CN104352459B - Somatostatin freeze-dried powder - Google Patents
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- CN104352459B CN104352459B CN201410747747.3A CN201410747747A CN104352459B CN 104352459 B CN104352459 B CN 104352459B CN 201410747747 A CN201410747747 A CN 201410747747A CN 104352459 B CN104352459 B CN 104352459B
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Abstract
The somatostatin freeze-dried powder that the present invention provides; belong to field of biological pharmacy; somatostatin freeze-dried powder is made up of somatostatin, mannitol, the tert-butyl alcohol, PH regulator, and the method that the present invention provides is first to be dissolved in water for injection by mannitol, adds the tert-butyl alcohol and somatostatin; benefit adds to the full amount of water for injection; after regulating suitable pH value, fill is in ampoule, after lyophilization; ampoule is drawn and seals and get final product, make up a prescription and freezing dry process is filled with noble gas and protects.It is low that somatostatin lyophilized injectable powder prepared by the present invention has moisture, and outward appearance is good, has related substance low, it is adaptable to the advantages such as long term storage.
Description
Technical field
The invention belongs to field of biological pharmacy, be specifically related to a kind of injection somatostatin freeze-dried powder
Background technology
Somatostatin (somatostatin) is a kind of somatostatin (SRLF, the GH-of D emiocytosis
RIF), being present in gastrointestinal tract and central nervous system, wherein digestive tract is maximum containing total amount, but Cmax sees hypothalamus, can
Suppress secretion and the gastrointestinal peristalsis of multiple gastrointestinal hormone.Somatostatin swashs as a kind of many peptides with different physiological roles
Element, people are the most successfully developed into human drugs, and its indication includes: (1) serious acute Esophageal varix bleeding；
(2) serious acute stomach or duodenal ulcer and hemorrhage, or complicated with acute erosive gastritis or hemorrhagic gastritis；(3) pancreatic surgery
The prevention of post-operative complication and treatment；(4) the auxiliary treatment of pancreas, gallbladder and intestinal fistula；(5) auxiliary of diabetic ketoacidosis is controlled
Treat.
Additionally existing many document report somatostatin can treat digestive tract hemorrhage, esophageal varicosis crushes and splits
Blood, acute pancreatitis, hepatocarcinoma and neuroendocrine tumor such as pancreatic islet tumor, owing to somatostatin biological action is various, therefore
There is application prospect widely.
Somatostatin is the tetradecapeptide of synthetic, the peptide bond less stable in its strand, compares easy fracture, especially
It is the most more easy fracture, is cracked into little peptide, affect the quality of product, be prepared into water-free freeze-dried powder dosage form
Can effectively solve the problem that this problem.
Chinese patent CN11415378A discloses a kind of somatostatin freeze-dried powder and preparation technology thereof, and somatostatin freezes
Dry powder pin is made up of following component: somatostatin: 250mg or 3000mg, excipient: 5000～20000mg, pH adjusting agent: 0～
100ml, water for injection extremely: 600ml.Its preparation technology comprises the steps: that excipient is placed in the beaker of sterilizing by (1)
In, add water for injection, after stirring and dissolving, addition 0.1～0.3% needle-use activated carbon, stir 20～80 points at 20～60 DEG C
Clock；(2) somatostatin addition is taken off in charcoal with 0.6 sterilized μm filter membrane, be sufficiently stirred for making dissolving, molten with the regulation of PH regulator
Liquid pH value, to 4.0～6.0, injects water to 600ml scale, degerming with 0.22 μm membrane filtration；(3) by every bottle of 0.6ml's
Loading amount is sub-packed in glass glass tube vial, sends into freezer dryer lyophilizing, adds a cover, label and get final product.
Chinese patent CN1559396A discloses a kind of injection somatostatin preparation and preparation technology thereof, and this technology uses
Hyperfiltration technique produces injection somatostatin preparation, is drawn by micro activated carbon particle after can avoiding using activated carbon adsorption in prior art
Enter and preparation causes the injury to human body, improve preparation purity, the stability of effective ingredient, finished product in preparation can be ensured simultaneously
Dissolubility, easy-formation, but hyperfiltration technique require technical sophistication, the production cost of product is higher.
Chinese patent CN103222963A discloses somatostatin lyophilized injectable powder, and this invention relates to a kind of freeze-dried powder
Agent, wherein comprises somatostatin and mannitol, the material wherein comprised in terms of the somatostatin of every 0.75 weight portion, mannitol
Amount is 5～200 weight portions.Its preparation technology comprises the steps: that (a) weighs the somatostatin of recipe quantity and optional manna
Alcohol, optional maltose alcohol, add appropriate water for injection, make dissolving, adds activated carbon, stirring, filtering decarbonization；B () is added
Water for injection is 0.1～20mg to the somatostatin amount contained in every 1ml solution, stirs, and measures solution ph and optionally
Mensuration active component content, if desired with acid-base modifier regulate to 4.5～6.5, such as to 5.0～6.0；C () is by medicinal liquid
Aseptic filtration, fill is in vial；D () lyophilization removes moisture, seal, to obtain final product.
Chinese patent CN103417499A discloses the preparation method of a kind of somatostatin freeze-dried powder, the method include with
Lower step: mannitol and somatostatin are dissolved in water for injection and prepare mannitol and somatostatin mixed solution, described mixing by (1)
In solution, the concentration of mannitol is 2g/100ml, and the concentration of somatostatin is 0.05～0.6g/100ml；(2) by mannitol and life
Long chalone mixed solution pH adjusting agent regulation pH value is to 4.5～5.0；(3) by the solution filter of 0.22 μm after regulation pH value
Film or filter element filtering；(4) solution after filtering carries out fill and partly jumps a queue, lyophilization, and total head plug under vacuum state rolls lid,
Obtain.
By the research of above somatostatin freeze-dried powder is found, somatostatin freeze-dried powder prepared by said method
Moisture is relatively big, and finds its moisture during depositing and have related substance to be continuously increased, and the clarity after redissolution is bad
Phenomenon.
Summary of the invention
The invention aims to overcome the deficiencies in the prior art, it is provided that a kind of somatostatin freeze-dried powder, making up a prescription
During add the appropriate tert-butyl alcohol, and fill is in ampoule bottle, and the somatostatin freeze-dried powder moisture of gained is relatively low, warp
Crossing long term test and find the somatostatin freeze-dried powder containing the tert-butyl alcohol, moisture increases inconspicuous, and redissolves effective,
Related substance and content is had to be better than the pertinent regulations of Chinese Pharmacopoeia version in 2010 second, it is adaptable to long term storage.
Somatostatin freeze-dried powder of the present invention, formula composition is as follows:
The formula of the present invention obtains through substantial amounts of experiment screening repeatedly, is preparing somatostatin freeze-dried powder process
Middle inventor is found surprisingly that, after adding the tert-butyl alcohol of recipe quantity, in addition to dissolving somatostatin, additionally it is possible to accelerate raw
The dissolving of long chalone freeze-dried powder, increases the stability of principal agent, and the moisture that especially can reduce in somatostatin lyophilized powder contains
Amount, is embodied in after long-time stability investigate experiment, and in sample, moisture is stable, and impurity content change is less,
Lyophilized formulations stability is improved, and preparation process is simple, and cost is relatively low, is suitable for large-scale production.Preferably, with weight
Than meter, somatostatin: the tert-butyl alcohol=1:16.
Described somatostatin freeze-dried powder, calculates, somatostatin by quality ratio: mannitol=1:10～100, is preferably
Somatostatin: mannitol=1:20～50, more preferably somatostatin: mannitol=1:30.Preferably ratio is inventor's warp
Crossing what repetition test obtained, find in experimentation, when content one timing of principal agent, with mass ratio range, mannitol presses down with growth
When the ratio of element is 5:1, product appearance character is bad, long-term placement product atrophy, has related substance to increase；But mannitol and life
When the ratio of long chalone is 120:1, owing to mannitol content is big, when lyophilizing solidifies, center is squeezed and the hard of projection occurs
Lid, thus cause lyophilizing thorough, the moisture entrapment contained, cause related substance to increase, cause redissolution effect bad, the sweetest
Dew alcohol is non-active ingredient, and consumption is excessive, brings certain side effect to human body, brings certain safety hidden to clinical application
Suffering from, the preferred ratio of the present inventor both can guarantee that the safety of product, can guarantee that again the high-quality of product, when mannitol and growth
The ratio of chalone is 10～100:1, and especially mannitol is ratio during 30:1 with the ratio of somatostatin, containing of freeze-dried powder
The water yield is less than other ratios, and long-term placement process moisture is advanced the speed the slowest, and effect of redissolving is preferable.
Described pH adjusting agent can be glacial acetic acid, citric acid, lactic acid, hydrochloric acid or glycine, and the present invention is preferably ice
Acetic acid, more preferably 1mol/L glacial acetic acid.
Another object of the present invention is to provide the preparation method of a kind of somatostatin freeze-dried powder, specifically comprise the following steps that
(1) weigh the mannitol of recipe quantity, add a certain amount of water for injection, stirring and dissolving, add the tertiary fourth of recipe quantity
Alcohol, stirring and dissolving, add the somatostatin of recipe quantity, stirring makes principal agent be completely dissolved；
(2) add the activated carbon of recipe quantity, stir 15～30 minutes, de-charcoal；
(3) mending and add to the full amount of water for injection, use PH regulator regulation pH value to 4.0～6.0, the process of making up a prescription carries out filling lazy
Property gas shield；
(4) fill: by liquid medicine filling in ampoule bottle, lyophilizing；
(5) freeze-drying curve: after the goods inlet that fill obtains, is cooled to-35 ± 5 DEG C of pre-freezes, keeps 1～3 hour；Heat up
To-15 ± 5 DEG C, it is incubated 2～3 hours, then is cooled to-35 ± 5 DEG C of insulations 1～3 hour；Open cold-trap, open vacuum；By baffle temperature
It is warming up to-15～-10 DEG C, then keeps 5～10 hours；Baffle temperature is warming up to-5～5 DEG C, then keeps 3～5 hours；
Again baffle temperature is warming up to 25～40 DEG C, then keeps 3～5 hours.After lyophilizing terminates, under vacuum state, it is filled with indifferent gas
Body, takes the dish out of the pot；
(6) drawing envelope: drawn by the ampoule after lyophilizing and seal and get final product, ambient humidity is relative humidity 15%～40%, draws seal ring border
Temperature controls at 15 DEG C～20 DEG C.
The present invention is in somatostatin freeze-dried powder preparation process, and the noble gas being filled with can be nitrogen, argon, dioxy
Change carbon one therein, most preferably nitrogen.
Inventor finds in preparation process, and varying environment has the biggest difference to the moisture of somatostatin lyophilized powder
Different, strict ambient temperature and humid control can prevent the somatostatin lyophilized powder moisture absorption, it is ensured that the moisture of freeze-dried powder is closed
Lattice and stability, be filled with the noble gases such as nitrogen in the process of making up a prescription and freeze-drying process, can limit in environment to a certain extent
Oxygen and moisture enter product, avoid somatostatin to contact with extraneous to greatest extent, and moisture reduces；The present invention is last
Pouring process in select ampoule bottle as container, it is to avoid use other water translocations caused with plug container, it is ensured that
Product is after long-time placement, and moisture remains at relatively low level.
The qualified samples of embodiment and comparative example is placed 24 months for a long time, experimental condition (2～8 DEG C, relative humidity 60% ±
10%) in sampling in the 0th, 6,12,18,24 months, according to 2010 editions " Chinese Pharmacopoeia " second crude drug and pharmaceutical preparation stability
Test direction principle detects, and long-term test results is shown in Table 1, the embodiment moisture of 1～5 the 24th months is 1.75%,
1.74%, 1.58%, 1.73%, 1.76%, moisture adds 0.34%, 0.36%, 0.27%, 0.37%, 0.34% respectively,
And the equal clear, colorless of embodiment group solution after the long term test of 24 months, it is seen that foreign body and have related substance to meet 2010
The regulation of version Chinese Pharmacopoeia；And comparative example 1～6 24th month moisture be 2.69%, 2.15%, 2.16%, 2.59%,
2.68%, 2.47%, 2.61%, moisture adds 0.76% respectively, 0.56%, 0.60%, 0.64%, 0.68%, 0.66%,
0.71%, and comparative example 1～6 solution when 24th month is the most muddy, it is seen that and foreign body is defective, and particularly comparative example 1 is the 6th
When individual month, solution starts turbid phenomenon occur, and above result of the test shows, somatostatin lyophilized injectable powder prepared by embodiment group
Stability is high during storage, and product moisture is low, and outward appearance is good, has related substance low, is conducive to transport visible foreign matters symbol for a long time
Close pharmacopoeial requirements.Its quality of the product that the present invention prepares is substantially better than comparative example group.
Detailed description of the invention
Further illustrate the present invention by the following examples, but these embodiments limit the present invention never in any form.
Embodiment 1
Prescription:
Specifically comprise the following steps that
(1) weigh the mannitol of 6.0g, add 10 DEG C of waters for injection of 320ml, stirring and dissolving, add the tertiary fourth of 4.8g
Alcohol, stirring and dissolving, add the somatostatin of 0.6g, stirring is completely dissolved；
(2) add the activated carbon of 0.12g, stir 20 minutes, filtering decarbonization；
(3) benefit injects water to 400ml, and with 1mol/L glacial acetic acid regulation pH value to 5, the process of making up a prescription carries out inflated with nitrogen guarantor
Protect；
(3) fill: by liquid medicine filling in ampoule bottle, lyophilizing；
(4) freeze-drying curve: after the goods inlet that fill obtains, is cooled to-35 DEG C of pre-freezes, keeps 3 hours；It is warming up to-5
DEG C, it is incubated 2 hours, then is cooled to-20 DEG C of insulations 3 hours；Open cold-trap, open vacuum；Baffle temperature is warming up to-12 DEG C, keeps 8
Hour；Baffle temperature is warming up to 0 DEG C, keeps 4 hours；Again baffle temperature is warming up to 35 DEG C, keeps 3 hours；Lyophilizing terminates
After, inflated with nitrogen under vacuum state, tamponade, take the dish out of the pot；
(5) drawing envelope: drawn by the ampoule after lyophilizing and seal and get final product, ambient humidity is relative humidity 25%.
Embodiment 2
Prescription:
Preparation technology is in addition to adjuvant and consumption difference, and other are substantially the same manner as Example 1.
Embodiment 3
Prescription:
Preparation technology is in addition to adjuvant and consumption difference, and other are substantially the same manner as Example 1.
Embodiment 5
Prescription:
Preparation technology is in addition to adjuvant and consumption difference, and other are substantially the same manner as Example 1.
Comparative example 1
Prescription:
Specifically comprise the following steps that
(1) weighing the lactose of 18.0g, add the water for injection 20 DEG C of 320ml, stirring and dissolving, the growth adding 0.6g presses down
Element, stirring makes principal agent be completely dissolved；
(2) add the activated carbon of 0.30g, stir 15 minutes, de-charcoal；
(3) benefit injects water to 400ml, is 5.0 with 1mol/L glacial acetic acid pH value；
(3) fill: by liquid medicine filling in cillin bottle, lyophilizing；
(4) freeze-drying curve: after the goods inlet that fill obtains, is cooled to-35 DEG C of pre-freezes, keeps 3 hours；It is warming up to-5
DEG C, it is incubated 2 hours, then is cooled to-20 DEG C of insulations 3 hours；Open cold-trap, open vacuum；Baffle temperature is warming up to-12 DEG C, keeps 8
Hour；Baffle temperature is warming up to 0 DEG C, keeps 4 hours；Again baffle temperature is warming up to 35 DEG C, keeps 3 hours；Lyophilizing terminates
After, inflated with nitrogen under vacuum state, tamponade, take the dish out of the pot.
Comparative example 2
Prescription:
Preparation technology is in addition to raw material and consumption difference, and other is substantially the same manner as Example 1.
Comparative example 3
Prescription:
Preparation technology is in addition to raw material and consumption difference, and other is substantially the same manner as Example 1.
Comparative example 4
Prescription:
Preparation technology is in addition to raw material and consumption difference, and other is substantially the same manner as Example 1.
Comparative example 5
Prescription:
Concrete operation step is as follows:
(1) mannitol is placed in the beaker of sterilizing, adds water for injection, after stirring and dissolving, add 0.30g pin and use
Activated carbon, stirs 80 minutes at 60 DEG C；
(2) somatostatin addition is taken off in charcoal with 0.6 sterilized μm filter membrane, be sufficiently stirred for making dissolving, adjust with glacial acetic acid
Joint solution ph, to 5.0, injects water to 600ml scale, degerming with 0.22 μm membrane filtration；
(3) it is sub-packed in glass glass tube vial by the loading amount of every bottle of 0.6ml；
(4) lyophilizing: pre-freeze (5h, room temperature is cooled to-40 DEG C), is incubated (1h ,-35 DEG C), evacuation (0.5h ,-40 DEG C), heats up
(9 DEG C/h, be warming up to-5 DEG C, 5h, then are heated up with 7 DEG C/h, each temperature retention time 4h), insulation (25 DEG C of insulation 3h), quality inspection
Qualified add a cover, label and get final product.
Comparative example 6
Prescription:
Concrete operation step is as follows:
(1) mannitol and somatostatin are dissolved in water for injection and prepare mannitol and somatostatin mixed solution, described mixed
Closing the concentration of mannitol in solution is 2g/100ml, and the concentration of somatostatin is 0.4g/100ml；
(2) use breast acid for adjusting pH value to 4.5 in mannitol and somatostatin mixed solution；
(3) by the solution filter membrane of 0.22 μm or the filter element filtering after regulation pH value；
(4) solution after filtering carries out fill and partly jumps a queue, lyophilization, including pre-freeze: the solution after filtering is placed in-
30 DEG C are incubated 4 hours；Once distillation: in vacuum less than 10Pa, baffle temperature distils 15 hours under the conditions of being-10 DEG C；Do again
Dry: in vacuum less than 10Pa, baffle temperature is 25 DEG C and is dried 3 hours again.
Comparative example 7
Prescription:
Concrete operation step is as follows:
(1) somatostatin and the mannitol that weigh recipe quantity add appropriate water for injection, make dissolving, add activated carbon,
Stirring, filtering decarbonization；
(2) mending the somatostatin amount injecting water to contain in every 1ml solution is 2.0mg, stirs, adjusts with hydrochloric acid
Joint pH to 6.0；
(3) by medicinal liquid aseptic filtration, fill is in vial；
(4) lyophilization removes moisture, seals, to obtain final product.
Checking embodiment
Detect with pharmaceutical preparation stability test guideline according to 2010 editions " Chinese Pharmacopoeia " second crude drug,
Long term test such as table 1:
[assay] measures according to high performance liquid chromatography (annex VD):
Chromatographic condition and system suitability test: be filler with octadecylsilane chemically bonded silica；(take with phosphoric acid solution
Phosphatase 11 1ml, add water 800ml, with triethylamine adjust pH value to 2.3, be diluted with water to 1000ml)～acetonitrile (75:25) for flowing
Phase；Flow velocity is 1.5ml per minute；Detection wavelength is 215nm；Number of theoretical plate is calculated by somatostatin peak should be not less than 1500；
Algoscopy: take this product 5 bottles, adds water appropriate respectively, make contents melting and quantitatively dilution make in every 1ml containing about
The solution of 0.1mg, 5 bottles of full doses mix and shake up, as need testing solution；Precision measures 20 μ l and injects chromatograph of liquid, record
Chromatogram；Separately take somatostatin reference substance and make in every 1ml the solution containing about 0.1mg in right amount, be measured in the same method, by external standard method with peak
Areal calculation, to obtain final product；Crude drug also can measure similarly.
[having related substance] measures according to high performance liquid chromatography (annex VD):
Take this product content, be dissolved in water and make the solution containing 0.5mg in every 1ml, as need testing solution；Accurate amount
Take 2ml, put in 100ml measuring bottle, be diluted with water to scale and shake up, as contrast solution；Use octadecylsilane chemically bonded silica
For filler, with phosphoric acid solution, (taking phosphatase 11 1ml, add water 800ml, adjusts pH value to 2.3 with triethylamine, is diluted with water to
1000ml) it is mobile phase A；Acetonitrile is Mobile phase B；Flow velocity is 1.5ml per minute；Detection wavelength is 215nm；According to the form below carries out ladder
Degree eluting；Number of theoretical plate is calculated by somatostatin peak should be not less than 1500；
Take contrast solution 50 μ l and inject chromatograph of liquid, regulate detection sensitivity, make main constituent chromatograph peak height be about full amount
The 20% of journey；Precision measures need testing solution and each 50 μ l of contrast solution, is injected separately into chromatograph of liquid, records chromatogram.
If any impurity peaks in the chromatogram of need testing solution, in addition to solvent peak, single impurity peak area cannot be greater than comparison
The half (1.0%) of solution main peak area；Each impurity peak area and cannot be greater than contrast solution main peak area (2.0%).
Table 1 embodiment, the long-term shelf-stability of comparative example investigate result
By above-mentioned table 1 it can be seen that keep stable through the freeze-dried powder moisture of long term test embodiment 1～5, water
Point content increases inconspicuous, redissolve effect, have related substance and visible foreign matters to be superior to pharmacopoeial requirements；Comparative example 1 uses lactose to make
For excipient, moisture increases substantially, and when 6 months, the solution of freeze-dried powder began to muddiness；Comparative example 2, comparative example 3 and
Comparative example 4 somatostatin is 1:5,1:120 and 1:200 with the ratio of mannitol respectively, contains through 24 months long term test moisture
Quantitative change is 2.15%, 2.16%, 2.59%, it is seen that foreign body is defective；The moisture in each month of comparative example 5～7 and increasing
Rate of acceleration is significantly greater than embodiment each month moisture, and when 6 months, the solution of freeze-dried powder began to muddiness, was unsuitable for
Long term storage.
Claims (7)
1. a somatostatin freeze-dried powder, with mass ratio range, is made up of following component:
Somatostatin 1 part
10 ~ 100 parts of mannitol
The tert-butyl alcohol 8 ~ 25 parts
PH regulator is appropriate
Water for injection is appropriate
Wherein, described PH regulator can be the one or two kinds of in glacial acetic acid, citric acid, lactic acid, hydrochloric acid, glycine,
PH regulator regulation pH value is 4.0 ~ 6.0.
2. somatostatin freeze-dried powder as claimed in claim 1, it is characterised in that with mass ratio range, somatostatin: mannitol
=1:20 ~ 50.
3. somatostatin freeze-dried powder as claimed in claim 1, it is characterised in that with mass ratio range, somatostatin: mannitol
=1:30.
4. somatostatin freeze-dried powder as claimed in claim 1, it is characterised in that with mass ratio range, somatostatin: the tert-butyl alcohol
=1:16.
5. the preparation method of the somatostatin freeze-dried powder described in a claim 1, it is characterised in that this preparation method includes
Following steps:
(1) weigh the mannitol of 10 ~ 100 parts of weight portions, add a certain amount of water for injection, stirring and dissolving, add 8 ~ 25 parts of weights
The tert-butyl alcohol of amount part, stirring and dissolving, add the somatostatin of 1 part of weight portion, stirring makes principal agent be completely dissolved；
(2) add appropriate activated carbon, stir 15 ~ 30 minutes, de-charcoal；
(3) benefit adds to the full amount of water for injection, and using PH regulator regulation pH value is 4.0 ~ 6.0, and the process of making up a prescription carries out filling indifferent gas
Body is protected；
(4) fill: by liquid medicine filling in ampoule bottle, lyophilizing；
(5) freeze-drying curve: after the goods inlet that fill obtains, is cooled to-35 ± 5 DEG C of pre-freezes, keeps 1 ~ 3 hour；It is warming up to-15
± 5 DEG C, it is incubated 2 ~ 3 hours, then is cooled to-35 ± 5 DEG C of insulations 1 ~ 3 hour；Open cold-trap, open vacuum；Baffle temperature is warming up to-
15 ~-10 DEG C, then keep 5 ~ 10 hours；Baffle temperature is warming up to-5 ~ 5 DEG C, then keeps 3 ~ 5 hours；Again by baffle temperature
It is warming up to 25 ~ 40 DEG C, then keeps 3 ~ 5 hours；After lyophilizing terminates, filling with inert gas under vacuum state, take the dish out of the pot；
(6) drawing envelope: drawn by the ampoule after lyophilizing and seal and get final product, when drawing envelope, ambient humidity is relative humidity 15% ~ 40%.
6. somatostatin freeze-dried powder preparation method as claimed in claim 5, it is characterised in that described noble gas be nitrogen,
One in carbon dioxide, argon.
7. somatostatin freeze-dried powder preparation method as claimed in claim 5, it is characterised in that draw ambient temperature control during envelope
System is at 15 DEG C ~ 20 DEG C.
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| CN114146164B (en) * | 2021-12-09 | 2023-05-23 | 海南皇隆制药股份有限公司 | Somatostatin preparation for injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103222963A (en) * | 2013-05-24 | 2013-07-31 | 成都天台山制药有限公司 | Somatostatin freeze-dried powder injection |
| CN103417499A (en) * | 2013-07-25 | 2013-12-04 | 武汉华龙生物制药有限公司 | Preparation method of somatostatin freeze-dried powder injection |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103222963A (en) * | 2013-05-24 | 2013-07-31 | 成都天台山制药有限公司 | Somatostatin freeze-dried powder injection |
| CN103417499A (en) * | 2013-07-25 | 2013-12-04 | 武汉华龙生物制药有限公司 | Preparation method of somatostatin freeze-dried powder injection |
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