CN104586764A - Intramuscular injection slow release suspension agent containing paliperidone palmitate and preparation method thereof - Google Patents
Intramuscular injection slow release suspension agent containing paliperidone palmitate and preparation method thereof Download PDFInfo
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- CN104586764A CN104586764A CN201510001427.8A CN201510001427A CN104586764A CN 104586764 A CN104586764 A CN 104586764A CN 201510001427 A CN201510001427 A CN 201510001427A CN 104586764 A CN104586764 A CN 104586764A
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- agent
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- risperidone
- sodium
- handkerchief
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Abstract
The invention discloses an intramuscular injection slow release suspension agent containing paliperidone palmitate. The intramuscular injection slow release suspension agent has the characteristics of long acting, long drug delivery interval time and delay of disease recurrence time and the like and is used for emergency treatment and maintenance treatment of schizophrenia of adults. The invention also provides a preparation method simultaneously and belongs to the technical field of medical pharmacy.
Description
Technical field
The present invention relates to a kind of Palmic acid handkerchief risperidone injection, in particular to a kind of intramuscular injection suspensoid and preparation method thereof of Palmic acid handkerchief risperidone, belong to field of pharmaceutical preparations.Described Palmic acid handkerchief risperidone injection can be used for treatment adult's schizophrenia and two-phase manic disorder.
Background technology
Schizophrenia (schizophrenia) is a kind of serious mental sickness, and symptom is that collapse appears in form of thinking and emotional response.It is with the change of basic individual character, the division of thinking, emotion, behavior, and ergasia and environment inharmonious is the modal psychosis of a class of principal character.Schizophrenia is modal one group of psychosis in psychosis, and in population, schizophrenia annual morbidity is between 0.2 ‰ ~ 0.6 ‰.
Clinical common schizophrenia drug, according to pharmacological action, can be divided into typical case and the large class of atypia two usually.Typical antipsychotic drug comprises chlorpromazine, haloperidol etc.; Atypia antipsychotic drug comprises handkerchief risperidone, clozapine, risperidone etc.The affinity of atypical antipsychotic and d2 dopamine receptor is lower, and it is higher with the affinity of 5-hydroxy tryptamine and norepinephrine receptor, its treatment spectrum extensively simultaneously, classical antipsychotic thing is better than to negative symptoms successful, safety is high, side effect is slight, and taking dose is little, drastically increases the compliance of patient.
Handkerchief risperidone is U.S. FDA ratified for schizoid acute stages treated and maintaining treatment a kind of New antipsychotics in 2006, subsequently in Europe and the listing of Asia country variant.Handkerchief risperidone is atypical antipsychotic agents, its active metabolite paliperidone, belonging to the derivant of benzo-isoxazole, disturbing mainly through blocking dopamine, 5-hydroxy tryptamine and adrenoceptor the intracellular signaling of neurotransmitter in patient's brain to play antipsycholic action.The oral administration biaavailability of handkerchief risperidone is 28%, and the combination rate of plasma protein is 74%, and the half-life that end eliminates phase is 23h, and apparent volume of distribution is 487L.The oral rear main untoward reaction of handkerchief risperidone comprises the outer symptom of anxiety, drowsiness, dizzy, constipation and vertebral body etc.
Patent US 4804663, US 5254556, CN 102153552A etc. describes handkerchief risperidone compounds and preparation process thereof in detail.Patent WO2013/017910A1 discloses a kind of being suitable as and accumulates the Palmic acid handkerchief risperidone pharmaceutical composition of preparation by intramuscular or subcutaneous administrations.CN 101711752 A discloses biological double-layer osmotic pump controlled-release tablet of a kind of Palmic acid handkerchief risperidone and preparation method thereof.CN 102078309 A discloses a kind of novel Palmic acid handkerchief Risperidone dispersible tablet, has the advantages such as dispersion is rapid evenly, disintegration time is short, taking convenience.CN 102274164 A discloses the Injectable sustained release gel of handkerchief risperidone and derivant thereof, having prominent release little, the advantage that drug loading is high.But so far, not yet there are Patents or the bibliographical information of Palmic acid handkerchief risperidone intramuscular injection suspensoid.
Summary of the invention
The object of the present invention is to provide a kind of antipsychotic drug Palmic acid handkerchief risperidone intramuscular injection suspensoid and preparation method thereof.
The technical scheme of the present invention realizing above-mentioned purpose is as follows:
The invention provides a kind of Palmic acid handkerchief risperidone injection, described Palmic acid handkerchief risperidone intramuscular injection suspensoid consists of the following composition: the pH adjusting agent of the wetting agent of 1-70%, the stabilizing agent of 0-5%, 0.01-5%, the antioxidant of 0-2%, the isotonic agent of 0-20%.
Above-mentioned wetting agent be selected from polyoxyethylene castor oil, polysorbate 20, polysorbate 40, polyoxyethylene sorbitan monoleate, polyvidone, lecithin and Pluronic F-68 one or more, wherein preferably polyoxyethylene castor oil, polysorbate 20 and lecithin.
Aforementioned stable agent be selected from gelatin, methylcellulose, sodium carboxymethyl cellulose, pectin and PEG4000 one or more, wherein preferably gelatin, sodium carboxymethyl cellulose and PEG4000.
It is one or more pairs of that above-mentioned pH adjusting agent is selected from sodium citrate, citric acid, tartaric acid, sodium tartrate, sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium bicarbonate, sodium carbonate, wherein preferably citric acid sodium, citric acid, sodium dihydrogen phosphate, sodium hydrogen phosphate.
Above-mentioned antioxidant is selected from one or more of sodium sulfite, sodium sulfite, citric acid, sodium pyrosulfite and sodium thiosulfate, wherein preferably sodium sulfite and citric acid.
Above-mentioned isotonic agent be selected from sodium chloride, glucose, glycerol one or more, wherein preferably sodium chloride and glucose.
Above-described Palmic acid handkerchief risperidone injection, is characterised in that it is consist of the following composition: the stabilizing agent of 1-50% wetting agent, 0-2%, the pH adjusting agent of 0.01-4%, the antioxidant of 0-1%, the isotonic agent of 0-10%.
Above-described Palmic acid handkerchief risperidone intramuscular injection suspensoid is prepared from by following steps:
(1) wetting agent is added to the water, stirs, obtain mixture A;
(2) added in mixture A by antiseptic, stirring is mixed thoroughly, obtains mixture B;
(3) stabilizing agent is added in mixture B, stir simultaneously, obtain mixture C;
(4) isotonic agent, pH adjusting agent are joined in mixture C, stir, obtain mixture D;
(5) active constituents of medicine is dispersed in mixture D, stirs simultaneously, then homogenised mixture, control particle diameter < 15 μm.
Detailed description of the invention
Further illustrate the present invention by embodiment below, understand a kind of Palmic acid handkerchief risperidone intramuscular injection suspensoid further, but the present invention is not limited.
Injection prepared by following embodiment and comparative example, according to the preparation of 1L amount.Unless otherwise noted, all carry out with the homogenizer of same model.
embodiment 1 Palmic acid handkerchief risperidone injection (39m
g/0.25mL
) preparation
| Injection composition | Consumption g |
| Palmic acid handkerchief risperidone | 156 |
| Polysorbate 20 | 20 |
| Macrogol 4000 | 1 |
| Citric acid | 0.5 |
| Disodium hydrogen phosphate,anhydrous | 2 |
| Sodium dihydrogen phosphate-water | 2 |
| Water for injection | Add water to 1L |
Preparation technology:
(1) polysorbate 20 is added to the water, stirs, obtain mixture A;
(2) added in mixture A by citric acid, stirring is mixed thoroughly, obtains mixture B;
(3) Macrogol 4000 is added in mixture B, stir, obtain mixture C;
(4) sodium dihydrogen phosphate, sodium hydrogen phosphate are joined in mixture C, stir, obtain mixture D;
(5) Palmic acid handkerchief risperidone is dispersed in mixture D, stirs, then use homogenizer homogenised mixture, control particle diameter < 15 μm, often prop up loading amount 0.25mL.
embodiment 2 Palmic acid handkerchief risperidone injection (78mg/0.5mL
) preparation
| Injection composition | Consumption g |
| Palmic acid handkerchief risperidone | 156 |
| Polyoxyethylene castor oil | 10 |
| Sodium carboxymethyl cellulose | 1 |
| Sodium sulfite | 0.3 |
| Citric acid | 3 |
| Sodium citrate | 3 |
| Water for injection | Add water to 1L |
Preparation technology:
(1) polyoxyethylene castor oil is added to the water, stirs, obtain mixture A;
(2) added in mixture A by sodium sulfite, stirring is mixed thoroughly, obtains mixture B;
(3) sodium carboxymethyl cellulose is added in mixture B, stir, obtain mixture C;
(4) citric acid, sodium citrate are joined in mixture C, stir, obtain mixture D;
(5) Palmic acid handkerchief risperidone is dispersed in mixture D, stirs, then use homogenizer homogenised mixture, control particle diameter < 15 μm, often prop up loading amount 0.5mL.
embodiment 3 Palmic acid handkerchief risperidone injection (117mg/0.75mL
) preparation
| Injection composition | Consumption g |
| Palmic acid handkerchief risperidone | 156 |
| Polysorbate 20 | 40 |
| Gelatin | 1 |
| Citric acid | 0.5 |
| Disodium hydrogen phosphate,anhydrous | 1 |
| Sodium dihydrogen phosphate-water | 1 |
| Water for injection | Add water to 1L |
Preparation technology:
(1) polysorbate 20 is added to the water, stirs, obtain mixture A;
(2) citric acid is added in mixture A, stir, obtain mixture B;
(3) gelatin is added in mixture B, stir, obtain mixture C;
(4) sodium hydrogen phosphate, sodium dihydrogen phosphate are joined in mixture C, stir, obtain mixture D;
(5) Palmic acid handkerchief risperidone is dispersed in mixture D, stirs, then use homogenizer homogenised mixture, control particle diameter < 15 μm, often prop up loading amount 0.75mL.
embodiment 4 Palmic acid handkerchief risperidone injection (156mg/1mL
) preparation
| Injection composition | Consumption g |
| Palmic acid handkerchief risperidone | 156 |
| Lecithin | 15 |
| Sodium carboxymethyl cellulose | 2 |
| Sodium sulfite | 0.4 |
| Citric acid | 2 |
| Sodium citrate | 2 |
| Water for injection | Add water to 1L |
Preparation technology:
(1) lecithin is added to the water, stirs, obtain mixture A;
(2) sodium sulfite is added in mixture A, stir, obtain mixture B;
(3) sodium carboxymethyl cellulose is added in mixture B, stir, obtain mixture C;
(4) citric acid, sodium citrate join in mixture C, stir, obtain mixture D;
(5) Palmic acid handkerchief risperidone is dispersed in mixture D, stirs, then use homogenizer homogenised mixture, control particle diameter < 15 μm, often prop up loading amount 1.0mL.
embodiment 5 Palmic acid handkerchief risperidone injection (234mg/1.5mL
) preparation
| Injection composition | Consumption g |
| Palmic acid handkerchief risperidone | 234 |
| Polysorbate 20 | 35 |
| Sodium carboxymethyl cellulose | 2 |
| Sodium sulfite | 0.6 |
| Citric acid | 4 |
| Sodium citrate | 4 |
| Water for injection | Add water to 1L |
Preparation technology:
(1) polysorbate 20 is added to the water, stirs, obtain mixture A;
(2) added in mixture A by sodium sulfite, stirring is mixed thoroughly, obtains mixture B;
(3) sodium carboxymethyl cellulose is added in mixture B, stir, obtain mixture C;
(4) citric acid, sodium citrate are joined in mixture C, stir, obtain mixture D;
(5) Palmic acid handkerchief risperidone is dispersed in mixture D, stirs, then use homogenizer homogenised mixture, control particle diameter < 15 μm, often prop up loading amount 1.5mL.
test example 1: particle size distribution
the suspension type injection water for injection prepared by embodiment of the present invention 1-5 dissolves or dilution, and the suspensoid injectio granular size prepared to embodiment of the present invention 1-5 with sem observation is homogeneous, in irregular spherical or oval spherical.
test example 2: study on the stability
The sample prepared by above-described embodiment is placed 6 months under high temperature 40 DEG C, relative humidity 75% ± 5% condition, investigates the stability of sample.The results are shown in following table:
As seen from the above table, the Palmic acid handkerchief risperidone intramuscular injection suspensoid adopting prescription of the present invention and technique to prepare, particle size distribution meets the requirements, good stability.The present invention is durative action preparation, for the schizophrenic of 1 administration in January.
Claims (6)
1. a Palmic acid handkerchief risperidone injection, using handkerchief risperidone and derivant thereof as principal agent, described injection consists of the following composition: the pH adjusting agent of the wetting agent of 1-70%, the stabilizing agent of 0-5%, 0.01-5%, the antioxidant of 0-2%, the isotonic agent of 0-20%.
2. Palmic acid handkerchief risperidone injection according to claim 1, is characterized in that described wetting agent is one or more in polyoxyethylene castor oil, polysorbate 20, polysorbate 40, polyoxyethylene sorbitan monoleate, polyvidone, lecithin and Pluronic F-68; Stabilizing agent is one or more in gelatin, methylcellulose, sodium carboxymethyl cellulose, pectin and PEG4000; Antioxidant is one or more of sodium sulfite, sodium sulfite, citric acid, sodium pyrosulfite and sodium thiosulfate; Isotonic agent is one or more in sodium chloride, glucose, glycerol.
3. Palmic acid handkerchief risperidone injection according to claim 2, is characterized in that described wetting agent is selected from polyoxyethylene castor oil, polysorbate 20, polyoxyethylene sorbitan monoleate and lecithin; Stabilizing agent is selected from gelatin, sodium carboxymethyl cellulose and PEG4000; PH adjusting agent is to being selected from sodium citrate, citric acid, sodium dihydrogen phosphate, sodium hydrogen phosphate; Antioxidant is selected from sodium sulfite, sodium sulfite and citric acid; Isotonic agent is selected from sodium chloride and glucose.
4. Palmic acid handkerchief risperidone injection according to claim 1, it is characterized in that consisting of the following composition: the pH adjusting agent of the wetting agent of 1-50%, the stabilizing agent of 0-2%, 0.01-4%, the antioxidant of 0-1%, the isotonic agent of 0-10%.
5. Palmic acid handkerchief risperidone injection according to claim 1, is characterized in that, described Palmic acid handkerchief risperidone injection is prepared from by following steps:
(1) wetting agent is added to the water, stirs, obtain mixture A;
(2) added in mixture A by antiseptic, stirring is mixed thoroughly, obtains mixture B;
(3) stabilizing agent is added in mixture B, stir simultaneously, obtain mixture C;
(4) isotonic agent, pH adjusting agent are joined in mixture C, stir simultaneously, obtain mixture D;
(5) active constituents of medicine is dispersed in mixture D, stirs simultaneously, then homogenised mixture, control particle diameter < 15 μm.
6. Palmic acid handkerchief risperidone intramuscular injection suspensoid according to claim 1 can be used for be grown up schizoid emergency aid and treatment and maintaining treatment, belongs to field of pharmaceutical preparations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510001427.8A CN104586764A (en) | 2015-01-05 | 2015-01-05 | Intramuscular injection slow release suspension agent containing paliperidone palmitate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510001427.8A CN104586764A (en) | 2015-01-05 | 2015-01-05 | Intramuscular injection slow release suspension agent containing paliperidone palmitate and preparation method thereof |
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|---|---|
| CN104586764A true CN104586764A (en) | 2015-05-06 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510001427.8A Pending CN104586764A (en) | 2015-01-05 | 2015-01-05 | Intramuscular injection slow release suspension agent containing paliperidone palmitate and preparation method thereof |
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| Country | Link |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106137985A (en) * | 2016-08-04 | 2016-11-23 | 齐鲁制药有限公司 | A kind of stable Palmic acid 9-hydroxy-risperidone durative action preparation |
| CN108969478A (en) * | 2018-08-29 | 2018-12-11 | 江南大学 | A kind of Memantine difficulty soluble salt is slow-release injected and preparation method thereof |
| CN110279659A (en) * | 2019-07-08 | 2019-09-27 | 华裕(无锡)制药有限公司 | Palmitinic acid 9-hydroxy-risperidone preparation and preparation method thereof |
-
2015
- 2015-01-05 CN CN201510001427.8A patent/CN104586764A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106137985A (en) * | 2016-08-04 | 2016-11-23 | 齐鲁制药有限公司 | A kind of stable Palmic acid 9-hydroxy-risperidone durative action preparation |
| CN106137985B (en) * | 2016-08-04 | 2019-03-08 | 齐鲁制药有限公司 | A kind of stable palmitinic acid 9-hydroxy-risperidone durative action preparation |
| CN108969478A (en) * | 2018-08-29 | 2018-12-11 | 江南大学 | A kind of Memantine difficulty soluble salt is slow-release injected and preparation method thereof |
| CN110279659A (en) * | 2019-07-08 | 2019-09-27 | 华裕(无锡)制药有限公司 | Palmitinic acid 9-hydroxy-risperidone preparation and preparation method thereof |
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| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150506 |
|
| WD01 | Invention patent application deemed withdrawn after publication |