CN108403651A - dezocine oral preparation - Google Patents
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- CN108403651A CN108403651A CN201810420839.9A CN201810420839A CN108403651A CN 108403651 A CN108403651 A CN 108403651A CN 201810420839 A CN201810420839 A CN 201810420839A CN 108403651 A CN108403651 A CN 108403651A
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Abstract
The invention discloses a kind of oral preparation of dezocine, the dezocine oral preparation is suitable for unit formulation comprising the auxiliary material of the dezocine of 5mg~150mg and optional pharmaceutically acceptable oral preparation.In addition, the invention also discloses the Preparation method and uses of above-mentioned oral preparation.Clinical test shows that in dosage range, dezocine oral preparation of the invention has similar blood concentration with commercially available dezocine injection, and adverse reaction is slight, and administration is more convenient.
Description
The application be submit on 2 13rd, 2015 application No. is 201510080325.X, entitled " dezocine mouths
The divisional application of formulation " application
Technical field
The invention belongs to technical field of medicine, and in particular to a kind of dezocine oral preparation and the system of said preparation
Preparation Method, and treat the purposes of pain.
Background technology
Dezocine (Dezocine), its chemical name is：13- amino -5,6,7,8,9,10,11,12- octahydro -5- methyl -
5,11- methylene benzo cyclodecene -3- alcohol.CAS:53648-55-8.
Structural formula is as follows：
Dezocine is a kind of potent opium kind analgesics, such drug has the effect of agonist and antagonist concurrently, by right
Receptor subtype affinity is different from other opioid drugs and shows different features, and analgesic activity is better than pentazocine,
It is additive smaller, to severe pain and chronic ache, internal organ angina and advanced cancer in being clinically mainly used for after treatment is performed the operation
The pain of patient, analgesia intensity, onset time and acting duration and maximum analgesic effect are suitable with morphine, compare Sauteralgyl
5-9 times strong, side effect is slight, and tolerance is good, only has listed dezocine injection type both at home and abroad at present.
Chinese patent CN104257615A describes a kind of dezocine freeze-drying medicinal composition and preparation method thereof, uses ground
Zuo Xin, cosolvent, excipient, stabilizer and acid-base modifier are configured to solution, after freeze-dried, obtained freeze-dried composition.
Chinese patent CN104224734A describe a kind of dezocine freeze-drying medicinal composition and preparation method thereof by：It helps on ground
It is pungent, freeze-dried excipient, the compositions such as antioxidant, soda acid pH adjusting agent.
The above patent describes only the preparation method of freeze-drying preparation for injection；Relative injection is administered, and it is the most frequently used to take orally
It is also most convenient most economical means, convenient drug administration, without pain, medicine stability is high, can accurately calculate dose.But
Mainly in liver glucuronidation occurs for unstable, the dezocine drug administration by injection that oral preparation absorbs, mainly with glucose alditol
The conjugate form excretion of acid.First pass effect of hepar generates large effect to drug absorption and effect, on the other hand, at present also
Do not have dezocine to take orally the report of adverse reaction, by oral dezocine there may be the adverse reaction different from injection, these
Adverse reaction is needed through suitable dose and prescription, to avoid the generation of adverse reaction.Therefore it is developed according to the prior art a kind of
The oral preparation of dezocine is very difficult.
Invention content
The present inventor is found that a kind of dezocine oral preparation through a large amount of research, realized under doses take orally to
Medicine has simultaneously reached therapeutic effect.
The object of the present invention is to provide a kind of oral preparations of dezocine.
The second object of the present invention is to provide the preparation method of above-mentioned dezocine oral preparation.
Third object of the present invention is to provide the purposes of above-mentioned dezocine oral preparation.
Specifically, the present invention provides a kind of oral preparation of dezocine, the per unit system of the dezocine oral preparation
Agent includes the auxiliary material of the dezocine and optional pharmaceutically acceptable oral preparation of 5mg~150mg.So-called unit formulation refers to
Every in tablet, every of oral administration solution, every bag of granule or every capsule of capsule.
In a kind of preferred embodiment of the present invention, dezocine oral preparation provided by the invention, unit dosage forms are
It is daily to take orally three times, moreover, the dezocine oral preparation includes 5~50mg dezocines and optional pharmaceutically acceptable mouth
The auxiliary material of formulation.
In a kind of preferred embodiment of the present invention, dezocine oral preparation provided by the invention, unit dosage forms are
It is daily oral primary, moreover, the dezocine oral preparation includes 10~100mg dezocines and optionally pharmaceutically acceptable
The auxiliary material of oral preparation.
In embodiments of the invention, dezocine oral preparation provided by the invention, selected from tablet, capsule, granule,
Or the pharmaceutical dosage form that oral administration solution etc. can be administered orally.Here, the tablet includes conventional tablet, sustained release tablets, control
Release the tablet that piece or dispersible tablet etc. can be taken orally；The capsule includes that common capsule and slow-release controlled-release etc. are various
Capsule；The granule is the granule containing sugar or without sugar.
In embodiments of the invention, dezocine oral preparation provided by the invention is preferably tablet, more preferably
For sustained release tablets.
In a preferred embodiment of the invention, dezocine oral preparation provided by the invention is dezocine tablet, wherein
The auxiliary material of the pharmaceutically acceptable oral preparation includes filler, disintegrant, adhesive and lubricant.
In a preferred embodiment of the invention, dezocine oral preparation provided by the invention is dezocine sustained-release tablet,
The auxiliary material of the wherein pharmaceutically acceptable oral preparation includes filler, slow-release material, adhesive and lubricant.
In embodiments of the invention, dezocine oral preparation provided by the invention, wherein the filler is selected from micro-
One or more of crystalline cellulose, lactose, starch, pre-paying starch, mannitol, sorbierite, preferably microcrystalline cellulose.
In embodiments of the invention, dezocine oral preparation provided by the invention, wherein the slow-release material is selected from
One or more of hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, ethyl cellulose, preferably hydroxypropyl methylcellulose.
In embodiments of the invention, dezocine oral preparation provided by the invention, wherein the disintegrant is selected from carboxylic
Methyl starch sodium, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, cross-linked carboxymethyl cellulose are received, in dried starch
One or more.
In embodiments of the invention, dezocine oral preparation provided by the invention, wherein described adhesive hydroxypropyl is fine
Tie up one or more of element, methylcellulose, ethyl cellulose, povidone or crospovidone.
In embodiments of the invention, dezocine oral preparation provided by the invention, wherein the lubricant is tristearin
One or more of sour magnesium, talcum powder, superfine silica gel powder, fumaric acid odium stearate.
Second aspect, the present invention provides the preparation method of above-mentioned dezocine oral preparation, this method include by 5mg~
The dezocine of 150mg is mixed with the auxiliary material of optional pharmaceutically acceptable oral preparation, and is configured to Orally-administrable
Dosage form.
The third aspect, the present invention provides ache above-mentioned dezocine oral preparation to severe in preparing treatment after surgery
It is applied in the drug of pain and chronic pain patient.
Dezocine oral preparation provided by the invention contains the dezocine of specific quantity, by three times per day taking or one day one
It is secondary take can effectively treat operation after in severe pain and chronic ache, not only realize therapeutic effect, while non-toxic
Ill-effect.Dezocine injection compared with the prior art is used for chronic ache, is administered once every 3~6 hours when needing；
The oral dezocine oral preparation of the present invention is by the oral effect for realizing drug administration by injection, moreover, using the sustained release of dezocine
Dosage form is taken once a day for chronic ache.
Description of the drawings
Fig. 1：The Drug-time curve (N=5) of healthy adult subject's single oral different size dezocine sustained release tablets.
Fig. 2：Healthy adult subject takes orally dezocine ordinary tablet or the Drug-time curve of sustained release tablets (10mg) compares (N=5).
Fig. 3：Healthy adult subject takes orally dezocine ordinary tablet or the Drug-time curve of sustained release tablets (15mg) compares (N=5).
Fig. 4：Healthy adult subject takes orally dezocine ordinary tablet or the Drug-time curve of sustained release tablets (20mg) compares (N=5).
Fig. 5：Healthy adult subject takes orally dezocine ordinary tablet or the Drug-time curve of sustained release tablets (25mg) compares (N=5).
Fig. 6：Healthy adult subject takes orally dezocine ordinary tablet or the Drug-time curve of sustained release tablets (30mg) compares (N=5).
Fig. 7：The mode Drug-time curve (N=15) of dezocine (15mg) different dosing in healthy adult subject.
Specific implementation mode
By embodiment in detail below, reader can be helped to be better understood from the present invention, but following example cannot manage
Solution is for limiting the present invention.
Embodiment 1：It is prepared by dezocine oral administration solution
Dezocine oral administration solution
Preparation method：The dezocine raw material after crushing, sieving is weighed, the purified water of above-mentioned recipe quantity is added, lactic acid is adjusted after dissolving
PH value is saved to 3.8, filtration sterilization.
Embodiment 2：It is prepared by dezocine piece
Dezocine tablet recipe：
Preparation method：The dezocine raw material after crushing, sieving is weighed, is formed sediment with the lactose, microcrystalline cellulose, carboxylic first of above-mentioned recipe quantity
Powder sodium mixes, and 10% hydroxypropyl methylcellulose solution is added and is uniformly mixed in right amount, is made suitable softwood, crosses 16 mesh sieve, is made
Grain, 60 DEG C of drying, dry particl cross 20 mesh whole grains, and magnesium stearate is added and is uniformly mixed, tabletting.
Embodiment 3：It is prepared by dezocine sustained release tablets
Dezocine sustained-release tablet recipe：
Preparation method：The dezocine raw material after crushing, sieving is weighed, it is mixed with microcrystalline cellulose, the PVP K30 of above-mentioned recipe quantity
It closes uniformly, adds the mixing of 80% ethanol solutions of 5%PVP, suitable softwood is made, cross 16 mesh sieve, particle, 60 DEG C of bakings are made
Dry, dry particl crosses 18 mesh whole grains, and addition hydroxypropyl methylcellulose (K4M), magnesium stearate are uniformly mixed, and tabletting is coated to obtain the final product.
Embodiment 4:It is prepared by dezocine piece
1, dezocine piece
Prescription：
Preparation method：The dezocine raw material after crushing, sieving is weighed, is formed sediment with the lactose, microcrystalline cellulose, carboxylic first of above-mentioned recipe quantity
Powder sodium mixes, and 10% hydroxypropyl methylcellulose solution is added and is uniformly mixed in right amount, is made suitable softwood, crosses 16 mesh sieve, is made
Grain, 60 DEG C of drying, dry particl cross 20 mesh whole grains, and magnesium stearate is added and is uniformly mixed, tabletting.
Embodiment 5：It is prepared by dezocine sustained release tablets
Dezocine sustained release tablets
Prescription：
Preparation method：The dezocine raw material after crushing, sieving is weighed, it is mixed with microcrystalline cellulose, the PVP K30 of above-mentioned recipe quantity
It closes uniformly, adds the mixing of 80% ethanol solutions of 5%PVP, suitable softwood is made, cross 16 mesh sieve, particle, 60 DEG C of bakings are made
Dry, dry particl crosses 18 mesh whole grains, and addition hydroxypropyl methylcellulose (K4M), magnesium stearate are uniformly mixed, and tabletting is coated to obtain the final product.
Effect example 1：Pharmacodynamic study
The only injection that dezocine lists both at home and abroad, without the report of related oral curative effect, therefore using mouse and greatly
Mouse comparison use after dezocine and morphine on heat radiation and hot plate induced pain influence as judge dezocine take orally whether effectively according to
According to.
Test medicine：Such as the dezocine oral administration solution of embodiment 1
Positive drug：Morphine hydrochloride injection
Administering mode：Normal saline dilution dezocine oral administration solution and morphine hydrochloride injection, gastric infusion is respectively adopted.
Administered volume：10ml/kg.
Influence of the dezocine to mouse heat radiation induced pain
Method：Female ICR mice, gastric infusion dezocine 5,10,20,40mg/kg, morphine 40mg/kg, control are given same
ML normal saline.Thermotropic pain instrument is used up after twenty minutes measures mouse induced pain incubation period.
Table 1：On the preclinical influence of photo-thermal induced pain after intragastric administration on mice dezocine
Data are average value ± SD, n=10 in table.*P<0.05, * * p<0.01, * * * p<0.001
As a result：When intragastric administration on mice gives 10,20 and 40mg/kg of dezocine, mouse tail pain caused by photo-thermal can be obviously prolonged
Incubation period.ED50 is 5.9mg/kg, ED95 9.9mg/kg.40mg/kg morphines also have and prolong well under the experiment condition
The effect of long flick latency.
Influence of the dezocine to mouse hot-plate induced pain
Method：Male ICR mouse is put on 55 DEG C of hot plates, and meter licks the metapedes time i.e. threshold of pain for the first time.It is 20-35 to select the threshold of pain
Second mouse, consubstantiality is given in gastric infusion dezocine after 5 hours (10,40,100mg/kg) or morphine (100mg/kg), control
Product physiological saline.It is put in after twenty minutes on 55 DEG C of hot plates, meter licks the metapedes time for the first time.
Table 2：Intragastric administration on mice dezocine licks the preclinical influence of foot to hot plate cause
Data are average value ± SD, * * * P in table<0.001
As a result：When intragastric administration on mice gives 10,40 and 100mg/kg of dezocine, mouse can be obviously prolonged and lick sufficient incubation period.
ED50 is 9.4mg/kg, ED95 23.0mg/kg.100mg/kg morphines also have to extend well and hide under the experiment condition
The effect of phase.
Influence of the dezocine to rat heat radiation induced pain
Method：Male Wistar Rats, fasting 12 hours, gastric infusion dezocine (1.25,2.5,5.0,10.0,20.0,
40.0mg/kg) or same volume physiological saline is given in morphine (5.0,10.0mg/kg), control.Thermotropic pain instrument is used up after twenty minutes
Measure rat induced pain incubation period.
Table 3：On the preclinical influence of photo-thermal induced pain after rat oral gavage dezocine
Table Middle latency data are average value ± SD, * * p<0.01, * * * p<0.001
As a result：Refer to table 3.When rat oral gavage gives dezocine more than 2.5mg/kg dosage, photo-thermal can be obviously prolonged and caused
Big rat-tail pain incubation period.ED50 is 1.5mg/kg, ED95 1.9mg/kg.Rat, which gives 10mg/kg morphines also, to be had very well
The preclinical effect of extension.
Conclusion：Experimental result is shown, in mouse heat radiation induced pain, mouse hot-plate induced pain and rat heat radiation induced pain model
In, the ED50 values for taking orally dezocine are respectively 5.9,9.4 and 1.5mg/kg.The throe effect of dezocine is stronger under Isodose.
Effect example 2：Health volunteer's single oral dezocine ordinary tablet tolerance studies
Experimental design：
30 healthy adult subjects are randomly divided into 6 groups according to weight, and every group of 5 people give the ground described in embodiment 2,4
Help pungent conventional tablet, dosage is respectively 5,10,15,20,25,30mg.Empty stomach warm water delivery service from morning, single administration.
It is carried out according to the principle of dosage from low to high, for security consideration, carries out 1 group of research daily, it is previous confirming
After group drug administration safety, next group of research can be just carried out.If 1 serious adverse events or generation occur for previous dosage group
Number of cases >=50% item of moderate and the above adverse events tests termination, no longer carries out subsequent dose experiment.
As a result：
The main pharmacokinetic parameter that healthy adult subject takes orally various dose dezocine ordinary tablet is shown in Table 1.It is tested
Person takes orally 5-30mg dezocines, and dezocine absorbs very rapid, TmaxFor 1.0-1.2h, slower t is eliminated in vivo1/2For
3.7-4.1h.With the increase of dosage, CmaxIt linearly increases, sees Fig. 1.Within the scope of 5-30mg, subject's safety and energy
Tolerance, it is light moderate to test the adverse events occurred in the process.Adverse events increase with dosage, occurrence frequency and journey
Degree is also corresponding to be increased.Mainly adverse events are：Nausea and vomiting, dizziness, perspiration etc..
Table 4：Healthy adult subject takes orally the main pharmacokinetic parameter (N=5) of various dose dezocine ordinary tablet
Effect example 3：Health volunteer's single：Oral dezocine sustained release tablets tolerance studies
Experimental design：
25 healthy adult subjects are randomly divided into 5 groups according to weight, and every group of 5 people give the embodiment of the present application 3 respectively
With 5 dezocine sustained release tablets, dosage is respectively 10,15,20,25mg, 30mg, empty stomach warm water delivery service from morning, single administration.
It is carried out according to the principle of dosage from low to high, for security consideration, carries out 1 group of research daily, it is previous confirming
After group drug administration safety, next group of research can be just carried out.If 1 serious adverse events or generation occur for previous dosage group
Number of cases >=50% item of moderate and the above adverse events tests termination, no longer carries out subsequent dose experiment.
As a result：
Healthy adult subject takes orally various dose dezocine sustained release tablets main pharmacokinetic parameter and is shown in Table 2.Subject
Oral 10-30mg dezocine sustained release tablets, absorb compared with ordinary tablet and obviously slow down, TmaxFor 2.6-2.8h, eliminate in vivo also notable
Slow down, t1/2For 5.7-5.9h.With the increase of dosage, CmaxIt linearly increases.Within the scope of 10-30mg, subject pacifies
It entirely and is resistant to, it is light moderate to test the adverse events occurred in the process.Adverse events increase with dosage, and frequency occurs
Rate and degree also increase.Mainly adverse events are：Nausea and vomiting, dizziness, perspiration etc..
Compared with the conventional tablet with dosage, dezocine sustained release tablets t1/2And TmaxSignificantly extend, CmaxThough slightly reduce,
It is that variation is little, shows apparent slow release characteristic, see Fig. 2~6.
Table 5：Healthy adult subject takes orally the main pharmacokinetic parameter (N=5) of various dose dezocine sustained release tablets
Effect example 4：The pharmacokinetics of dezocine (15mg) different modes of administration compares in health volunteer
Experimental design：
15 adult healthy subjects, are randomly divided into 3 groups, are designed using double 3 × 3 latin square experiment of 3 period of 3 preparation.
One group of sequence medication by injection dezocine 15mg, oral conventional tablet (15mg) and oral sustained release piece (15mg)；Two groups are pressed mouth
Take the sequence medication of sustained release tablets (15mg), injection dezocine 15mg and oral conventional tablet (15mg)；Three groups by oral ordinary tablet
The sequence medication of agent (15mg), oral sustained release piece (15mg) and injection dezocine 15mg；The cleaning phase is one week.
As a result
The main pharmacokinetic parameter of dezocine (15mg) different modes of administration is shown in Table 3 in healthy adult subject.Mouthful
Take 15mg dezocines ordinary tablet and the C of sustained release tabletsmaxRespectively 15.8 ± 3.2 and 13.9 ± 2.9ng/ml；Oral 15mg dezocines
The T of ordinary tablet and sustained release tabletsmaxRespectively 1.1 ± 0.3 and 2.7 ± 0.7h；Inject 15mg dezocines and oral 15mg dezocines
The t of ordinary tablet or sustained release tablets1/2Respectively 2.7 ± 0.8,3.8 ± 1.4 and 5.7 ± 2.1h；It injects 15mg dezocines and takes orally
The AUC of 15mg dezocines ordinary tablet or sustained release tablets0-16hRespectively 85.6 ± 9.4,54.1 ± 6.1 and 54.1 ± 6.1ugh/L,
Dezocine ordinary tablet and the absolute bioavailability of sustained release tablets are respectively 63.20% and 65.40%, see Fig. 7.Adverse events：Note
The adverse events that administration occurs are penetrated to be nauseous (2/15), vomit (1/15), dizzy (1/15)；Oral conventional tablet occurs bad
Event is dizzy (1/15)；Oral sustained release piece occurs without adverse events.Compared to drug administration by injection, oral dezocine does not generate gastrointestinal tract
Adverse reaction, other adverse reactions are also smaller than injection.
Table 6：Main pharmacokinetic parameter (the N=of dezocine (15mg) different modes of administration in healthy adult subject
15)
Claims (9)
1. a kind of dezocine oral preparation, unit formulation includes the dezocine of 1mg~150mg and can pharmaceutically connect optionally
The auxiliary material for the oral preparation received；Preferably, 5~100mg containing dezocine in the unit dosage forms of the dezocine oral preparation, it is more excellent
Selection of land, 5~50mg containing dezocine in the unit dosage forms of the dezocine oral preparation.
2. dezocine oral preparation as described in claim 1, the dosage form of the oral preparation be selected from tablet, capsule, granule,
Or oral administration solution, preferably conventional tablet or sustained-release tablet.
3. dezocine oral preparation as claimed in claim 2, wherein the dezocine oral preparation is dezocine tablet,
It is daily to take orally three times.
4. dezocine oral preparation as claimed in claim 2, wherein the dezocine oral preparation is sustained for dezocine
Piece, it is daily oral primary.
5. dezocine oral preparation as claimed in claim 2, wherein the dezocine oral preparation is that dezocine is common
The auxiliary material of piece, pharmaceutically acceptable oral preparation therein includes filler, disintegrant, adhesive and lubricant；
Preferably, the filler in microcrystalline cellulose, lactose, starch, pre-paying starch, mannitol, sorbierite one
Kind or several, more preferable microcrystalline cellulose；
The disintegrant is selected from sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross linked polyvinyl pyrrolidone, crosslinking carboxylic first
One or more of Ji Xianweisuna, dried starch；
One kind or several in described adhesive hydroxypropylcellulose, methylcellulose, ethyl cellulose, povidone or crospovidone
Kind；
The lubricant is one or more of magnesium stearate, talcum powder, superfine silica gel powder, fumaric acid odium stearate.
6. dezocine oral preparation as claimed in claim 2, wherein the dezocine oral preparation is sustained for dezocine
The auxiliary material of piece, pharmaceutically acceptable oral preparation therein includes filler, slow-release material, adhesive and lubricant；
Preferably, the filler in microcrystalline cellulose, lactose, starch, pre-paying starch, mannitol, sorbierite one
Kind or several, more preferable microcrystalline cellulose；
One kind or several in described adhesive hydroxypropylcellulose, methylcellulose, ethyl cellulose, povidone or crospovidone
Kind；
The lubricant is one or more of magnesium stearate, talcum powder, superfine silica gel powder, fumaric acid odium stearate；
The one kind or several of the slow-release material in hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, ethyl cellulose
Kind, more preferable hydroxypropyl methylcellulose.
7. dezocine oral preparation as claimed in claim 5, wherein the dezocine oral preparation is that dezocine is common
Piece, component and content are：
Alternatively,
8. dezocine oral preparation as claimed in claim 6, wherein the dezocine oral preparation is sustained for dezocine
Piece, component and content are：
Alternatively,
9. purposes of any one of the claim 1-8 dezocine oral preparations in preparing the drug for treating pain.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810420839.9A CN108403651A (en) | 2015-02-13 | 2015-02-13 | dezocine oral preparation |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810420839.9A CN108403651A (en) | 2015-02-13 | 2015-02-13 | dezocine oral preparation |
| CN201510080325.XA CN104622791A (en) | 2015-02-13 | 2015-02-13 | Dezocine oral preparation |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510080325.XA Division CN104622791A (en) | 2015-02-13 | 2015-02-13 | Dezocine oral preparation |
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| CN108403651A true CN108403651A (en) | 2018-08-17 |
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| CN201810420839.9A Pending CN108403651A (en) | 2015-02-13 | 2015-02-13 | dezocine oral preparation |
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| CN111606816A (en) * | 2017-05-22 | 2020-09-01 | 扬子江药业集团有限公司 | Dezocine crystal form and preparation method thereof |
| CN108653446B (en) * | 2018-07-26 | 2019-05-28 | 四川大学华西医院 | A kind of surface anesthesia pharmaceutical composition, micro emulsion and its preparation method and application |
| CN111939145A (en) * | 2020-07-23 | 2020-11-17 | 深圳大学 | Application of dezocine in preparation of nicotinamide phosphoribosyltransferase inhibitor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1741790A (en) * | 2003-01-23 | 2006-03-01 | 株式会社太平洋 | Sustained-release preparations and method for producing the same |
| CN101578094A (en) * | 2006-10-10 | 2009-11-11 | 潘威斯脱药物公司 | Robust sustained release formulations of oxymorphone and methods of use thereof |
| CN101578096A (en) * | 2006-10-10 | 2009-11-11 | 潘威斯脱药物公司 | Robust sustained release formulations |
| CN104257615A (en) * | 2014-09-15 | 2015-01-07 | 扬子江药业集团有限公司 | Dezocine freeze-dried pharmaceutical composition and preparation method thereof |
-
2015
- 2015-02-13 CN CN201510080325.XA patent/CN104622791A/en active Pending
- 2015-02-13 CN CN201810420839.9A patent/CN108403651A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1741790A (en) * | 2003-01-23 | 2006-03-01 | 株式会社太平洋 | Sustained-release preparations and method for producing the same |
| CN101578094A (en) * | 2006-10-10 | 2009-11-11 | 潘威斯脱药物公司 | Robust sustained release formulations of oxymorphone and methods of use thereof |
| CN101578096A (en) * | 2006-10-10 | 2009-11-11 | 潘威斯脱药物公司 | Robust sustained release formulations |
| CN104257615A (en) * | 2014-09-15 | 2015-01-07 | 扬子江药业集团有限公司 | Dezocine freeze-dried pharmaceutical composition and preparation method thereof |
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| CN104622791A (en) | 2015-05-20 |
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