CN102204889B - Degarelix acetate lyophilized powder injection and preparation method thereof - Google Patents
Degarelix acetate lyophilized powder injection and preparation method thereof Download PDFInfo
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Abstract
The invention provides a degarelix acetate lyophilized powder injection, which consists of degarelix acetate, mannitol and sodium acetate in the mass ratio of 1:(1.2-2):(0.02-0.1). The lyophilized powder injection is obtained by performing freeze drying on the degarelix acetate, the mannitol and the sodium acetate serving as main medicaments. In the preparation process, the stability and safety of a preparation are ensured strictly. The prepared degarelix acetate lyophilized powder injection has the advantages of low content of relevant substances, uniform and stable mass, complete moisture drying, stability in transportation, storage and using processes, convenience for clinical application, high stability and high biological activity, and the like. The preparation method adopted by the invention is simple and effective, has high repeatability and low production cost, and is easy for industrial production.
Description
Technical field
The present invention relates to the pharmaceutical technology field, specifically, relate to a kind of injection acetic acid ground and add Rake lyophilized injectable powder and preparation method thereof.
Background technology
Acetic acid ground adds the medicine that Rake is a kind of new treatment advanced prostate cancer developed by Ferring (brightness icepro) company; this medicine obtained the drugs approved by FDA listing on the 24th in December in 2008; trade name Firmagon; its chemistry D-aminopropanamide by name; the hydrogen-2 of N-acetyl group-3-(2-naphthalene)-D-lactams-4-chloro-D-phenylalanyl-3-(3-pyridine)-D-alanyl-L-seryl-4-[[[(4S)-six; 6-dioxygen-4-pyrimidine] carbonyl] amino]-L-hydrocinnamoyl-4-[(amino carbonyl) amino]-D-hydrocinnamamide base-L leucyl--N6-(1-Methylethyl)-L-lysyl-L-prolyl (base); molecular weight 1692, molecular formula C
82H
103N
18O
16Cl, structural formula is as follows:
Carcinoma of prostate sickness rate in recent years increases day by day, has become the male tumor type that case fatality rate ranks among the best.Europe sickness rate in 2006 is about 0.11%, and the number of the infected of U.S.'s carcinoma of prostate in 2008 is 186320, and death toll is 28660, mortality rate 15.4%.Studies show that testosterone levels becomes positive correlation with prostatitis adenocarcinoma value-added speed, if testosterone not with the combination of the androgen receptor that can express at most of patients with prostate cancer, apoptosis will take place in cancerous cell.Gonadotropin releasing hormone (GnRH) receptor stimulating agent and GnRH receptor antagonist all can be used for controlling testosterone levels.Degarelix is the second filial generation GnRH receptor antagonist for anti-carcinoma of prostate, has compared its distinct advantages with GnRH receptor stimulating agent and other GnRH receptor antagonist.By fast, effectively, keep development and the speed of growth that testosterone suppresses to control carcinoma of prostate, this product can prolong patient's time-to-live to the quick control of prostate specific antigen (PSA) level, its toleration is suitable with present standard care medicine at least, overcome the shortcoming of other GnRH inhibitor, can not cause the testosterone fluctuation, and nothing causes the untoward reaction of serious general, thus might develop into a line medicine in future, for treatment of prostate cancer provides new selection.
It is a kind of small peptide that acetic acid ground adds Rake, is easier to degraded, and existing acetic acid ground adds the Rake preparation and has unsettled defective, therefore need to research and develop a kind of safe, stable, effectively prepare acetic acid ground and add the Rake preparation.
Summary of the invention
The purpose of this invention is to provide a kind of acetic acid ground with good safety and stability and add the Rake lyophilized injectable powder.
Another object of the present invention provides the preparation method that this acetic acid ground adds the Rake lyophilized injectable powder, the acetic acid ground that this method makes adds Rake lyophilized injectable powder stability and improves greatly, make its stability and safety in preparation, transportation, storage and use better, it is convenient that clinical use also becomes.
In order to realize the object of the invention, a kind of acetic acid of the present invention ground adds the Rake lyophilized injectable powder, adds Rake, mannitol and sodium acetate by acetic acid ground and forms, and three's weight ratio is 1: (1.2～2): (0.02～0.1).
Wherein, preferably: the weight ratio that acetic acid ground adds Rake, mannitol and sodium acetate is 1: (1.5～2): (0.05～0.1).
Acetic acid of the present invention ground adds the preparation method of Rake lyophilized injectable powder, and it comprises the steps:
1) takes by weighing mannitol and sodium acetate by proportioning, add institute's water requirement 90% water for injection, dissolve and stir, add acetic acid ground again and add Rake, dissolving stirs, and transfers pH to 5.0～7.4 with 0.5mol/L acetic acid or 0.1mol/L sodium hydroxide solution, adds to the full amount of water for injection;
2) extremely clear and bright through 0.22 μ m filtering with microporous membrane, form through lyophilization again.
Described cryodesiccated process is: in freeze drying box, cooling earlier, after products temperature reaches-40 ℃, kept 2～3 hours, and when the condenser valve temperature reaches-45 ℃, opened vacuum pump, when vacuum reaches 20Pa when following, begin the sublimation drying that heats up, 25 ℃ of final drying temperature kept this temperature 2～4 hours.
It is a kind of gonadotropin releasing hormone (GnRH) acceptor inhibitor analog that acetic acid ground adds Rake, and reversibility suppresses hypophysis GnRH receptor and reduces the release that promoting sexual gland hormone release suppresses testosterone then.Acetic acid of the present invention ground adds the Rake lyophilized injectable powder can delay carcinoma of prostate growth and deterioration by suppressing that carcinoma of prostate is continued the vital testosterone of growth, is used for the treatment of carcinoma of prostate.
Lyophilized injectable powder of the present invention adds Rake, mannitol and sodium acetate by principal agent acetic acid ground and obtains after lyophilization, its preparation process strict guarantee stability of formulation and safety, it is low that the acetic acid ground of preparation adds Rake lyophilized injectable powder related substance (aminoacid and little peptide) content, the quality stable homogeneous, moisture drying is thorough, stable, clinical easy to use in transportation, storage and use, have stable, biological activity advantages of higher.The preparation method that the present invention adopts is simply effective, good reproducibility, and production cost is low, easy industrialized production.
The specific embodiment
Following examples are used for explanation the present invention, but are not used for limiting the scope of the invention.
Embodiment 1
Accurately take by weighing mannitol and sodium acetate, add 90% water for injection, dissolve and stir, add acetic acid ground again and add Rake, dissolving stirs, and transfers pH to 5.0 with 0.5mol/L acetic acid or 0.1mol/L sodium hydroxide solution, through intermediate after the assay was approved, add to the full amount of water for injection.Solution pump is delivered in the sterilizing room, to clear and bright, presses the loading amount fill of every bottle of 4ml through 0.22 μ m filtering with microporous membrane in the 10ml cillin bottle, adds butyl rubber bung, sabot.The lyophilizing sample for the treatment of of sabot is placed freeze drying box, close chamber door, start, cooling after products temperature reaches-40 ℃, kept 3 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum pump, when vacuum reaches 20Pa when following, begin the sublimation drying that heats up, 25 ℃ of final drying temperature, kept this temperature 2 hours, last tamponade, outlet, with plastic-aluminum composite cover tying, the qualified back of quality inspection packing gets final product.
Embodiment 2
Accurately take by weighing mannitol and sodium acetate, add 90% water for injection, dissolve and stir, add acetic acid ground again and add Rake, dissolving stirs, and transfers pH to 7.4 with 0.5mol/L acetic acid or 0.1mol/L sodium hydroxide solution, through intermediate after the assay was approved, add to the full amount of water for injection.Solution pump is delivered in the sterilizing room, to clear and bright, presses the loading amount fill of every bottle of 4ml through 0.22 μ m filtering with microporous membrane in the 10ml cillin bottle, adds butyl rubber bung, sabot.The lyophilizing sample for the treatment of of sabot is placed freeze drying box, close chamber door, start, cooling after products temperature reaches-40 ℃, kept 2 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum pump, when vacuum reaches 20Pa when following, begin the sublimation drying that heats up, 25 ℃ of final drying temperature, kept this temperature 4 hours, last tamponade, outlet, with plastic-aluminum composite cover tying, the qualified back of quality inspection packing gets final product.
Embodiment 3
Accurately take by weighing mannitol and sodium acetate, add 90% water for injection, dissolve and stir, add acetic acid ground again and add Rake, dissolving stirs, and transfers pH to 6.5 with 0.5mol/L acetic acid or 0.1mol/L sodium hydroxide solution, through intermediate after the assay was approved, add to the full amount of water for injection.Solution pump is delivered in the sterilizing room, to clear and bright, presses the loading amount fill of every bottle of 4ml through 0.22 μ m filtering with microporous membrane in the 10ml cillin bottle, adds butyl rubber bung, sabot.The lyophilizing sample for the treatment of of sabot is placed freeze drying box, close chamber door, start, cooling after products temperature reaches-40 ℃, kept 3 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum pump, when vacuum reaches 20Pa when following, begin the sublimation drying that heats up, 25 ℃ of final drying temperature, kept this temperature 3 hours, last tamponade, outlet, with plastic-aluminum composite cover tying, the qualified back of quality inspection packing gets final product.
Embodiment 4
Accurately take by weighing mannitol and sodium acetate, add 90% water for injection, dissolve and stir, add acetic acid ground again and add Rake, dissolving stirs, and transfers pH to 6.0 with 0.5mol/L acetic acid or 0.1mol/L sodium hydroxide solution, through intermediate after the assay was approved, add to the full amount of water for injection.Solution pump is delivered in the sterilizing room, to clear and bright, presses the loading amount fill of every bottle of 4ml through 0.22 μ m filtering with microporous membrane in the 10ml cillin bottle, adds butyl rubber bung, sabot.The lyophilizing sample for the treatment of of sabot is placed freeze drying box, close chamber door, start, cooling after products temperature reaches-40 ℃, kept 2 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum pump, when vacuum reaches 20Pa when following, begin the sublimation drying that heats up, 25 ℃ of final drying temperature, kept this temperature 4 hours, last tamponade, outlet, with plastic-aluminum composite cover tying, the qualified back of quality inspection packing gets final product.
Embodiment 5
Accurately take by weighing mannitol and sodium acetate, add 90% water for injection, dissolve and stir, add acetic acid ground again and add Rake, dissolving stirs, and transfers pH to 7.0 with 0.5mol/L acetic acid or 0.1mol/L sodium hydroxide solution, through intermediate after the assay was approved, add to the full amount of water for injection.Solution pump is delivered in the sterilizing room, to clear and bright, presses the loading amount fill of every bottle of 6ml through 0.22 μ m filtering with microporous membrane in the 25ml cillin bottle, adds butyl rubber bung, sabot.The lyophilizing sample for the treatment of of sabot is placed freeze drying box, close chamber door, start, cooling after products temperature reaches-40 ℃, kept 2 hours, then open condenser valve, when the condenser valve temperature reaches-45 ℃, open vacuum pump, when vacuum reaches 20Pa when following, begin the sublimation drying that heats up, 25 ℃ of final drying temperature, kept this temperature 4 hours, last tamponade, outlet, with plastic-aluminum composite cover tying, the qualified back of quality inspection packing gets final product.
Embodiment 6 acetic acid ground add Rake lyophilized injectable powder determination of related substances
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia 2010 version two ones)
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; (regulating pH value to 5.0 with triethylamine)-acetonitrile (80: 20) is mobile phase with the 0.1mol/L phosphoric acid solution, and the detection wavelength is 420nm.Getting acetic acid ground, to add Rake and glutathion (interior mark) an amount of, precision takes by weighing, be dissolved in water and be diluted to 1ml and contain the solution that acetic acid ground adds Rake 0.2mg, oxidisability glutathion 0.2mg, precision is measured 20 μ l and is injected the good chromatograph of liquid of balance, the record chromatogram, obtain as a result number of theoretical plate and add Rake by acetic acid ground and calculate and be not less than 2000, acetic acid ground adds the separating degree of Rake and glutathion should be greater than 2.0.
Getting acetic acid ground, to add the Rake lyophilized powder an amount of, accurately claims surely, adds mobile phase dissolving and dilution and make every 1ml and contain the solution that acetic acid ground adds Rake 1mg approximately, as supplying test agent; Precision takes by weighing an amount of oxidisability glutathion standard substance, makes the solution that contains 10 μ g among every 1ml, contrast solution the most with the mobile phase dilution.Get contrast solution 20 μ l and inject the good chromatograph of liquid of balance, regulate detection sensitivity, make the peak height of main constituent chromatographic peak be about 30%～50% of full scale, precision is measured for test agent solution and each 20 μ l of contrast solution again, inject the good chromatograph of liquid of balance respectively, the chromatogram of record common recognition sample.Supply in the test agent solution chromatogram as apparent impurity peaks, record except the adjuvant peak, for each impurity area sum the test agent peak, calculating namely gets acetic acid ground and adds Rake lyophilized injectable powder related substance percentage composition.
Embodiment 7 acetic acid ground add Rake lyophilized injectable powder assay
Measure according to high performance liquid chromatography (Chinese Pharmacopoeia 2010 version two ones)
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; (regulating pH value to 5.0 with triethylamine)-acetonitrile (80: 20) is mobile phase with the 0.1mol/L phosphoric acid solution, and the detection wavelength is 420nm.Getting acetic acid ground, to add Rake and glutathion (interior mark) an amount of, precision takes by weighing, be dissolved in water and be diluted to 1ml and contain the solution that acetic acid ground adds Rake 0.2mg, oxidisability glutathion 0.2mg, precision is measured 20 μ l and is injected the good chromatograph of liquid of balance, the record chromatogram, obtain as a result number of theoretical plate and add Rake by acetic acid ground and calculate and be not less than 2000, acetic acid ground adds the separating degree of Rake and glutathion should be greater than 2.0.
Getting acetic acid ground, to add the Rake lyophilized powder an amount of, accurately claims surely, adds mobile phase dissolving and dilution and make every 1ml and contain the solution that acetic acid ground adds Rake 0.1mg approximately, and precision is measured 20 μ l and injected the good chromatograph of liquid of balance, records chromatogram; Other learns from else's experience 105 ℃, and to add the Rake reference substance an amount of for the acetic acid ground that is dried to constant weight, and being dissolved in water and being diluted to contains the solution that acetic acid ground adds Rake 0.1mg approximately among every 1ml, measure with method, calculates peak area by external standard method, namely obtains percentage composition.
Embodiment 8 acetic acid ground add the Rake quality inspection
Prepare acetic acid ground respectively by embodiment 1～5 and add the Rake lyophilized injectable powder, check outward appearance, visible foreign matters, pH value, content respectively, related substance and moisture project, result such as table 1.As seen, the acetic acid ground that adopts method provided by the invention to make adds Rake lyophilized injectable powder quality homogeneous.
Table 1 acetic acid ground adds Rake lyophilized injectable powder assay
| Embodiment | Outward appearance | Visible foreign matters | pH | Content (%) | Related substance (%) | Moisture (%) |
| 1 | White powder | Up to specification | 5.6 | 98.9 | 0.25 | 0.92 |
| 2 | White powder | Up to specification | 7.2 | 99.2 | 0.21 | 0.87 |
| 3 | White powder | Up to specification | 6.8 | 100.1 | 0.23 | 0.89 |
| 4 | White powder | Up to specification | 6.2 | 99.5 | 0.31 | 0.89 |
| 5 | White powder | Up to specification | 7.0 | 99.2 | 0.27 | 0.95 |
Embodiment 9 stability tests
Require and Chinese Pharmacopoeia version correlation method in 2010 carries out influence factor's test, accelerated test and long term test and investigates the inventive method and make stability of formulation according to " chemicals stability study technological guidance principle ".The preparation that will make by the prescription of embodiment 5 detects projects by official method, the results are shown in Table 2 and table 3.As can be seen, the acetic acid ground that makes by the inventive method adds the Rake lyophilized powder and has preferably stability.
Table 2 embodiment 5 preparation influence factor result of the tests
Table 3 embodiment 5 prescription preparation accelerated test results
Embodiment 10 safety testings
Carry out preparation security test of the present invention according to " chemicals zest, anaphylaxis and hemolytic investigative technique guideline " requirement and method, animal subject is selected rabbit for use.
1. injection acetic acid ground adds Rake to rabbit auricular vein irritation test
1.1 experimental animal: get 8 of body weight 2.0～3.0kg rabbit, male and female dual-purpose, adaptability were raised after 5 days, were divided into two groups at random, namely were divided into the sodium chloride injection matched group and injection acetic acid ground adds the Rake group.
1.2 dosage: in the clinical maximum consumption per day 120mg/d that is grown up, according to the body surface area conversion, then the rabbit consumption is 2mg/kg.
1.3 the processing method of animal: behind the last medicine 96 hours, each was organized rabbit and is divided into two groups of A, B again at random, and 2 rabbit in the dead A group in each component other places are cut auricle, fix with 10% neutral formalin solution, do histopathologic examination.B group rabbit continues normal the raising 14 days, gives over to the convalescent period observation, and then puts to death, and cuts auricle, fixes with 10% neutral formalin solution, does histopathologic examination.Concrete outcome sees Table 4-6.
Table 4 injection acetic acid ground adds Rake blood vessel irritation is tested perusal
Table 5 injection acetic acid ground adds Rake drug withdrawal blood vessel irritation test in the 96 hours result of histopathologic examination
Table 6 injection acetic acid ground adds the Rake convalescent period blood vessel irritation test result of histopathologic examination
2. injection acetic acid ground adds Rake muscle irritation is tested
2.1 experimental animal: get 8 of body weight 2.0～3.0kg rabbit, the male and female dual-purpose, adaptability was raised 5 days.
2.2 dosage: face with before, get 1 injection acetic acid ground add add again after Rake dissolves with 4ml water for injection 16ml water for injection dilute 5 times standby.Earlier rabbit left and right sides quadriceps femoris hair is cut off about 4 * 3cm before the test
2, observe the outside normal condition of rabbit quadriceps femoris.Administration: the above-mentioned medicinal liquid 1.0ml/ of injection only in each rabbit left quadriceps; 1.0ml/ 0.9% sodium chloride injection of injection in the right quadriceps femoris.Every day, drug administration by injection was 1 time, for three days on end.
2.3 the processing method of animal: behind the last medicine 96 hours, rabbit is divided into two groups of A, B at random, put to death 2 rabbit in the A group, cut injection site muscle, fix with 10% neutral formalin solution, do pathological examination.B group rabbit continues normal the raising 14 days, gives over to the convalescent period observation, and then puts to death, and cuts injection site muscle, fixes with 10% neutral formalin solution, does pathological examination.Concrete outcome sees Table 7-9.
Table 7 injection acetic acid ground adds Rake to quadriceps femoris irritation test perusal result
Table 8 injection acetic acid ground add the Rake drug withdrawal after 96 hours to muscular irritation pathological examination result
Table 9 injection acetic acid ground adds Rake convalescent period to muscular irritation pathological examination result
3. injection acetic acid ground adds the Rake sensitivity test
3.1 laboratory animal: get 24 of body weight 300～350g Cavia porcelluss, the male and female dual-purpose, adaptability was raised after 5 days, was divided into four groups at random, and namely positive controls (10% fresh albumen), negative control group, injection acetic acid ground add Rake small dose group and heavy dose of group.
3.2 dosage: before the administration, get 4 bottles (0.12g) injection land used and add Rake earlier respectively with the water for injection dissolving, solution is taken out from bottle to the greatest extent immediately, it is standby that reuse water for injection is diluted to 250ml.The above-mentioned medicinal liquid of Cavia porcellus intravenous injection is low dose of 0.5ml/ during sensitization, and heavy dose of 1.0ml/ only; The above-mentioned medicinal liquid of intravenous injection is low dose of 1.0ml/ when exciting, and heavy dose of 2.0ml/ only.
3.3 index observing: during the sensitization: observe the symptom of every animal every day.And in first, last sensitization and excite the body weight of measuring every group every animal the same day, and record; Excite: at once to 30 minutes, observe the reaction of every animal in detail after exciting, the time that symptom occurs and disappears.Concrete outcome sees Table 10.
The anaphylactoid evaluation of table 10 pair Cavia porcellus
4. injection acetic acid ground adds the test of Rake hemolytic
4.1 the preparation of blood cell suspension:
Carry out according to Chinese Pharmacopoeia version method in 2010.
4.2 the preparation of medicinal liquid:
Before the administration, get 4 bottles of (0.12g) injection acetic acid ground and add Rake earlier respectively with the water for injection dissolving, solution is taken out from bottle to the greatest extent immediately, it is standby that reuse water for injection is diluted to 250ml.
4.3 method of testing:
Get 7 in test tube, be numbered, 1-5 number pipe be for the test sample pipe, manages negative control tube No. 6, manages positive control tube No. 7.The according to the form below proportional quantity adds 2% red blood cell suspension and sodium chloride injection or distilled water successively, behind the mixing, puts immediately in 37 ℃ of calorstats and carries out incubation, and beginning was observed 1 time every 15 minutes, after 1 hour, observes once every 1 hour, observes altogether 3 hours.Concrete outcome sees Table 11.
Table 11 injection acetic acid ground adds Rake hemolytic result of the test
Be not difficult to find out that the detection by above serial safety testing project shows, the acetic acid ground that makes according to the inventive method adds the Rake freeze-dried powder preparation and uses safety.
Though above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements all belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (4)
1. an acetic acid ground adds the Rake lyophilized injectable powder, it is characterized in that, adds Rake, mannitol and sodium acetate by acetic acid ground and forms, and three's weight ratio is 1:(1.2～2): (0.02～0.1);
The preparation method that described acetic acid ground adds the Rake lyophilized injectable powder comprises the steps:
1) takes by weighing mannitol and sodium acetate by proportioning, add institute's water requirement 90% water for injection, dissolve and stir, add acetic acid ground again and add Rake, dissolving stirs, and transfers pH to 5.0～7.4 with 0.5mol/L acetic acid or 0.1mol/L sodium hydroxide solution, adds to the full amount of water for injection;
2) extremely clear and bright through 0.22 μ m filtering with microporous membrane, form through lyophilization again; Described cryodesiccated process is: in freeze drying box, cooling earlier, after products temperature reaches-40 ℃, kept 2～3 hours, and when the condenser valve temperature reaches-45 ℃, opened vacuum pump, when vacuum reaches 20Pa when following, begin the sublimation drying that heats up, 25 ℃ of final drying temperature kept this temperature 2～4 hours.
2. acetic acid according to claim 1 ground adds the Rake lyophilized injectable powder, it is characterized in that the weight ratio that acetic acid ground adds Rake, mannitol and sodium acetate is 1:(1.5～2): (0.05～0.1).
3. claim 1 or 2 described acetic acid ground add the preparation method of Rake lyophilized injectable powder, it is characterized in that it comprises the steps:
1) takes by weighing mannitol and sodium acetate by proportioning, add institute's water requirement 90% water for injection, dissolve and stir, add acetic acid ground again and add Rake, dissolving stirs, and transfers pH to 5.0～7.4 with 0.5mol/L acetic acid or 0.1mol/L sodium hydroxide solution, adds to the full amount of water for injection;
2) extremely clear and bright through 0.22 μ m filtering with microporous membrane, form through lyophilization again; Described cryodesiccated process is: in freeze drying box, cooling earlier, after products temperature reaches-40 ℃, kept 2～3 hours, and when the condenser valve temperature reaches-45 ℃, opened vacuum pump, when vacuum reaches 20Pa when following, begin the sublimation drying that heats up, 25 ℃ of final drying temperature kept this temperature 2～4 hours.
4. claim 1 or 2 described acetic acid ground add the Rake lyophilized injectable powder for the preparation of the application in the treatment carcinoma of prostate medicine.
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| CN102423484B (en) * | 2011-11-23 | 2014-01-15 | 深圳翰宇药业股份有限公司 | Stable cetrorelix medicinal composition and preparation method thereof |
| TWI580443B (en) * | 2012-06-01 | 2017-05-01 | 菲瑞茵公司 | Manufacture of degarelix |
| CN105749245A (en) * | 2016-03-02 | 2016-07-13 | 张光泉 | Anti-cancer drug degarelix acetate injection and preparation method thereof |
| CN113952297B (en) * | 2020-07-21 | 2023-04-25 | 深圳翰宇药业股份有限公司 | Degarelix-containing pharmaceutical composition for injection, and preparation method and application thereof |
| CN114460179A (en) * | 2020-11-09 | 2022-05-10 | 深圳市健翔生物制药有限公司 | Method for measuring in-vitro release degree of degarelix acetate for injection |
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