CN105963253A - Rotigotine long-acting waterborne suspension type injection - Google Patents
Rotigotine long-acting waterborne suspension type injection Download PDFInfo
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- CN105963253A CN105963253A CN201610434463.8A CN201610434463A CN105963253A CN 105963253 A CN105963253 A CN 105963253A CN 201610434463 A CN201610434463 A CN 201610434463A CN 105963253 A CN105963253 A CN 105963253A
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- rotigotine
- injection
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- suspension
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K47/26—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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Abstract
The invention relates to a long-acting waterborne suspension type injection with rotigotine as a main component. According to the injection, rotigotine is made to form a medicine inventory in an intramuscular injection or subcutaneous injection mode, so that the rotigotine is slowly released, the long-acting effect is achieved, and the effect can be maintained for 14 days or longer. According to the suspension type injection, no slow-release auxiliary material is adopted, and slow and stable release is achieved by controlling the average grain diameter of medicine. In this way, the content of rotigotine can be effectively increased, and the medicine effect of rotigotine can be prolonged to the maximum extent. The invention further provides a preparation method of the injection.
Description
Technical field
The present invention relates to long-acting aqueous suspension type injection that a kind of main constituent is rotigotine and preparation method thereof.
Background technology
Rotigotine is a kind of dopamine-receptor stimulant, can be used for treatment early stage and the parkinson disease of progressive stage, its English name
For Rotigotine, structure is as follows:
Rotigotine is extremely low due to oral administration biaavailability, is therefore not suitable for being prepared as oral formulations, and sieve the most listed replaces
Dagger-axe spit of fland preparation is transdermal patch (trade name).Due to the half-life of rotigotine shorter (the most several hours),
Therefore its preparation capable of permeating skin needs frequent drug administration, it is impossible to the problem efficiently solving patient's compliance.
The injection that rotigotine is prepared as stock's type can make medicine blood drug level of long-term held stationary in human body, this
Individual dosage form is the most also to improve the effective ways of patient's compliance owing to need not frequent drug administration.Patent CN1531428A discloses
Stock's type injection of a kind of rotigotine, the feature of said preparation is that the low fat-soluble pharmaceutical salts of rotigotine is mixed in oil
Making long-acting injection type in property solution, therefore this dosage form is oleaginous suspension.This patent is not to this oily suspensions
Concrete composition carries out disclosure, and it is delayed by concrete particle diameter and the size controlling technique thereof etc. that the most do not comprise this rotigotine pharmaceutical salts
Release effect and produce the content of material impact.
Patent CN1762495A discloses a kind of stock's type preparation comprising dopamine receptor class medicine, and these dopamine are subject to
Body class medicine includes derivant and the pharmaceutical salts thereof of rotigotine.The dosage form of this patent relates to injectable microsphere, injection gel
And implant.The preparation that this patent relates to comprises the pharmaceutically acceptable polymer adjuvant of larger proportion, and these pharmaceutically acceptable polymers are used for controlling
Drug release processed, in the preparation that this patent relates to, the ratio of pharmaceutic adjuvant and active drug is more than 1:1.Stock's type long-acting injection
Typically by maintaining long-term drug effect at the medicine of muscle or subcutaneous injection larger dose, and these injection systems determine
The injection capacity of preparation is relatively low (generally less than 5ml), and therefore long-acting injection must be use up on the premise of limited injection capacity
Amount improves drug loading.But, the long-acting injection utilizing high molecular slow-release adjuvant to realize slow release effect (includes micropill injection
And the dosage form such as gel injection) owing to containing the high polymer adjuvant of larger proportion in prescription, the most such dosage form is (the most special
Profit dosage form described by CN1762495A) must be significantly to reduce the active drug in preparation as cost.Additionally, high-load
High polymer adjuvant also can increase the weight of human body metabolism burden.This is one of the disadvantage of durative action preparation of the type.
In order to solve the problems referred to above, this patent provides the injection of the long-acting suspension type with aqueous solution as carrier of a kind of innovation
Agent.The active drug that the long-acting injection of the present invention uses is rotigotine rather than its pharmaceutical salts, and this dosage form utilizes sieve to replace dagger-axe
The extremely low water solublity in spit of fland is prepared into being scattered in the suspension of aqueous carrier；This suspension can pass through muscle or subcutaneous note
The mode penetrated is administered, and discharges concentration and reaches the medicine of effective treatment level, and this effect can maintain to 14 days or longer
Time.The slow release effect of the durative action preparation of the present invention can be realized by the particle diameter and drug loading that control rotigotine, is independent of
In high molecular polymer adjuvant, therefore the preparation of the present invention can improve drug loading to greatest extent, thus reduces injection capacity.
Summary of the invention
The invention provides a kind of for muscle or hypodermic rotigotine long-acting aqueous stock's type injection.Water
Property injection refer to this injection using aqueous solution as the carrier of injection, stock's type refers to that the active substance of this injection is at note
In internal formation medicine stock after penetrating.The drug reservoir of the present invention saves as rotigotine granule, and this stock discharges concentration and reaches
The effectively medicine for the treatment of level, this effect is able to maintain that 14 days or longer time.
The rotigotine long-acting injection that the present invention relates to is suspension when injection, and this suspension can pass through two ways
Obtain: (1) preserves with the form of liquid suspension；It is used directly for drug administration by injection with the preparation that this form preserves；(2) with
Dried powder and diluent two parts preserve respectively, and during drug administration by injection, two parts are mixed to form suspension.
The rotigotine long-acting injection of the present invention, in addition to including effective substance rotigotine, it is also possible to comprises following
Adjuvant:
1) surface stabilizer of one or more than one
2) suspending agent of one or more than one
3) pH adjusting agent of one or more than one
4) one or more than one osmotic pressure regulator
5) chelating agen of one or more than one
6) a kind of or a kind of antioxidant or preservative
Suspending agent therein, pH adjusting agent, osmotic pressure regulator, chelating agen, antioxidant or preservative alternative are added,
Therefore can also be without, the selection of these adjuvants is not any limitation as by this patent.
The long-acting injection of the present invention does not comprise slow-release auxiliary material, and therefore the topmost influence factor of drug release is working substance
The granular size of matter.The size of the active substance granule of said preparation can be controlled by multiple method, on the one hand, Ke Yitong
The grain diameter control method crossing from top to bottom (Top-down) realizes, and these methods include wet grinding, high pressure homogenize (High
Pressure Homogenization), microjet homogenizing (Microfluidization), comminution by gas stream and ball-milling method etc..Separately
On the one hand, can be realized by the method for (Bottom-up) from the bottom to top, as by controlling the parameter in crude drug crystallization processes
Obtain the granule meeting Particle size requirements.Although inventor finds can be obtained by method from the bottom to top to meet Particle size requirements
Granule, but there is the problem of poor repeatability, and different batches grain diameter numerical value difference is relatively big, is extremely difficult to good controlled
Property.And process repeatability and controllability from top to bottom is preferable.Therefore the preparation method that the present invention relates to is by under upper
Method.
The preparation method of from top to bottom (Top-down) of this patent, is after obtaining rotigotine crude drug granule,
The method utilizing grinding, homogenizing or pulverizing carries out, to crude drug, the process that particle diameter reduces, the most smart the step for of utilization
Really control crude drug grain diameter, reached the quality controllability produced by such mode.The side of this size controlling
Formula includes wet treatment and two kinds of approach of dry process, describes in detail individually below.
Wet treatment:
The approach of wet treatment is by using grinding-material that crude drug is ground reaching the purpose of size controlling.At wet method
A kind of mode of reason is to utilize the method ground to be reduced by diameter of aspirin particle, and effective embodiment (such as grinds for utilizing abrasive media
Mill pearl) under conditions of aqueous liquid dispersion, medicine is ground.The another way of wet treatment is to utilize high pressure homogenize
Technology reduces the particle diameter of medicine.Homogeneous technology is including, but not limited to high pressure homogenize and microjet homogenizing.Inventor finds to utilize
The method ground can be efficiently treated through (more than 20%) under higher suspension concentration, and therefore the present invention selects grinding
Mode carries out wet treatment.
During wet treatment, grinding bead particle diameter is less than 3mm, and more excellent is that optimum is less than 1mm less than 2mm.The material of grinding bead
Optional rustless steel, aluminium oxide, titanium oxide and zirconium oxide etc., wherein preferential oxidation zirconium.
It is used directly for injection by the suspension of wet treatment.If but pursued higher preparation stability, permissible
Rotigotine suspension through wet treatment is further dried, is preserved with the form of dried powder.This dried powder exists
Need to add diluent during injection and be deployed into suspension.According to the adjunct ingredient of dried powder, its corresponding diluent can
To be the solution containing adjuvant or the water for injection not comprising any adjuvant.The professional and technical personnel being familiar with this field can
To select drying means according to concrete product quality and production requirement, this patent no longer describes in detail.Being dried of suspension can be led to
Crossing various ways to carry out, these modes are including, but not limited to lyophilization and spray drying, and the present invention is not to dry part
It is described in detail, does not limits whether being dried.
Dry process:
The mode of dry process is for pulverize rotigotine crude drug the most under the dry condition.For dry process,
Inventor finds that comminution by gas stream (Air jet milling) and ball-milling method (Ball milling) all can efficiently control sieve for dagger-axe
Spit of fland particle diameter.Inventor finds by above-mentioned dry processing method simultaneously, also can be preferable in the case of being added without any adjuvant
Complete the control of rotigotine particle diameter.In view of crude drug stability in the case of individually encapsulation is more preferable, therefore inventor exists
Preferably directly rotigotine crude drug is pulverized in dry process.Inventor simultaneously it has been investigated that, though by ball-milling method
So can reach the requirement of particle diameter, but due to grinding bead and grind cavity friction and can produce chip in ball-milling method, these chips
More difficult removing, and preferable through the rotigotine particle size distribution uniformity of comminution by gas stream process, and also chip is few, therefore exists
The mode of preferred comminution by gas stream in dry process.Powder after dry process can directly preserve in packaging material in fill.Bag
The powder of dress needs to form suspension rear injectable with after the diluent mixing being further provided with before the injection.Dilute in the present invention
Release liquid and be equipped with method for be mixed according to ratio water for injection by each adjuvant.
Due to the hydrophobicity of active drug, in order to keep the stability of suspension, the rotigotine long-acting injection of the present invention
Agent must comprise the surface stabilizer of one or more than one.Surface stabilizer includes some heavy polymer, low
Polydispersity polymer and surfactant；Wherein surfactant include nonionic, ion, anion, cation and both sexes from
Subtype surfactant.Inventor finds that the hydrophobicity of rotigotine is relatively strong, and adding surfactant when wet treatment can
Effectively to strengthen the suspension ability of rotigotine granule, allow its applicable wet grinding.Therefore, for the preparation technology of wet treatment,
Surface stabilizer adds before the milling, for improving the surface activity of granule.For the preparation technology of dry process, surface-stable
Agent has only to join in diluent.Surface stabilizer can be the surfactant of ion-type or nonionic, and it includes
But it is not limited to: hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxymethyl cellulose, ethyl cellulose, polyvidone, deoxidation
Sodium cholate, polyvinylpyrrolidone, polysorbate, poloxamer etc..The optional one of surface stabilizer, it is also possible to be two kinds
Or it is two or more.The preferred polysorbate of surface stabilizer (tween) 20 or 80, more preferably polysorbate20.Table
The concentration of face stabilizer is preferably 0.01% to 20%, and more preferably 0.02% to 10%, most preferably 0.1% to 1.5%.?
Process of lapping can add other adjuvant, it is also possible to without.Inventor finds other adjuvants final granule to grinding
Size has a certain impact, but this impact is the most notable.
Can be containing the suspending agent of one or more than one in the rotigotine long-acting injection of the present invention.Suspending agent includes
But it is not limited to Polyethylene Glycol (PEG), carbomer, hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose (CMC) and salt thereof
(such as sodium carboxymethyl cellulose), hyaluronate sodium etc..Wherein preferably carboxymethyl cellulose or sodium carboxymethyl cellulose.Suspending agent
Concentration be preferably 0.01% to 20%, more preferably 0.02% to 10%, most preferably 0.2% to 0.8%.
The rotigotine long-acting injection of the present invention can comprise one or two kinds of, the most two or more pH regulator
Agent, selectable pH adjusting agent including, but not limited to disodium hydrogen phosphate, sodium hydroxide, sodium dihydrogen phosphate, hydrochloric acid, maleic acid,
Tartaric acid, sodium bicarbonate, dibastic sodium phosphate, sodium citrate, acetic acid, lactic acid.Preferably pH regulator value is 5-9, more excellent for 6-8,
It is optimized for 6.5-7.5.
The rotigotine long-acting injection of the present invention can comprise one or two kinds of, and the most two or more osmotic pressuries is adjusted
Joint agent, selectable osmotic pressure regulator can including but not limited to sodium chloride, mannitol, glucose, sorbitol, glycerol,
Polyethylene Glycol, propylene glycol etc., wherein preferred mannitol.
The rotigotine long-acting injection of the present invention can comprise one or two kinds of, the most two or more chelating agen,
Chelating agen can not also be comprised.Select chelating agen including, but not limited to ethylenediaminetetraacetic acid, citric acid, lactic acid, malic acid,
A kind of or above mixture in tartaric acid, disodiumedetate, sodium versenate.
The rotigotine long-acting injection of the present invention can comprise one or two kinds of, the most two or more preservative,
Can also be without preservative.Selective preservative is about including, but not limited to methyl parahydroxybenzoate, preferred concentration
0.18%；Phenol, preferred concentration is about 0.5%；Benzyl alcohol, preferred concentration is about 2%.
Rotigotine granular size has extremely crucial impact to the release of medicine.In order to reach long lasting benefits, this
Rotigotine mean particle size preferably 50 nanometer in bright rotigotine long-acting injection is to 200 microns, and more excellent is 500 to receive
Rice is to 100 microns, and optimum is 1 micron to 50 microns.
For maintenance effective blood drug concentration to two weeks, the drug effect of even more than two weeks, the mean particle size of rotigotine
For preferably 0.5 to 25 micron, more excellent it is 1 to 10 micron, optimally from about 3 microns.
Its active drug concentration of the rotigotine long-acting injection of the present invention is according to suspension during injection by weight
Being 1% to 40%, more excellent is 5% to 30%, and optimum is 8% to 20%.
Accompanying drawing explanation
The present invention is further described with embodiment below in conjunction with the accompanying drawings.
Fig. 1 is that the rotigotine suspension of the embodiment 1 (A group) through wet treatment and the embodiment 3 (B group) through dry process exists
Drug release experiment result figure in rat body.
Fig. 2 is that the rotigotine suspension of the embodiment 1 (A group) through wet treatment and the embodiment 3 (B group) through dry process exists
Drug release experiment result figure in Beagle dog body.
Detailed description of the invention
Embodiment 1
The present embodiment prepares rotigotine long-acting injection by the way of wet treatment.Detailed description of the invention: weigh 200g and put down
All the rotigotine of particle diameter about 50 microns, mixes it with 15g polysorbas20, and add water 1000ml, continues stirring until suspension uniform.
With wet milk (WAB DYNO MILL MULTI LAB), suspension is ground.After grinding, rotigotine grain diameter is:
D10 between 0.8 to 1.3 micron, D50 between 2.6 to 3.8 microns, D90 is between 8.5 to 12.5 microns.
1000ml diluent is prepared further accordance with following table:
| PEG 4000 | 120g |
| Sodium dihydrogen phosphate | 0.8g |
| Citric acid | 2g |
| NaOH or HCl | To pH 7.0 |
| Water for injection | To 1000ml |
Suspension for injection is obtained after the suspension obtained after wet treatment and diluent mixing.
Embodiment 2
The present embodiment prepares rotigotine long-acting injection by the way of wet treatment.Detailed description of the invention: weigh average particle
The rotigotine 200g that footpath is about 50 microns, mixes with the diluent prepared according to following table:
| Tween 80 | 15g |
| Sodium dihydrogen phosphate-water | 0.8mg |
| Sodium carboxymethyl cellulose | 18g |
| Citric acid | 2g |
| NaOH or HCl | To pH 7.0 |
| Water for injection | To 1000ml |
Continue stirring until suspension uniform.The suspension stirred is joined in wet milk and is ground.Milling apparatus and
Grinding condition is same as in Example 1, is ground to stop grinding when rotigotine grain diameter is consistent with embodiment 1.After grinding
Suspension for injection is i.e. obtained after suspension and the mixing of 1000ml water for injection.
Embodiment 3
The present embodiment prepares rotigotine long-acting injection by the method for dry process.Detailed description of the invention: weigh 100g and put down
All the rotigotine of particle diameter about 50 microns, utilizes the mode of comminution by gas stream to reduce diameter of aspirin particle, and disintegrating apparatus is DEC MC2 air-flow
Pulverizer, after pulverizing, rotigotine particle diameter meets the particle size range of embodiment 1.According to following table configuration diluent:
| Tween 80 | 10g |
| Sodium dihydrogen phosphate-water | 0.4mg |
| Sodium carboxymethyl cellulose | 9g |
| Mannitol | 4g |
| NaOH or HCl | To pH 7.0 |
| Water for injection | To 1000ml |
Suspension for injection is i.e. obtained after powder after comminution by gas stream and diluent being sufficiently mixed.
Embodiment 4
The present embodiment method configuration rotigotine long-acting injection by dry process.Detailed description of the invention: weigh 100g and put down
All the rotigotine of particle diameter about 50 microns, utilizes the mode of comminution by gas stream to reduce diameter of aspirin particle, disintegrating apparatus and embodiment 3 phase
With, after pulverizing, particle diameter rotigotine particle diameter meets the particle size range of embodiment 1.According to following table configuration diluent:
| Polysorbas20 | 9g |
| Sodium dihydrogen phosphate-water | 0.4mg |
| Carboxymethyl cellulose | 10g |
| Citric acid | 1.8g |
| NaOH or HCl | To pH 7.0 |
| Water for injection | To 1000ml |
Suspension for injection is i.e. obtained after powder after comminution by gas stream and diluent being sufficiently mixed.
Embodiment 5
This embodiment is preparation long lasting benefits checking example in rat body.Detailed description of the invention: 12 rats are divided into A, B
Group, often group 6.Wherein A group is injected through the rotigotine suspension of embodiment 1 preparation, and dosage is calculated as with rotigotine
20mg/kg.B group injects the same dose of rotigotine suspension prepared by embodiment 3.In be administered before and administration after the 1st,
2, within 3,5,7,8,9,10,11,12,13,14,18 and 21 days, take blood and measure blood drug level.Sample utilizes heparin sodium anticoagulant, warp
3500rpm takes blood plasma detection after being centrifuged 10 minutes.
Blood drug level detection method: utilize LS-MS/MS to detect, internal standard substance is (s)-5,6,7,8-tetrahydrochysene-6-[propyl group
[4-fluorobenzene ethyl] amino]-1-naphthalenol hydrochloride.
Chromatographic condition: liquid-phase chromatographic column is C18 post, particle diameter 5 μm, flowing be methanol mutually: water (0.01mM ammonium acetate and
0.05% glacial acetic acid)=7:3, column temperature is 37 DEG C, and flow velocity is 0.2ml/min, and sample size is 20 μ l.
Mass Spectrometry Conditions: ion source is electro-spray ionization source, 5000V ion injection electric, positive ion mode detects, temperature
Being 350 DEG C, scan mode is selective response detection, and collision energy is 25ev, and rotigotine ion pair is 316/147.1, internal standard
Thing ion pair is 328.1/147.1.Mean blood plasma concentration testing result is shown in Fig. 1.
The rat drug disposition release experiment result of Fig. 1 shows the embodiment 1 through wet treatment and the reality through dry process
Executing the rotigotine suspension of example 3 can keep higher blood drug level to 21 days after injection.This result proves this patent
Rotigotine long-acting injection has obvious long lasting benefits.
Embodiment 6
This embodiment is preparation long lasting benefits checking example in Beagle dog body.Detailed description of the invention: male by 12
Beagle dog is divided into A and B two groups, wherein A group every being mixed by the rotigotine of wet treatment by intramuscular injection embodiment 1
Suspension, dosage is calculated as 6mg/kg with rotigotine；B group then inject same dose of embodiment 3 by dry process
Rotigotine suspension.Before administration and within the 1st, 2,3,5,7,8,9,10,11,12,13,14,18 and 21 days, take blood survey after being administered
Amount blood drug level, utilizes the method detection blood drug level in embodiment 5.Mean blood plasma concentration testing result is shown in Fig. 2.The body of Fig. 2
Interior drug release experiment result shows the rotigotine suspendible of the embodiment 1 through wet treatment and the embodiment 3 through dry process
Liquid can keep higher blood drug level to 21 days after injection.This result proves the rotigotine long-acting injection tool of this patent
There is obvious long lasting benefits.
Claims (10)
1. treating a Parkinsonian long-acting injection, its active substance is rotigotine.
2. the rotigotine long-acting injection described in claim 1, it is characterized by rotigotine after injection can at 14 days or
Slowly discharge in the longer time.
3. the rotigotine long-acting injection described in claim 2, its rotigotine can be with the form of crystallization, unformed shape
The mixture of state, hemicrystalline form, half unformed form or above-mentioned form exists.
4. the rotigotine long-acting injection described in claim 3, its rotigotine exists with the particle form of low aqueous solubility.
5. the rotigotine long-acting injection described in claim 4, the mean diameter of its rotigotine granule is 0.5 to 25 micron
Between, more excellent be 1 to 10 micron between, optimally from about 3 microns.
6. the rotigotine long-acting injection described in claim 1, this injection is aqueous suspension when injection；Aqueous suspendible
Liquid refers to that for disperseing the dispersion phase of rotigotine be aqueous solution.
7. the rotigotine long-acting injection described in claim 6, it is characterised in that comprise one or one in its suspension
Above surfactant.
8. the rotigotine long-acting injection described in claim 7, in addition to surfactants, it is also possible to comprise the auxiliary of other
Material；These adjuvants include the suspending agent of one or more than one, the pH adjusting agent of one or more than one, one or
Plant above osmotic pressure regulator, the chelating agen of one or more than one, the preservative of one or more than one.
9. the rotigotine long-acting injection described in claim 7, the content of rotigotine and adjuvant content used in its preparation
Ratio more than 2:1.
10. the rotigotine long-acting injection described in claim 6, this aqueous suspension can be deposited before the injection in two ways
Put: (1) deposits with the form of liquid suspension；(2) deposit with dried powder and diluent two parts, two parts mixing during injection
Forming suspension, wherein dried powder can be the rotigotine powder comprising one or more adjuvants, or do not comprises
The rotigotine powder of any adjuvant, diluent part can be the solution comprising one or more adjuvants, it is also possible to be not
Comprise the water for injection of adjuvant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610434463.8A CN105963253A (en) | 2016-06-19 | 2016-06-19 | Rotigotine long-acting waterborne suspension type injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610434463.8A CN105963253A (en) | 2016-06-19 | 2016-06-19 | Rotigotine long-acting waterborne suspension type injection |
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| Publication Number | Publication Date |
|---|---|
| CN105963253A true CN105963253A (en) | 2016-09-28 |
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| CN201610434463.8A Pending CN105963253A (en) | 2016-06-19 | 2016-06-19 | Rotigotine long-acting waterborne suspension type injection |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018096560A1 (en) * | 2016-11-23 | 2018-05-31 | Cipla Limited | Long acting depot formulation for the continuous dopaminergic stimulation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103249416A (en) * | 2010-10-18 | 2013-08-14 | 大日本住友制药株式会社 | Sustained-release formulation for injection |
| CN103458895A (en) * | 2010-11-25 | 2013-12-18 | 山东绿叶制药有限公司 | Compositions of rotigotine, derivatives thereof, or pharmaceutically acceptable salts of rotigotine or its derivative |
-
2016
- 2016-06-19 CN CN201610434463.8A patent/CN105963253A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103249416A (en) * | 2010-10-18 | 2013-08-14 | 大日本住友制药株式会社 | Sustained-release formulation for injection |
| CN103458895A (en) * | 2010-11-25 | 2013-12-18 | 山东绿叶制药有限公司 | Compositions of rotigotine, derivatives thereof, or pharmaceutically acceptable salts of rotigotine or its derivative |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018096560A1 (en) * | 2016-11-23 | 2018-05-31 | Cipla Limited | Long acting depot formulation for the continuous dopaminergic stimulation |
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Application publication date: 20160928 |