significant change, and clarity, pH value, content and related substance do not have obvious variation yet.The sample stable quality after long time storage that the present invention's preparation is described is better.
The present invention is described according to preferred embodiment.Should be understood that the description of front and embodiment are just to illustrating the present invention.Under prerequisite without departing from the spirit and scope of the present invention, those skilled in the art can design multiple alternative of the present invention and improvement project, and it all should be understood to be within protection scope of the present invention.
Claims (10)
1. a N (2)-L-alanyl-L-glutamine lipidosome injection, it is characterized in that described N (2)-L-alanyl-L-glutamine liposome is to be made by the component of following weight portion: 1 part of N (2)-L-alanyl-L-glutamine, phosphatidase 15～25 part, 1～3 part in cholesterol, 1885～35 parts of poloxamers, 0.5～2 part of NaTDC.
2. N according to claim 1 (2)-L-alanyl-L-glutamine lipidosome injection, it is characterized in that described N (2)-L-alanyl-L-glutamine liposome is to be made by the component of following weight portion: 1 part of N (2)-L-alanyl-L-glutamine, 8～22.5 parts in phospholipid, 1.2～2 parts in cholesterol, 188 6～30 parts of poloxamers, 0.8～1.5 part of NaTDC.
3. according to each described N (2) of claim 1-2-L-alanyl-L-glutamine lipidosome injection, it is characterized in that described N (2)-L-alanyl-L-glutamine liposome also comprises to make pH value be adjusted to 5.0～7.0 pharmaceutically acceptable buffer salt solution.
4. N according to claim 3 (2)-L-alanyl-L-glutamine lipidosome injection is characterized in that described buffer salt solution is selected from one or more in phosphate buffer, citrate buffer, carbonate buffer solution, borate buffer solution, the acetate buffer.
5. according to each described N (2) of claim 1-2-L-alanyl-L-glutamine lipidosome injection, it is characterized in that described N (2)-L-alanyl-L-glutamine liposome also comprises the isoosmotic adjusting agent of 4.5～25 weight portions, described regulator is selected from one or more in sodium chloride, glucose, mannitol, sorbitol, the glycerol.
6. N according to claim 5 (2)-L-alanyl-L-glutamine lipidosome injection, it is characterized in that described N (2)-L-alanyl-L-glutamine liposome is to be made by the method that comprises the steps: (1) is dissolved in phospholipid, cholesterol, NaTDC and poloxamer 188 in the organic solvent, gets organic facies; (2) with N (2)-L-alanyl-L-glutamine and/or isoosmotic adjusting agent is water-soluble or buffer salt solution in, water; (3) above-mentioned organic facies and water are mixed, stir, form w/o type Emulsion, the heated and stirred evaporation, when mixture reaches the thickness state, add suitable quantity of water or buffer salt solution again, continue the heated and stirred evaporation and remove residual organic solvent, ultrasonic, be transferred in the at a high speed even matter blender, stir even matter, become suspension, promptly.
7. according to each described N (2) of claim 1-2-L-alanyl-L-glutamine lipidosome injection, wherein said phospholipid is selected from one or more in soybean lecithin, Ovum Gallus domesticus Flavus lecithin, two stearic acid lecithin, two palmitic acid lecithin, two myristic acid lecithin, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline, distearoyl phosphatidylcholine, the two palmityl phosphatidyl cholines.
8. N according to claim 6 (2)-L-alanyl-L-glutamine lipidosome injection, it is an injection, be by resulting suspension after filtration, packing, sterilization, N (2)-L-alanyl-L-glutamine lipidosome injection.
9. N according to claim 6 (2)-L-alanyl-L-glutamine lipidosome injection; it is a lyophilized preparation; the water-soluble back of the freeze drying protectant of 20～25 weight portions is added in the resulting suspension; stirring and evenly mixing; filter; lyophilization gets N (2)-L-alanyl-L-glutamine liposome freeze-drying agent.
10. N according to claim 9 (2)-L-alanyl-L-glutamine lipidosome injection, wherein said freeze drying protectant are selected from one or more of mannitol, glucose, trehalose, lactose, sucrose, sorbitol, sodium chloride, glycine.
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| CN105125497B (en) * | 2015-09-20 | 2018-11-20 | 南京恩泰医药科技有限公司 | A kind of preparation method of N (2)-Ala-Gln injection |
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