CN102441160B - Thymosin alpha1 medicinal composition and preparation method thereof - Google Patents
Thymosin alpha1 medicinal composition and preparation method thereof Download PDFInfo
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Abstract
The invention which belongs to the technical field of medicinal preparations provides a thymosin alpha1 injection preparation medicinal composition. The thymosin alpha1 injection preparation medicinal composition comprises thymosin alpha1, a pharmaceutic adjuvant, a buffer and a proper amount of a pH conditioning agent. The invention also provides a preparation method of the thymosin alpha1 medicinal composition. The thymosin alpha1 injection preparation medicinal composition prepared with the preparation method of the invention, which has a substantially increased stability, is benefit for the circulation and the use of the medicine.
Description
Technical field:
The present invention relates to the Thymosin alpha 1 preparation, relate in particular to a kind of Thymosin alpha 1 injection agent medicine compositions.
Background technology:
Thymosin alpha 1 (Thymosin α 1), structural formula is immunostimulant shown in (I), the mechanism of action that is used for the treatment of chronic hepatitis B and enhance immunity system response is illustrated fully.Its aminoacid sequence is: AC-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-L ys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-A sn-OH.Multinomial in vitro tests shows, this product promotes the lymphocytic maturation of T by stimulating the peripheral blood lymphocyte mitogen, lymphokine levels such as interferon-ALPHA, interferon gamma and the interleukin-22 of T emiocytosis, interleukin-13 increased T cell surface lymphokine acceptor levels simultaneously after increase antigen or mitogen activated.This product also can be by to the activation of cd4 cell, strengthens allosome and from the human mixed lymphocyte reaction of body.The gathering of NK cell before this product may increase, and interferon can make its cytotoxicity strengthen.
Thymosin alpha 1 stability in common aqueous solution is very poor, and behind the subcutaneous injection, the patient can not feel like oneself, and Thymosin alpha 1 pharmaceutical composition stability provided by the present invention significantly increases, and is beneficial to circulation and the use of medicine, and accepts extensively for the patient.
Summary of the invention:
The objective of the invention is to overcome the deficiencies in the prior art, a kind of more stable Thymosin alpha 1 injection agent medicine compositions is provided.
For achieving the above object, the technical solution used in the present invention is:
A kind of Thymosin alpha 1 injection agent medicine compositions, it is characterized in that: comprise that it is 5.0-7.5 that Thymosin alpha 1 1-100mg/ml, adjuvant 10-150mg/ml, buffer 10-250mM and an amount of sodium hydroxide or hydrochloric acid are regulated pH value, wherein buffer agent is sulfate, citrate, phosphate, lactate or its mixture.
Wherein, described adjuvant comprises excipient, antioxidant and local analgesic, the mixture of the preferred sorbitol of excipient and lactose, the preferred sodium sulfite of antioxidant, the preferred chlorobutanol of local analgesia agent, buffer agent preferably phosphoric acid sodium dihydrogen, the preferred 6.0-7.0 of pH value.
The present invention also provides preparation to contain the injection medicine method for compositions of Thymosin alpha 1, and this method may further comprise the steps:
(1) pharmaceutic adjuvant is dissolved in the water for injection, fully dissolving;
(2) in the middle aqueous solution that obtains of step (1), add Thymosin alpha 1, and it is fully dissolved;
(3) in the middle aqueous solution that obtains of step (2), add the pH regulator agent, be adjusted to required pH value;
(4) filter the also solution of lyophilization step (3) preparation.
Beneficial effect of the present invention: stability significantly increases, and is beneficial to circulation and the use of medicine, and accepts extensively for the patient.
The specific embodiment:
The present invention has carried out lot of experiments for the amount of investigating excipient, pH value, the buffer salt radical ion stability influence to injection Thymosin alpha 1 injection medicine compositions.Verified, to fill sugar composite for two kinds and be better than a kind of filling sugar, concrete outcome is as follows: sorbitol+lactose＞sorbitol+mannitol＞sorbitol+sucrose＞sorbitol＞mannitol＞sucrose.Simultaneously, the pH value scope of preparation has also been done big quantity research, the result shows that best pH scope is 6.0-7.5.
Be described in detail below in conjunction with the embodiment of the present invention of embodiment, but it will be understood to those of skill in the art that the following example only is used for explanation the present invention, and should not be considered as limiting scope of the present invention.
Embodiment 1
Embodiment 1 Thymosin alpha 1 injection medicine composite formula is: the 1.6mg/ml Thymosin alpha 1, and the 4mg/ml sorbitol, the 4mg/ml lactose, the 10mg/ml sodium sulfite, the 8mg/ml chlorobutanol, the 20mM sodium dihydrogen phosphate, it is 6.5 that acetic acid is regulated pH.
Its preparation process is as follows: add the 4g sorbitol in the 1000ml beaker, the 4g lactose, the 10g sodium sulfite, the 8g chlorobutanol adds water for injection and fully dissolves, and adds Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding sodium dihydrogen phosphate to its concentration is 20mM, and with 1NHCl with pH regulator to 6.5, add injection water standardize solution.Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered.Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration.Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
Make 1000 in injection Thymosin alpha 1 preparation by embodiment 1, by accelerated test its stability is investigated.By animal blood vessels zest, muscle irritation and anaphylaxis experiment, local irritation is investigated.By with the common infusion fluid compatibility, observe its outward appearance, related substance and changes of contents and investigated its stability in common infusion fluid.
Accelerated test:
Listing reference substance and the contrast of embodiment 1 sample
Respectively the batch sample of commercially available injection Thymosin alpha 1 preparation reference substance and embodiment one being put into temperature and be 40 ± 2 ℃, relative humidity and be 75% ± 5% climatic chamber investigates, 0,1,2,3 and sampling and measuring 6 months the time, the results are shown in Table 1-1 and table 1-2 respectively.
The commercially available reference substance accelerated test of table 1-1 result
Table 1-2 embodiment 1 sample accelerated test result
By showing 1-1 and table 1-2 as can be seen, investigate 6 months through accelerated test, the injection Thymosin alpha 1 preparation of embodiment 1 preparation compares with the injection Thymosin alpha 1 preparation that has gone on the market, appearance luster, pH, clarity of solution index are suitable, the impurity of the test sample of listing increases, content descends obviously, show that the Thymosin alpha 1 injection that the present invention prepares can preserve under room temperature, stability increases.
Blood vessel irritation, muscle irritation, anaphylaxis and hemolytic experiment:
Blood vessel irritation:
Choose 6 of the undamaged healthy rabbits of ears, left side auricular vein injection embodiment 1 injection 1ml, capacity 5% glucose injections such as auris dextra injection, were injected 7 days continuously at every day 1 time.
During the injection, regularly observe the irritative response of auricular vein every day.Put to death rabbit on the 8th day, and got bilateral auricular vein and surrounding tissue, use formaldehyde fixed, do the conventional organization section at the injection site proximal part, observation has or not pathological change under the light microscopic.
The result shows that the zest of rabbit auricular vein injection embodiment 1 injection compares no significant difference with 5% glucose injection.Inflammatory reactions such as the congestion of blood vessel, surrounding tissue edema are not seen in perusal.Tissue slice checks, do not see that blood vessel structure is unusual, endothelial injury, thrombosis and other pathological change, shows the injection Thymosin alpha 1 pharmaceutical composition nonirritant of embodiment 1 preparation.
Muscle irritation:
Get 6 of healthy rabbits, injection embodiment 1 injection 1ml in every rabbit left side quadriceps femoris, inject with the volume normal saline on the right side.The injection back is observed injection site muscle and is had or not reactions such as hyperemia, edema, and (the 3rd day) sacrificed by exsanguination behind the half animal 48h is vertically cut skin, and injection site, perusal both sides has or not reactions such as hyperemia, edema, and gets its tissue and do pathologic finding.Remaining animal continues to observe 14d, repeats aforesaid operations in the 18th day after the sacrificed by exsanguination, estimates the irritant reaction of this medicine then.
The result shows, after injecting embodiment 1 injection in the quadriceps femoris of rabbit left side, perusal injection site muscle does not have reactions such as hyperemia, edema, and explicitly irritant reaction such as tissue degeneratiaon or necrosis are not also seen in the pathological tissue inspection, compare no significant difference with the normal saline side.
Sensitization to Cavia porcellus:
Choose 6 of healthy guinea pigs, every lumbar injection embodiment 1 injection 0.5ml, the next day, inject 1 time, injects altogether 3 times.Be divided into 2 groups then at random, after the 1st administration 14 or 21 days respectively, intravenous injection embodiment 1 injection 1ml.Observe Cavia porcellus and have or not allergic symptoms such as excited uneasiness, dyspnea.
Two groups of Cavia porcelluss of result are all movable normal, do not see adnormal respiration etc.
Blood vessel irritation, muscle irritation and anaphylaxis experiment show that embodiment 1 injection does not have tangible zest, anaphylaxis.
Stability experiment in the transfusion:
Injection Thymosin alpha 1 with 10ml purified water dilution embodiment 1 preparation, draw 10ml respectively, use common infusion fluid respectively: 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS), be diluted to 200ml, making Thymosin alpha 1 concentration is 0.008mg/ml.Respectively at 25 ℃, minute is observed its outward appearance, impurity, changes of contents, the results are shown in Table 1-3.
Table 1-3 injection stability experiment
The result shows, Thymosin alpha 1 preparation and the common infusion fluid of embodiment 1 preparation, 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS) compatibility use, and stability is all better, therefore, this embodiment makes sample and can use with these compatibilities of infusing.
Embodiment 2-embodiment 10
Embodiment 2-embodiment 10 prescriptions are as following table
Embodiment 1 Thymosin alpha 1 injection medicine composite formula is: the 1.6mg/ml Thymosin alpha 1, and the 4mg/ml sorbitol, the 4mg/ml lactose, the 10mg/ml sodium sulfite, the 8mg/ml chlorobutanol, the 20mM sodium dihydrogen phosphate, it is 6.5 that acetic acid is regulated pH.Sorbitol+lactose＞sorbitol+mannitol＞sorbitol+sucrose＞sorbitol＞mannitol＞sucrose.
The preparation process of embodiment 2-embodiment 10 and embodiment's 1 is basic identical, all be in the 1000ml beaker, to add all pharmaceutic adjuvants earlier, adding water for injection fully dissolves, adding Thymosin alpha 1 to its final standardize solution concentration is 1.6mg/ml, add buffer salt to its concentration, and with pH regulator to 6.5, add injection water standardize solution with 1NHCl.Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered.Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration.Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
Make 1000 in injection Thymosin alpha 1 preparation by embodiment 2-embodiment 10, by accelerated test its stability is investigated.By animal blood vessels zest, muscle irritation and anaphylaxis experiment, local irritation is investigated.By with the common infusion fluid compatibility, observe its outward appearance, related substance and changes of contents and investigated its stability in common infusion fluid.
Accelerated test:
Method by embodiment 1 is carried out accelerated test to embodiment 2-embodiment 10 gained preparation compositions respectively, the results are shown in Table 2-1-10-1.
Table 2-1 sample accelerated test result
Table 3-1 sample accelerated test result
Table 4-1 sample accelerated test result
Table 5-1 sample accelerated test result
Table 6-1 sample accelerated test result
Table 7-1 sample accelerated test result
Table 8-1 sample accelerated test result
Table 9-1 sample accelerated test result
Table 10-1 sample accelerated test result
Contrast as can be seen by table 1-1 and table 2-3-table 10-3, investigate 6 months through accelerated test, the injection Thymosin alpha 1 preparation of embodiment 2-embodiment 10 preparations compares with the injection Thymosin alpha 1 preparation that has gone on the market, appearance luster, pH, clarity of solution index are suitable, the impurity of the test sample of listing increases, content descends obviously, show that the Thymosin alpha 1 injection that the present invention prepares can preserve under room temperature, stability increases.
Blood vessel irritation, muscle irritation, anaphylaxis and hemolytic experiment:
Blood vessel irritation:
Adopt the method identical with embodiment 1, the result shows that the zest of rabbit auricular vein injection embodiment 2-embodiment 10 injection is with 5% glucose injection comparison no significant difference.Inflammatory reactions such as the congestion of blood vessel, surrounding tissue edema are not seen in perusal.Tissue slice checks, do not see that blood vessel structure is unusual, endothelial injury, thrombosis and other pathological change.The injection Thymosin alpha 1 pharmaceutical composition nonirritant that shows embodiment 2-embodiment 10 preparations.
Muscle irritation:
Adopt the method identical with embodiment 1, the result shows, after injecting real embodiment 2-embodiment 10 injection in the quadriceps femoris of rabbit left side, perusal injection site muscle does not have reactions such as hyperemia, edema, explicitly irritant reaction such as tissue degeneratiaon or necrosis are not also seen in the pathological tissue inspection, compare no significant difference with the normal saline side.
Sensitization to Cavia porcellus:
Adopt the method identical with embodiment 1, the result shows that behind intravenous injection embodiment 2-embodiment 10 injection, two groups of Cavia porcelluss of result are all normally movable, do not see adnormal respiration etc.
Blood vessel irritation, muscle irritation, external hemolytic and anaphylaxis experiment show that embodiment 2-embodiment 10 injection do not have tangible zest, anaphylaxis.
Stability experiment in the transfusion:
Stability experiment in respectively embodiment 2-embodiment 10 gained preparation compositions being infused by the method for embodiment 1 the results are shown in Table 2-4-10-4.
Table 2-4 injection stability experiment
Table 3-4 injection stability experiment
Table 4-4 injection stability experiment
Table 5-4 injection stability experiment
Table 6-4 injection stability experiment
Table 7-4 injection stability experiment
Table 8-4 injection stability experiment
Table 9-4 injection stability experiment
Table 10-4 injection stability experiment
The above results shows, Thymosin alpha 1 preparation and the common infusion fluid of embodiment 2-embodiment 10 preparations, 0.9% sodium chloride injection (0.9%NS), 5% glucose injection (5%GS) compatibility use, and stability is all better, therefore, this embodiment makes sample and can use with these compatibilities of infusing.
Embodiment 1-embodiment 10 shows that also its medicinal effects is more desirable than the commercial preparation after adding antioxidant and local analgesic, and the sense of discomfort when having alleviated patient infusion is more conducive to the patient and accepts extensively.
Claims (10)
1. a more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, the 4mg/ml sorbitol, the 4mg/ml lactose, 10mg/ml sodium sulfite, 8mg/ml chlorobutanol, the 20mM sodium dihydrogen phosphate, it is 6.5 that acetic acid is regulated pH; Preparation technology is: add the 4g sorbitol in the 1000ml beaker, the 4g lactose, the 10g sodium sulfite, the 8g chlorobutanol adds water for injection and fully dissolves, and adds Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding sodium dihydrogen phosphate to its concentration is 20mM, and with 1N acetic acid with pH regulator to 6.5, add and inject the water standardize solution; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
2. a more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, the 4mg/ml sorbitol, 4mg/ml mannitol, 10mg/ml sodium sulfite, 8mg/ml chlorobutanol, the 20mM sodium citrate, it is 6.5 that acetic acid is regulated pH; Preparation technology is: add the 4g sorbitol in the 1000ml beaker, 4g mannitol, the 10g sodium sulfite, the 8g chlorobutanol adds water for injection and fully dissolves, and adds Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding sodium citrate to its concentration is 20mM, and with 1N acetic acid with pH regulator to 6.5, add and inject the water standardize solution; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
3. a more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, the 4mg/ml sorbitol, 4mg/ml sucrose, 10mg/ml sodium sulfite, 8mg/ml chlorobutanol, the 20mM sodium dihydrogen phosphate, it is 6.5 that acetic acid is regulated pH; Preparation technology is: add the 4g sorbitol in the 1000ml beaker, 4g sucrose, the 10g sodium sulfite, the 8g chlorobutanol adds water for injection and fully dissolves, and adds Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding sodium dihydrogen phosphate to its concentration is 20mM, and with 1N acetic acid with pH regulator to 6.5, add and inject the water standardize solution; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
4. more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, and the 8mg/ml sorbitol, the 10mg/ml sodium sulfite, the 8mg/ml benzyl alcohol, the 20mM disodium-hydrogen, it is 6.5 that acetic acid is regulated pH; Preparation technology is: add the 8g sorbitol in the 1000ml beaker, the 10g sodium sulfite, the 8g benzyl alcohol, adding water for injection fully dissolves, add Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding disodium-hydrogen to its concentration is 20mM, and with pH regulator to 6.5, add injection water standardize solution with 1N acetic acid; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
5. more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, and 8mg/ml mannitol, the 10mg/ml sodium acetate, the 8mg/ml chlorobutanol, the 20mM disodium-hydrogen, it is 6.5 that acetic acid is regulated PH; Preparation technology is: add 8g mannitol in the 1000ml beaker, the 10g sodium acetate, the 8g chlorobutanol, adding water for injection fully dissolves, add Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding disodium-hydrogen to its concentration is 20mM, and with pH regulator to 6.5, add injection water standardize solution with 1N acetic acid; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
6. more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, and 8mg/ml sucrose, 8mg/ml sulphuric acid one hydrogen sodium, the 8mg/ml benzyl alcohol, the 20mM sodium dihydrogen phosphate, it is 6.5 that acetic acid is regulated pH; Preparation technology is: add 8g sucrose in the 1000ml beaker, 8g sulphuric acid one hydrogen sodium, the 8g benzyl alcohol, adding water for injection fully dissolves, add Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding sodium dihydrogen phosphate to its concentration is 20mM, and with pH regulator to 6.5, add injection water standardize solution with 1N acetic acid; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
7. more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, and the 5mg/ml sorbitol, the 5mg/ml lactose, 8mg/ml sodium thiosulfate, the 8mg/ml procaine hydrochloride, it is 6.5 that acetic acid is regulated pH; Preparation technology is: add the 5g sorbitol in the 1000ml beaker, the 5g lactose, 8g sodium thiosulfate, the 8g procaine hydrochloride, add water for injection and fully dissolve, add Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, and with pH regulator to 6.5, add injection water standardize solution with 1N acetic acid; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
8. more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, and the 15mg/ml sorbitol, 8mg/ml dibutyl phenol, the 8mg/ml benzyl alcohol, the 20mM sodium dihydrogen phosphate, it is 6.6 that hydrochloric acid is regulated pH; Preparation technology is: add the 15g sorbitol in the 1000ml beaker, 8g dibutyl phenol, the 8g benzyl alcohol, adding water for injection fully dissolves, add Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding sodium dihydrogen phosphate to its concentration is 20mM, and with pH regulator to 6.6, add injection water standardize solution with 1NHC1; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
9. more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, and the 8mg/ml sorbitol, the 8mg/ml sodium pyrosulfite, the 8mg/ml chlorobutanol, the 20mM sodium citrate, it is 6.5 that acetic acid is regulated pH; Preparation technology is: add the 8g sorbitol in the 1000ml beaker, the 8g sodium pyrosulfite, the 8g chlorobutanol, adding water for injection fully dissolves, add Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding sodium citrate to its concentration is 20mM, and with pH regulator to 6.5, add injection water standardize solution with IN acetic acid; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/m1 injection Thymosin alpha 1 preparation.
10. a more stable Thymosin alpha 1 injection medicine compositions is characterized in that: contain the 1.6mg/ml Thymosin alpha 1, the 4mg/ml lactose, 4mg/ml mannitol, 8mg/ml sodium thiosulfate, 8mg/ml benzyl alcohol, the 20mM sodium dihydrogen phosphate, it is 7.0 that acetic acid is regulated pH; Preparation technology is: add the 4g lactose in the 1000ml beaker, 4g mannitol, 8g sodium thiosulfate, the 8g benzyl alcohol adds water for injection and fully dissolves, and adds Thymosin alpha 1, to its final standardize solution concentration be 1.6mg/ml, adding sodium dihydrogen phosphate to its concentration is 20mM, and with 1N acetic acid with pH regulator to 7.0, add and inject the water standardize solution; Before filtration, add the 12.5g activated carbon in the injection, under agitation adsorbed pyrogen 30 minutes, decarburization is filtered; Filtrate is filtered through 0.22 μ m titanium rod filter, again through 0.22 μ m microporous filter membrane aseptic filtration; Be sub-packed in the 10ml vial, lyophilization, tamponade, Zha Gai, obtaining concentration is 1.6mg/ml injection Thymosin alpha 1 preparation.
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| CN1840177A (en) * | 2006-01-11 | 2006-10-04 | 成都圣诺科技发展有限公司 | Injection liquid of thymic peptide alpha 1 and preparation method thereof |
| CN101020048A (en) * | 2007-02-12 | 2007-08-22 | 广东天普生化医药股份有限公司 | Pyemia treating medicine composition |
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