CN108785258A - A kind of Plerixafor preparation and preparation method thereof - Google Patents
A kind of Plerixafor preparation and preparation method thereof Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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Abstract
The invention belongs to chemical medicine preparation technique field, it is related to a kind of Plerixafor preparation and preparation method thereof, the Plerixafor preparation includes active constituent Plerixafor and auxiliary material, and the auxiliary material is excipient, antioxidant and pH adjusting agent；The each component is that weight part ratio is：Plerixafor：Excipient：Antioxidant=1-100:1-1000:1-50；The pH adjusting agent is used to adjust the pH to 4.0 ~ 9.0 of solution.Since the aqueous solution of Plerixafor is unstable, be easy oxidative degradation, to production and storage request it is extremely stringent, therefore product production and carrying cost it is higher.The present invention avoids various adverse reactions caused by the unstable degradation in clinical application due to product the study found that the stability that Plerixafor will be greatly improved in freeze-dried powder is made in Plerixafor；Production process is simplified simultaneously, production technology controllability is good；And storage and transportation is convenient, greatly reduces the production cost and risk of product.
Description
Technical field
The invention belongs to chemical medicine preparation technique field, it is related to a kind of Plerixafor preparation and preparation method thereof.
Background technology
The chemical constitution of Plerixafor is：
Plerixafor（plerixafor）Entitled 1,1'- [the 1,4- benzene two of chemistry（Methylene）] four nitrogen of-two -1,4,8,11-
The heterocycle tetradecane；For white to off-white color crystalline solid；Draw moist with reversible, tetrahydrate can be formed at high humidity；Have
Eight alkaline amine function groups, have strong basicity, are slightly soluble in water, are soluble in organic solvent methanol, 1- octanols, propylene glycol, and ethyl alcohol is different
Propyl alcohol and pH are less than 10 aqueous solution.
The formulation products of Genzyme companies of U.S. research and development, trade name Mozobil, on December 15th, 2008 pass through FDA batches
Standard lists in the U.S., and on July 31st, 2009 is ratified to list in European Union by EMA, which is injection, specification 24MG/
1.2ML (20MG/ML), subcutaneous administrations.Mozobil（A kind of hematopoietic stem cell mobilization agent）It is suitable for and granular leukocyte colony
Stimulating factor（G-CSF）It shares, is used for candidate stem cell to Mobilization, in non-Hodgkin lymphoma（NHL）Or
Huppert's disease（MM）Stem cell collection and autotransplantation are completed in patient.
Plerixafor is a kind of small molecule CXCR4 chemokine receptor anagonists, due to stromal cell derived factor-1
（SDF-1）Make candidate stem cell " migration " with " going back to the nest " in marrow with CXCR4 interactions, Plerixafor can be tied with CXCR4
It closes effectively to block the signal transduction between SDF-1 and CXCR4.Plerixafor can stimulate hemopoietic stem cell proliferation, divide simultaneously
Change and enters blood circulation.Multiple studies have shown that G-CSF is used in combination in Plerixafor, NHL and MM patients can be made to be released into peripheral blood
The quantity showed increased of middle candidate stem cell makes peripheral blood CD34+ cell masses and candidate stem cell colony increase, hence it is evident that improve
The success rate of NHL and MM autologous patient hematopoietic stem cell transplantation.
Since the aqueous solution of Plerixafor is unstable, it is easy oxidative degradation, it is extremely stringent to production and storage request, product
Production and carrying cost are higher, strongly limit its production and application.
Patent CN104069061A discloses the water-soluble of stabilization of the composition for injection of Plerixafor between pH6 to 8
Property Plerixafor sterile water solution form, the solubility of Plerixafor in aqueous solution when with liquid is improved, when reducing with liquid
Between, but the patent system it is standby Plerixafor aqueous products it is unstable, storage during be easy to happen oxidative degradation, clinical application
It is middle various adverse reactions to be caused due to the unstable degradation of product.
Invention content
The present invention is unstable for existing Plerixafor aqueous solution, and oxidizable degradation problem provides a kind of Plerixafor
Preparation and preparation method thereof, dosage form are injection freeze-dried powder, greatly improve the stability of Plerixafor, avoid clinical use
The various adverse reactions caused by the unstable degradation of product in medicine；Simplify production process, production technology controllability simultaneously
It is good；And storage and transportation is convenient, greatly reduces the production cost and risk of product.
A kind of Plerixafor preparation of the present invention, including active constituent Plerixafor and auxiliary material, the auxiliary material are figuration
Agent, antioxidant and pH adjusting agent；The each component is that weight part ratio is：Plerixafor：Excipient：Antioxidant=1-100:
1-1000:1-50。
Preferably：The each component is that weight part ratio is：Plerixafor：Excipient：Antioxidant=1-50:1-
100:1-10。
The active constituent includes Plerixafor, its water soluble salt, its hydrate or other derivatives, preferably Pu Lesha
Good fortune.
Skeletal support agent of the excipient as freeze-dried powder, on the one hand can protect main ingredient, main ingredient is prevented to be lyophilized
During adsorbed or destroyed, so that content is reduced；On the other hand, it can prevent product from collapsing, product appearance is made to shape, together
The redissolution stability of Shi Tigao products.The excipient of the present invention is selected from mannitol, sorbierite, lactose, glucose, sucrose, dextrorotation
It is one or more in sugared acid anhydride or sodium chloride, preferably one or more of mannitol, lactose or sodium chloride, most preferably sweet dew
Alcohol.
The antioxidant can prevent oxidation of Plerixafor during preparation, storage and use as stabilizer
Degradation, improves the stability of product.The antioxidant of the present invention is selected from thioglycerol, sodium thiosulfate, ascorbic acid and its derivative
Object, sodium sulfite, sodium hydrogensulfite, sodium pyrosulfite, sodium dithionite, thiocarbamide, tocopherol and its derivative, glycine,
It is one or more in methionine, cysteine, valine, niacinamide, ethylenediamine tetra-acetic acid, preferred thioglycerol, thio
It is one or more in sodium sulphate, cysteine, ethylenediamine tetra-acetic acid, most preferably thioglycerol.
Combination of two of the pH adjusting agent in inorganic acid or organic acid and inorganic base or organic base；The acid is excellent
Select acetic acid, hydrochloric acid, phosphoric acid, citric acid, most preferably hydrochloric acid；The preferred sodium hydroxide of the alkali, sodium bicarbonate, sodium citrate, carbonic acid
Potassium, most preferably sodium hydroxide.
PH to 4.0 ~ 9.0 of the pH adjusting agent for adjusting solution, preferably pH6.0 ~ 7.5, most preferably pH6.7 ~
6.9。
A kind of preparation method of injection Plerixafor provided by the invention, adopts the following technical scheme that：
A kind of preparation method of injection Plerixafor, includes the following steps：
（1）Excipient and antioxidant are weighed by formula, is dissolved in sterile water for injection；Plerixafor is added by formula, stirs
It mixes to form slurries；
（2）PH adjusting agent is added in above-mentioned slurries, active component is made to dissolve, and pH value is adjusted within the scope of formula regulation pH,
It is settled to prescribed volume；
（3）It dispenses after filtering with microporous membrane, is aseptically freeze-dried, the pre-freeze 1-5 at -30 DEG C to -60 DEG C
Hour, then carry out vacuum freezedrying；The primary drying time, redrying was in 2-15 hours between 10-30 hours
Between, constant temperature time made dried frozen aquatic products moisture≤3% to get to Plerixafor preparation at 1-5 hours.
Beneficial effects of the present invention：Since the aqueous solution of Plerixafor is unstable, it is easy oxidative degradation, present invention research hair
It is existing, the stability that freeze drying powder injection will greatly improve active constituent Plerixafor in Plerixafor preparation is made in Plerixafor.
After stability test is studied, it is found that its active constituent Plerixafor stability greatly improves, the oxidation impurities of degradation are reduced,
Under identical condition of storage, stability and drug effect phase have obtained great extension.
Specific implementation mode
Form is described in further detail the above of the present invention again by the following examples, but it may be noted that
It is that these embodiments are merely to illustrate the present invention and do not limit the scope of the invention, all to be realized based on the above of the present invention
Technology all belong to the scope of the present invention.
Embodiment 1
Plerixafor 24g
Ethylenediamine tetra-acetic acid 0.48g
Lactose 24g
Hydrochloric acid tune pH 4.5 ± 0.5
It is made 1000
Ethylenediamine tetra-acetic acid and appropriate lactose are weighed, is dissolved in sterile water for injection, a certain amount of activity is added by formula
Component Plerixafor, stirring forms slurries, with 10% dissolving with hydrochloric acid, and pH values is adjusted to 4.5 ± 0.5, is settled to 1200ml.
Through 0.22 μm of filtering with microporous membrane, the content of Plerixafor in solution is measured, west is sub-packed in by every bottle of Plerixafor containing 24mg
In woods bottle, aseptically it is freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, then carries out freezing vacuum
It is dry.The primary drying time, between 2-15 hours, constant temperature time made redrying at 1-5 hours between 10-30 hours
The control of dried frozen aquatic products moisture is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 2
Plerixafor 24g
Sodium thiosulfate 0.24g
Sorbierite 48g
Acetic acid tune pH 5.5 ± 0.5
It is made 1000
Sodium thiosulfate and appropriate sorbierite are weighed, is dissolved in sterile water for injection, a certain amount of activity is added by formula
Component Plerixafor, stirring forms slurries, with 5% acetate dissolution, and pH values is adjusted to 5.5 ± 0.5, is settled to 1200ml.
Through 0.22 μm of filtering with microporous membrane, the content of Plerixafor in solution is measured, west is sub-packed in by every bottle of Plerixafor containing 24mg
In woods bottle, aseptically it is freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, then carries out freezing vacuum
It is dry.The primary drying time, between 2-15 hours, constant temperature time made redrying at 1-5 hours between 10-30 hours
The control of dried frozen aquatic products moisture is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 3
Plerixafor 24g
Thioglycerol 0.24g
Mannitol 12g
Hydrochloric acid tune pH 6.7 ± 0.5
It is made 1000
Thioglycerol and appropriate mannitol are weighed, is dissolved in sterile water for injection, a certain amount of activearm is added by formula
Point Plerixafor, stirring form slurries, with 10% dissolving with hydrochloric acid, and pH values are adjusted to 6.7 ± 0.5, are settled to 1200ml.Through
0.22 μm of filtering with microporous membrane measures the content of Plerixafor in solution, XiLin is sub-packed in by every bottle of Plerixafor containing 24mg
It in bottle, is aseptically freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, it is dry then to carry out freezing vacuum
It is dry.The primary drying time, for redrying between 2-15 hours, constant temperature time made jelly at 1-5 hours between 10-30 hours
The control of dry product moisture is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 4
Plerixafor 24g
Cysteine 0.06g
Sodium chloride 12g
H7.5 ± 0.5 citric acid tune p
It is made 1000
Cysteine and appropriate sodium chloride are weighed, is dissolved in sterile water for injection, a certain amount of activearm is added by formula
Divide Plerixafor, stirring to form slurries, is dissolved with 20% citric acid, and pH values are adjusted to 7.5 ± 0.5, be settled to 1200ml.
Through 0.22 μm of filtering with microporous membrane, the content of Plerixafor in solution is measured, west is sub-packed in by every bottle of Plerixafor containing 24mg
In woods bottle, aseptically it is freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, then carries out freezing vacuum
It is dry.The primary drying time, between 2-15 hours, constant temperature time made redrying at 1-5 hours between 10-30 hours
The control of dried frozen aquatic products moisture is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 5
Plerixafor 24g
Sodium hydrogensulfite 0.12g
Sucrose 5g
Hydrochloric acid tune pH 8.0 ± 0.5
It is made 1000
Sodium hydrogensulfite and appropriate sucrose are weighed, is dissolved in sterile water for injection, a certain amount of activearm is added by formula
Point Plerixafor, stirring form slurries, with 20% dissolving with hydrochloric acid, and pH values are adjusted to 8.0 ± 0.5, are settled to 1200ml.Through
0.22 μm of filtering with microporous membrane measures the content of Plerixafor in solution, XiLin is sub-packed in by every bottle of Plerixafor containing 24mg
It in bottle, is aseptically freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, it is dry then to carry out freezing vacuum
It is dry.The primary drying time, for redrying between 2-15 hours, constant temperature time made jelly at 1-5 hours between 10-30 hours
The control of dry product moisture is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 6
Plerixafor 24g
Ascorbic acid 0.12g
Sucrose 12g
Hydrochloric acid tune pH 8.5 ± 0.5
It is made 1000
Ascorbic acid and appropriate sucrose are weighed, is dissolved in sterile water for injection, a certain amount of active component is added by formula
Plerixafor, stirring forms slurries, with 5% dissolving with hydrochloric acid, and pH values is adjusted to 8.5 ± 0.5, is settled to 1200ml.Through
0.22 μm of filtering with microporous membrane measures the content of Plerixafor in solution, XiLin is sub-packed in by every bottle of Plerixafor containing 24mg
It in bottle, is aseptically freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, it is dry then to carry out freezing vacuum
It is dry.The primary drying time, for redrying between 2-15 hours, constant temperature time made jelly at 1-5 hours between 10-30 hours
The control of dry product moisture is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 7
Plerixafor 24g
Thioglycerol 0.12g
Sucrose 12g
Citric acid tune pH 7.0 ± 0.5
It is made 1000
Thioglycerol and appropriate sucrose are weighed, is dissolved in sterile water for injection, a certain amount of active component is added by formula
Plerixafor, stirring form slurries, are dissolved with 10% citric acid, and pH values are adjusted to 7.0 ± 0.5, are settled to 1200ml.Through
0.22 μm of filtering with microporous membrane measures the content of Plerixafor in solution, XiLin is sub-packed in by every bottle of Plerixafor containing 24mg
It in bottle, is aseptically freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, it is dry then to carry out freezing vacuum
It is dry.The primary drying time, for redrying between 2-15 hours, constant temperature time made jelly at 1-5 hours between 10-30 hours
The control of dry product moisture is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 8
Plerixafor 24g
Cysteine 0.24g
Lactose 12g
Phosphoric acid tune pH 8.5 ± 0.5
It is made 1000
Cysteine and appropriate lactose are weighed, is dissolved in sterile water for injection, a certain amount of active component is added by formula
Plerixafor, stirring form slurries, are dissolved with 20% phosphoric acid, and pH value is adjusted to 8.5 ± 0.5, are settled to 1200ml.Through 0.22
μm filtering with microporous membrane, measure solution in Plerixafor content, be sub-packed in cillin bottle by every bottle of Plerixafor containing 24mg
In, it is aseptically freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, then carries out vacuum freezedrying.
The primary drying time, for redrying between 2-15 hours, constant temperature time made dried frozen aquatic products at 1-5 hours between 10-30 hours
Moisture control is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 9
Plerixafor 24g
Ascorbic acid 0.12g
Mannitol 12g
Hydrochloric acid tune pH 6.5 ± 0.5
It is made 1000
Ascorbic acid and appropriate mannitol are weighed, is dissolved in sterile water for injection, a certain amount of activearm is added by formula
Point Plerixafor, stirring form slurries, with 5% dissolving with hydrochloric acid, and pH values are adjusted to 6.5 ± 0.5, are settled to 1200ml.Through
0.22 μm of filtering with microporous membrane measures the content of Plerixafor in solution, XiLin is sub-packed in by every bottle of Plerixafor containing 24mg
It in bottle, is aseptically freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, it is dry then to carry out freezing vacuum
It is dry.The primary drying time, for redrying between 2-15 hours, constant temperature time made jelly at 1-5 hours between 10-30 hours
The control of dry product moisture is 3% hereinafter, obtaining injection Plerixafor.
Embodiment 10
Plerixafor 24g
Sodium thiosulfate 0.12g
Mannitol 12g
Hydrochloric acid tune pH 5.5 ± 0.5
It is made 1000
Sodium thiosulfate and appropriate mannitol are weighed, is dissolved in sterile water for injection, a certain amount of activity is added by formula
Component Plerixafor, stirring forms slurries, with 5% dissolving with hydrochloric acid, and pH values is adjusted to 5.5 ± 0.5, is settled to 1200ml.
Through 0.22 μm of filtering with microporous membrane, the content of Plerixafor in solution is measured, west is sub-packed in by every bottle of Plerixafor containing 24mg
In woods bottle, aseptically it is freeze-dried, pre-freeze 1-5 hours at -30 DEG C to -60 DEG C, then carries out freezing vacuum
It is dry.The primary drying time, between 2-15 hours, constant temperature time made redrying at 1-5 hours between 10-30 hours
The control of dried frozen aquatic products moisture is 3% hereinafter, obtaining injection Plerixafor.
Stability study data：
Own product is prepared using prescription in embodiment 3 and technique, add sterile water for injection redissolve after check character, pH value, content,
Related substance.Reference substance is prepared using prescription in embodiment 4 in patent CN104069061A and technique, character is checked, pH value, contains
Amount, related substance.Own product, reference substance and original are ground into product and carry out study on the stability, is placed 10 days under the conditions of being respectively placed in 60 DEG C,
It is placed 6 months under the conditions of 40 DEG C, checks character, pH value, content, related substance.It the results are shown in Table 1.It can be seen that from result, 60 DEG C of items
It is placed 6 months under the conditions of being placed 10 days and 40 DEG C under part, the related substance increasing degree of own product is smaller, and respectively less than 0.2%,
It is substantially better than reference substance and the former stability for grinding product.
1 study on the stability experimental result of table
Claims (9)
1. a kind of Plerixafor preparation, which is characterized in that dosage form is injection freeze-dried powder, including active constituent Plerixafor
And auxiliary material, the auxiliary material are excipient, antioxidant and pH adjusting agent.
2. Plerixafor preparation as described in claim 1, which is characterized in that each component is that weight part ratio is：It is general
Le Shafu：Excipient：Antioxidant=1-100:1-1000:1-50.
3. Plerixafor preparation as claimed in claim 2, which is characterized in that each component is that weight part ratio is：It is general
Le Shafu：Excipient：Antioxidant=1-50:1-100:1-10.
4. Plerixafor preparation as described in claim 1, which is characterized in that the active constituent is Plerixafor, including
But it is not limited to its water soluble salt, its hydrate or other derivatives.
5. such as claim 1 ~ 3 any one of them Plerixafor preparation, which is characterized in that the excipient is selected from sweet dew
It is one or more in alcohol, sorbierite, lactose, glucose, sucrose, dextran or sodium chloride, preferably mannitol, lactose or chlorine
Change one or more of sodium, most preferably mannitol.
6. such as claim 1 ~ 3 any one of them Plerixafor preparation, which is characterized in that the antioxidant is selected from thio sweet
Oil, sodium thiosulfate, ascorbic acid and its derivative, sodium sulfite, sodium hydrogensulfite, sodium pyrosulfite, sodium dithionite,
In thiocarbamide, tocopherol and its derivative, glycine, methionine, cysteine, valine, niacinamide, ethylenediamine tetra-acetic acid
It is one or more, it is preferably one or more in thioglycerol, sodium thiosulfate, cysteine, ethylenediamine tetra-acetic acid, most preferably
Thioglycerol.
7. Plerixafor preparation as described in claim 1, which is characterized in that the pH adjusting agent is selected from inorganic acid or organic
Combination of two in acid and inorganic base or organic base；The acid preferably acetic acid, hydrochloric acid, phosphoric acid, citric acid, most preferably hydrochloric acid；Institute
State the preferred sodium hydroxide of alkali, sodium bicarbonate, sodium citrate, potassium carbonate, most preferably sodium hydroxide.
8. Plerixafor preparation as claimed in claim 7, which is characterized in that the pH adjusting agent is used to adjust the pH of solution
To 4.0 ~ 9.0, preferably pH6.0 ~ 7.5, most preferably pH6.7 ~ 6.9.
9. according to a kind of preparation method of Plerixafor preparation of claim 1 ~ 3 any one of them, which is characterized in that including such as
Lower step：
（1）Excipient and antioxidant are weighed by formula, is dissolved in sterile water for injection；Plerixafor is added by formula, stirs
It mixes to form slurries；
（2）PH adjusting agent is added in above-mentioned slurries, active component is made to dissolve, and pH value is adjusted within the scope of formula regulation pH,
It is settled to prescribed volume；
（3）It dispenses after filtering with microporous membrane, is aseptically freeze-dried, the pre-freeze 1-5 at -30 DEG C to -60 DEG C
Hour, then carry out vacuum freezedrying；The primary drying time, redrying was in 2-15 hours between 10-30 hours
Between, constant temperature time made dried frozen aquatic products moisture≤3% to get to Plerixafor preparation at 1-5 hours.
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| CN110123742A (en) * | 2019-03-29 | 2019-08-16 | 四川汇宇制药有限公司 | A kind of preparation method of high-quality Plerixafor injection |
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| CN101167722A (en) * | 2007-10-22 | 2008-04-30 | 鲁南制药集团股份有限公司 | Ketorolac tromethamine freezing-dried power injection and preparation method thereof |
| CN104069061A (en) * | 2013-03-26 | 2014-10-01 | 江苏奥赛康药业股份有限公司 | Plerixafor-containing composition for injection, and preparation method and application thereof |
| WO2014160232A2 (en) * | 2013-03-14 | 2014-10-02 | The University Of Toledo | Injectable biodegradable bone matrix for multiple myeloma lesion augmentation and osteoporosis |
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| CN101167722A (en) * | 2007-10-22 | 2008-04-30 | 鲁南制药集团股份有限公司 | Ketorolac tromethamine freezing-dried power injection and preparation method thereof |
| WO2014160232A2 (en) * | 2013-03-14 | 2014-10-02 | The University Of Toledo | Injectable biodegradable bone matrix for multiple myeloma lesion augmentation and osteoporosis |
| CN104069061A (en) * | 2013-03-26 | 2014-10-01 | 江苏奥赛康药业股份有限公司 | Plerixafor-containing composition for injection, and preparation method and application thereof |
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| CN110123742A (en) * | 2019-03-29 | 2019-08-16 | 四川汇宇制药有限公司 | A kind of preparation method of high-quality Plerixafor injection |
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Application publication date: 20181113 |