CN108403628A - A kind of Decameth - Google Patents
A kind of Decameth Download PDFInfo
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- CN108403628A CN108403628A CN201810486524.4A CN201810486524A CN108403628A CN 108403628 A CN108403628 A CN 108403628A CN 201810486524 A CN201810486524 A CN 201810486524A CN 108403628 A CN108403628 A CN 108403628A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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Abstract
The present invention relates to a kind of Decameths and preparation method thereof, the injection includes dexamethasone sodium phosphate, stabilizer, antioxidant, metal ion chelation agent, pH adjusting agent, viscosity modifier, solubilizer, osmotic pressure regulator and water for injection, high-temperature sterilization is process after dissolving, has certain viscosity.The injection of the present invention is used as injection of tympanum, and with drug absorption in tympanum is improved, improves the effect of sudden deafness.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of injection for having certain viscosity containing dexamethasone drug
Agent and preparation method thereof.
Background technology
In recent years, glucocorticoid is widely used in a variety of disease of inner ear for the treatment of, such as deaf, Meniere disease and acute meninx
Labyrinthitis etc. after inflammation.Sudden deafness is a kind of non-fluctuation phonosensitive nerve deafness occurred suddenly, and morbidity is anxious, progress
Soon, the burst of patient's hearing can be caused to decline in several minutes, a few hours or 3 days.Common concomitant symptom be mainly tinnitus and
Dizziness.Cause the cause of disease of sudden deafness not yet completely clear at present, Etiological has：Inner ear microcirculation lesion, special sexuality
Dye, immune factor and psychologic factors etc..Acute deafness is similar to the sudden deafness cause of disease, but different, acute deafness
Concomitant symptom has tinnitus but not vertigo, has scholar to think that the cause of disease of acute deafness is mainly Middle Ear Diseases.The two is adopted at present
Use hormone therapy.Hormone helps to interrupt pathology damage process, protection and promotion inner ear are every in the treatment of sudden deafness
The recovery of function.But the therapeutic effect of the inner ear tissue organ of the irreversible damage for having occurred and that is limited.Hormone is for disease
The serious patients with sudden sensorineural hearing loss curative effect of feelings is apparent, especially restores preferable to intermediate frequency and low frequency patient.It in the world will be sugared
Standard regimens of the cortin as sudden deafness.
Document report, it is dexamethasone and sodium succinate methylprednisolone (methylprednisolone) clinically to be applied at most through tympanum.
Early in McCabe in 1979 research (Annals of Otology, Rhinology and Laryngology, 1979,88
(5)：585-589) turning out can make patient's hearing apparent using corticoid treatment autoimmune phonosensitive nerve deafness
Improve.Oral dexamethasone is applied in subsequent research, intramuscular injection dexamethasone sodium phosphate injection, fills in rice to intravenous drip
The modes such as pine, tympanum interpolation pipe instillation dexamethasone, Injection in Tympanic Cavity treat sudden deafness, there is remarkable result.But internally
The treatment of ear disease, main problem existing for traditional Formulations for systemic administration pattern (oral, vein)：It is depositing for the lost barrier of blood-first
Drug is set to be difficult to reach treatment concentration in inner ear；Followed by systemic side effects are apparent.But research has shown that, dexamethasone can be through
It crosses eardrum-tympanum approach and enters inner ear (audiology and speech disease magazine, 2005,13 (4)：260-263), to be inner ear disease
The treatment of disease provides new approaches.Injection in Tympanic Cavity dosage is few, targeting is good, and drug is acted in inner ear high concentration, effectively anti-
Only the side effect of drug general action, medication are safer.
Dexamethasone has powerful anti-inflammatory work as a kind of artificial synthesized cortex hormone of aadrenaline, to each tract
With；And compared with hydrocortisone and its derivative, water-sodium retention side effect is most weak and anti-inflammatory effect is most strong.Dexamethasone biology
Half-life period is 36~54h, is Glucocorticoid (china medical abstract Otolaryngology, 2014,29 (5)：280).Office
Portion applies dexamethasone, ensures that high concentration dose acts on inner ear, this may make before irreversible transformation occurs for disease of inner ear
Save hearing loss.
Tympanum is separated by with inner ear by round window.Round window membrane (round window membrane, RWM) is to be located at tympanum and ear
One layer of membranous septum between snail, inside is perilymph (liquid phase), and outside is tympanic cavity (gas phase).It is separating tympanum and ear
It is also a potential important administration channel while snail.In drug in tympanum can directly be penetrated by round window membrane
Ear perilymph, to avoid blood-lost barrier (Chinese Journal of Otology, 2014,12 (4)：670).Lymph constantly follows
Ring, flowing are conducive to drug and are spread in film, labyrinthine system.Evidence suggests people's round window theca cell has to be passed through similar to semi-permeable membrane
The feature of approach.These institutional frameworks include the microvillus on okioplast surface, although less, this, which is round window membrane, absorption energy
The indication of power.Also result of study shows that, through the long-term successive administration of round window membrane, the structure of round window membrane is shown normally, zero defect, scar
Trace or inflammation change, and cell electrocochleogram also shows no inner hair cell loss, and external hair cell missing is also in normal range (NR)
(Audiol Neurootol, 2005,10：53-63).
The injection of the present invention has certain viscosity under the action of viscosity modifier, is that can note in the range of viscosities
The viscous liquid penetrated.Since the drum interior space is minimum, the dose that can be accommodated is seldom, through Eustachian tube stream after existing injection injection
It loses, seldom plays a role through inner ear absorption.Since the injection of the present invention has apparent viscosity compared to normal injection agent, can have
Effect extends drug in the intratympanic residence time, increases absorption of the drug in inner ear.Meanwhile the viscosity modifier selected by the present invention
Its hydrophily can be utilized to keep cell flexible, change cell shape, tissue infiltration power be improved, to increase drug absorption.
Invention content
The object of the present invention is to provide a kind of using dexamethasone as the injection with certain viscosity of active constituent, effectively
Ground solves the problems such as whole body application side effect when treating deaf of dexamethasone drug is more, and the topical application residence time is few.
To achieve the goals above, present invention employs following technical solutions：
The invention discloses a kind of using dexamethasone as the injection of active constituent, by dexamethasone and pharmaceutically acceptable
Auxiliary material forms, it is characterised in that pharmaceutically acceptable auxiliary material includes but not limited to antioxidant, stabilizer, pH adjusting agent, infiltration
Press one or more of conditioning agent, viscosity modifier, solubilizer and metal ion chelation agent.The injection of the present invention can be optional
Ground includes water, i.e. said preparation can be aqueous liquid preparation, such as glycerol injections agent, can also be to be diluted to fit before use
The glycerol injections agent of injection is closed, or can also be the preparation for redissolving the dried forms for being liquid preparation before use, as glycerine freezes
Dry preparation.
The injection of the present invention has certain viscosity, (range in the range of viscosities under the action of viscosity modifier
In 5.37-24.26cP) be injectable viscous liquid.Since the drum interior space is minimum, the dose that can be accommodated is seldom, common to note
It is lost in through Eustachian tube after penetrating agent injection, seldom plays a role through inner ear absorption.Since the injection of the present invention is compared to common note
Penetrating agent has apparent viscosity, can effectively extend drug in the intratympanic residence time, increase absorption of the drug in inner ear.Meanwhile
Viscosity modifier selected by the present invention can utilize its hydrophily to keep cell flexible, change cell shape, improve tissue infiltration power, from
And increase drug absorption.
The prescription and preparation method of injection of the present invention are as follows：
Preparation method is：
(1) preparation of solvent：It weighs suitable phosphate and is configured to the phosphate buffer of pH8.0 or by suitable viscosity-adjusting agent
The phosphate buffer of agent and water for injection or pH8.0 is uniformly mixed；
(2) supplementary material for weighing recipe quantity is dissolved into 50ml with above-mentioned solvent and is adjusted to 8.0 with pH adjusting agent；
(3) it will be sub-packed in ampoule after liquid aseptic filtration；
After (4) 100 DEG C of flowing steam sterilization 15min to obtain the final product.
In injection of the present invention, dexamethasone drug particle size is less than 200 mesh.
It is characterized in that, the viscosity modifier is glycerine or Sodium Hyaluronate, and gained injection fluid viscosity is 5.37-
24.26cP。
The antioxidant is sodium hydrogensulfite；
The stabilizer is propylene glycol；
The pH adjusting agent is sodium hydroxide or hydrochloric acid；
The metal ion chelation agent is EDTA-2NaCa；
The solubilizer include but not limited to PLURONICS F87, polyoxyethylene sorbitan monoleate,HS15, hydroxypropyl-β-cyclodextrin.
The present invention also provides injections in the administration route for treating acute deafness.
The injection of the preferred present invention is processed by following component：
In injection of the present invention, dexamethasone sodium phosphate dosage is 20~40mg/ml, more preferable 30mg/ml.
The injection of the present invention is administered in tympanum, is absorbed by ear round window approach, administering mode is drug administration by injection.
Preparation method is as follows：
(1) preparation of solvent：Weigh suitable phosphate be configured to phosphate buffer (water for injection add to after full dose at
The buffer solution of pH8.0), and dissolve viscosity modifier；
(2) supplementary material for weighing recipe quantity is dissolved into 50ml with above-mentioned solvent and adjusts pH to 8.0；；
(3) it will be sub-packed in ampoule after liquid aseptic filtration；
After (4) 100 DEG C of flowing steam sterilization 15min to obtain the final product.
Gained injection range of viscosities is 5.37-24.26cP.
Illustrate beneficial effects of the present invention by testing as follows：
Dexamethasone sodium phosphate injection single injection of tympanum gives the exploratory experiment of machin
The purpose of experiment：
After evaluation dexamethasone sodium phosphate injection (by the preparation of embodiment 1,2,4,5) single injection of tympanum gives machin, adopt
Collect inner ear lymph, understands its metabolic characteristics in inner ear lymph, and compared with commercial preparation (5mg/ml).
1, experimental animal
Kind and strain：Machin
Animal level：Regular grade
Administration starts preceding weight：Male：2~6kg；Female：2~6kg；
Size of animal：Using 8 animals, male and female are unlimited；
Surviving animals processing：After the test, surviving animals hand over animal doctor's unified management.
2, reason is selected
The reasons why animal species select：The machin that this experiment uses be for or be envisaged for human body test sample carry out toxicity examination
Test common animal species.The duct of machin is similar to drum structure to people, is that preclinical safety evaluation experiment is common
Therefore experimental animal selects animal species of the machin as this experiment, meet science needs.
3, animal packet
8 animals are divided into 2 batches, every group 4, give 1,2,4,5 dexamethasone sodium phosphate injection sample of embodiment respectively.The
One group of dexamethasone being administered in lymph and cerebrospinal fluid for 24 hours and content determination of Dexamethasone Sodium measure, and second group is administered
Dexamethasone and content determination of Dexamethasone Sodium in 48h lymph and cerebrospinal fluid measure
4, it is administered
Administration route：Injection of tympanum
Administration frequency：Single injection.
Medication：After animal muscle injects ketamine (10mg/kg, 50mg/mL), it is injected intravenously yellow Jackets (10
~20mg/kg, 20mg/mL) implement anesthesia, before injecting post-sampling, as needed, yellow Jackets predose can be given
10%~15% carries out additional anesthesia.Administration phase need to clean duct.By endoscope and microscope device, slowly injected through tympanum
Test sample/reference substance of the various concentration of 0.3mL.External auditory canal is put into the cotton ball soaked in alcohol extracted after injection, and injection is surveyed upward
Place at least half an hour.
5, sample collection and processing (cerebrospinal fluid and inner ear lymph)
Inner ear lymph and cerebrospinal fluid：Animal is used ketamine by the 1st, 2 group of animal about 24,48 and 72h after administration
(10mg/kg, 50mg/mL) intramuscular injection, then it is injected intravenously anesthetized animal with yellow Jackets (20mg/kg, 20mg/mL), lead to
Femoral artery depletion method is crossed, after euthanizing animals, opens inner ear, quantitative inner ear lymph is added a certain amount of
The volume ratio of the phosphoric acid of 1.5mol/L, lymph and phosphoric acid is 1：9.Mixing is placed on keeps on ice, and is transferred to ultralow temperature ice
(≤- 70 DEG C) preservations of case.Simultaneous quantitative acquires cerebrospinal fluid, is added the phosphoric acid of a certain amount of 1.5mol/L, cerebrospinal fluid and phosphoric acid
Volume ratio is 1：9, mixing is placed on keeps on ice, and is transferred to (≤- 70 DEG C) preservations of ultra low temperature freezer.
Corpse after animal euthanasia is as treatment of!medical waste.
6, experimental result and discussion
The medicine codes or data (ng/ml) of first 4 monkeys, left ear test sample (1,2,4,5 sample of embodiment), the commercially available (5mg/ of auris dextra
ml)。
The medicine codes or data (ng/ml) of 4 monkeys of second batch, left ear test sample (1,2,4,5 sample of embodiment), auris dextra is commercially available
(5mg/ml)
Note：L indicates that left ear administration, R indicate auris dextra administration.
Analysis discusses
1, drug is almost not detected in cerebrospinal fluid, illustrates the advantage of tympanomastoid notch approach, the hormone Formulations for systemic administration pair avoided is made
With；
2, apparent with 48h test samples and marketed drugs difference for 24 hours after being administered, with the increase of injection fluid viscosity, drug transmitance
Increase；Illustrate that injection can stop about 48h in middle ear after injection of tympanum and play a role.
Specific implementation mode：
The present invention is further detailed by following specific examples, but not as the limitation of the present invention.It is all to be based on this
The technology that invention the above is realized all belongs to the scope of the present invention.
Embodiment 1：
Preparation method：
(1) 80% recipe quantity water for injection is taken, dissolves NaHSO successively3, EDTA-2NaCa, glycerine and dexamethasone sodium phosphate；
(2) and with 30% sodium hydroxide tune pH to 8.0, full dose is settled to water for injection；
(3) it will be sub-packed in after medical filtration in 2ml ampoules, conventional logical nitrogen, sealing；
(4) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
Gained injects fluid viscosity：1.32cP
Embodiment 2：
Preparation method：
(1) water for injection for taking 80% full dose, dissolves NaHSO successively3, EDTA-2Na, dexamethasone sodium phosphate and hyalomitome
Acid, and pH to 8.0 is adjusted, it is settled to full dose；
(2) it will be sub-packed in after medical filtration in 2ml ampoules, conventional logical nitrogen, sealing；
(3) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
Gained injects fluid viscosity：5.37cP
Embodiment 3：
Preparation method：
(1) sodium dihydrogen phosphate of recipe quantity and disodium hydrogen phosphate are dissolved with water for injection.
(2) supplementary material for weighing recipe quantity is dissolved with above-mentioned solvent, is used in combination 30% sodium hydroxide solution to be adjusted to 8.0, water for injection
It is settled to full dose；
(3) it will be sub-packed in 2ml ampoules after medical filtration degerming, conventional logical nitrogen, sealing；
(4) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
Gained injects fluid viscosity：0.70cP
Embodiment 4：
Preparation method：
(1) sodium dihydrogen phosphate of recipe quantity and disodium hydrogen phosphate are dissolved with water for injection；
(2) weighing the Sodium Hyaluronate of recipe quantity, fully swelling is stirred to dissolve in (1) solution, weighs the supplementary material of recipe quantity
It is dissolved with above-mentioned solvent, is used in combination 30% sodium hydroxide to adjust pH to 8.0, water for injection is settled to full dose；
(3) it will be sub-packed in after medical filtration in 2ml ampoules, conventional logical nitrogen, sealing；
(4) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
Gained injects fluid viscosity：10.08cP
Embodiment 5：
Preparation method：
(1) weighing the Sodium Hyaluronate of recipe quantity, fully swelling is stirred to dissolve in appropriate water for injection；
(2) supplementary material for weighing recipe quantity is dissolved with above-mentioned solvent, and 30% sodium hydroxide is used in combination to adjust pH to 8.0, water for injection
It is settled to full dose；
(3) it will be sub-packed in after medical filtration in 2ml ampoules, conventional logical nitrogen, sealing；
(4) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
Gained injects fluid viscosity：24.26cP
Embodiment 6：
Preparation method：
(1) sodium dihydrogen phosphate of recipe quantity and disodium hydrogen phosphate are dissolved with water for injection；
(2) supplementary material for weighing recipe quantity is dissolved with above-mentioned solvent and with sodium hydroxide solution tune pH to 8.0, water for injection constant volume
To full dose；
(3) it will be sub-packed in 2ml ampoules after medical filtration degerming, conventional logical nitrogen, sealing；
(4) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
Gained injects fluid viscosity：0.66cP.
Embodiment 7
Composition is with embodiment 1,2,4,5, and additional 5% mannitol is as freeze-drying holder..
Preparation process：
(1) mannitol, filtration sterilization is added before final pH is adjusted in the same previous embodiment of solution preparation method；(2) by gained medicine
Liquid is sub-packed in 5ml in borosilicate glass tube vial, is partly jumped a queue, freeze-drying, and freeze-drying terminates to pour nitrogen, jumps a queue entirely, pricks aluminium lid, system must be lyophilized
Agent.
Obtained freeze-drying preparation, after being redissolved with water for injection, viscosity is respectively：1.31cP, 5.35cP, 10.05cP, and
24.15cP。
Viscosity is declined slightly compared with corresponding liquid drugs injection, and analysis reason may be related with the material damage in freeze-drying process, together
When mannitol addition the solution viscosity after redissolution is not had an impact, from the point of view of product final viscosity data, do not influence to redissolve
Curative effect of medication afterwards.
Claims (8)
1. a kind of Decameth, by following composition：
Preparation method is as follows：
(1) preparation of solvent：Weigh suitable phosphate be configured to phosphate buffer (water for injection add to after full dose at
The buffer solution of pH8.0), and dissolve viscosity modifier；
(2) supplementary material for weighing recipe quantity is dissolved into 50ml with above-mentioned solvent and adjusts pH to 8.0；；
(3) it will be sub-packed in ampoule after liquid aseptic filtration；
After (4) 100 DEG C of flowing steam sterilization 15min to obtain the final product；
In the injection, dexamethasone sodium phosphate dosage is 20~40mg/ml, more preferable 30mg/ml；
The antioxidant is sodium hydrogensulfite；
The stabilizer is propylene glycol；
The pH adjusting agent is sodium hydroxide or hydrochloric acid；
The metal ion chelation agent is EDTA-2NaCa；
The solubilizer include but not limited to PLURONICS F87, polyoxyethylene sorbitan monoleate,HS15, hydroxypropyl-β-cyclodextrin；
The viscosity modifier is glycerine or Sodium Hyaluronate, and gained injection fluid viscosity is 5.37-24.26cP.
2. Decameth as described in claim 1, administering mode is drug administration by injection, and injection site is tympanum
It is interior.
3. Decameth as described in claim 1, which is characterized in that composition is as follows：
Preparation method：
(1) water for injection for taking 80% full dose, dissolves NaHSO successively3, EDTA-2Na, dexamethasone sodium phosphate and hyaluronic acid,
And pH to 8.0 is adjusted, it is settled to full dose；
(2) it will be sub-packed in after medical filtration in 2ml ampoules, conventional logical nitrogen, sealing；
(3) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
4. Decameth as described in claim 1, which is characterized in that composition is as follows：
, preparation method：
(1) sodium dihydrogen phosphate of recipe quantity and disodium hydrogen phosphate are dissolved with water for injection；
(2) weighing the Sodium Hyaluronate of recipe quantity, fully swelling is stirred to dissolve in (1) solution, weighs the supplementary material of recipe quantity
It is dissolved with above-mentioned solvent, is used in combination 30% sodium hydroxide to adjust pH to 8.0, water for injection is settled to full dose；
(3) it will be sub-packed in after medical filtration in 2ml ampoules, conventional logical nitrogen, sealing；
(4) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
5. Decameth as described in claim 1, which is characterized in that composition is as follows：
Preparation method：
(1) weighing the Sodium Hyaluronate of recipe quantity, fully swelling is stirred to dissolve in appropriate water for injection；
(2) supplementary material for weighing recipe quantity is dissolved with above-mentioned solvent, and 30% sodium hydroxide is used in combination to adjust pH to 8.0, water for injection
It is settled to full dose；
(3) it will be sub-packed in after medical filtration in 2ml ampoules, conventional logical nitrogen, sealing；
(4) it sterilizes：100 DEG C of flowing steam sterilizations, 15min.
6. Decameth as described in claim 1, which is characterized in that composition is as follows：
Preparation method：
(1) water for injection for taking 80% full dose, dissolves NaHSO successively3, EDTA-2Na, dexamethasone sodium phosphate and hyaluronic acid,
Mannitol, and pH to 8.0 is adjusted, it is settled to full dose；
(2) it will be sub-packed in after medical filtration in 5ml in borosilicate glass tube vial, partly jump a queue, be lyophilized, freeze-drying terminates to pour nitrogen, Quan Jia
Plug pricks aluminium lid, obtains lyophilized preparation.
7. Decameth as described in claim 1, which is characterized in that composition is as follows：
, preparation method：
(1) sodium dihydrogen phosphate of recipe quantity and disodium hydrogen phosphate are dissolved with water for injection；
(2) weighing the Sodium Hyaluronate of recipe quantity, fully swelling is stirred to dissolve in (1) solution, weighs the supplementary material of recipe quantity
It is dissolved with above-mentioned solvent, is used in combination 30% sodium hydroxide to adjust pH to 8.0, water for injection is settled to full dose；
(3) it will be sub-packed in after medical filtration in 5ml in borosilicate glass tube vial, partly jump a queue, be lyophilized, freeze-drying terminates to pour nitrogen, Quan Jia
Plug pricks aluminium lid, obtains lyophilized preparation.
8. Decameth as described in claim 1, which is characterized in that composition is as follows：
Preparation method：
(1) weighing the Sodium Hyaluronate of recipe quantity, fully swelling is stirred to dissolve in appropriate water for injection；
(2) supplementary material for weighing recipe quantity is dissolved with above-mentioned solvent, and 30% sodium hydroxide is used in combination to adjust pH to 8.0, water for injection
It is settled to full dose；
(3) it will be sub-packed in after medical filtration in 5ml in borosilicate glass tube vial, partly jump a queue, be lyophilized, freeze-drying terminates to pour nitrogen, Quan Jia
Plug pricks aluminium lid, obtains lyophilized preparation.
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|---|---|---|---|
| CN201810486524.4A CN108403628B (en) | 2018-05-21 | 2018-05-21 | Dexamethasone sodium phosphate injection |
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|---|---|---|---|
| CN201810486524.4A CN108403628B (en) | 2018-05-21 | 2018-05-21 | Dexamethasone sodium phosphate injection |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109602701A (en) * | 2019-02-22 | 2019-04-12 | 湖北九州通中加医药有限公司 | A kind of dexamethasone sodium phosphate injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109602701A (en) * | 2019-02-22 | 2019-04-12 | 湖北九州通中加医药有限公司 | A kind of dexamethasone sodium phosphate injection and preparation method thereof |
| CN111773187A (en) * | 2020-06-15 | 2020-10-16 | 北京和舆医药科技有限公司 | Dexamethasone sodium phosphate freeze-dried powder injection |
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| CN112516091B (en) * | 2020-06-15 | 2022-03-29 | 和舆(苏州)医药科技有限公司 | Dexamethasone sodium phosphate freeze-dried powder injection |
| CN111773187B (en) * | 2020-06-15 | 2022-08-19 | 和舆(苏州)医药科技有限公司 | Dexamethasone sodium phosphate freeze-dried powder injection |
| CN114681411A (en) * | 2022-04-15 | 2022-07-01 | 臻赫医药(杭州)有限公司 | Biological gel preparation, preparation method and application thereof |
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| CN108403628B (en) | 2021-01-08 |
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