CN103690497B - Desmopressin acetate sublingual tablet and preparation method thereof - Google Patents
Desmopressin acetate sublingual tablet and preparation method thereof Download PDFInfo
- Publication number
- CN103690497B CN103690497B CN201310673460.6A CN201310673460A CN103690497B CN 103690497 B CN103690497 B CN 103690497B CN 201310673460 A CN201310673460 A CN 201310673460A CN 103690497 B CN103690497 B CN 103690497B
- Authority
- CN
- China
- Prior art keywords
- desmopressin acetate
- sublingual tablet
- preparation
- desmopressin
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a desmopressin acetate sublingual tablet and a preparation method thereof. Each desmopressin acetate sublingual tablet comprises a filling, a pH modifier, a disintegrating agent, a lubricant and an adhesive. The preparation method comprises the following steps: diluting desmopressin acetate by using the pH modifier; uniformly mixing the filling agent and the 60 percent disintegrating agent, preparing into paste by adding water in the adhesive; mixing the pasty adhesive with the uniformly mixed filling agent and disintegrating agent to prepare a soft material, pelleting and drying the soft material, and granulating into blank particles after drying; finally, uniformly mixing the diluted desmopressin acetate with the left disintegrating agent, the lubricant and the blank particles, and tabletting to obtain the desmopressin acetate sublingual tablet. The desmopressin acetate sublingual tablet provided by the invention is sublingually administrated, is high in effect taking speed and absorption efficiency, beneficial to administration by a child, capable of greatly lowering the production cost, and beneficial to industrial mass production.
Description
Technical field
The invention belongs to field of pharmaceutical chemistry technology, be specifically related to a kind of desmopressin acetate sublingual tablet and preparation method thereof.
Background technology
The analog that desmopressin acetate (English Desmopressin Acetate by name) is natural smart ammonia salt vassopressin, system carries out the change of two places to the chemical constitution of natural hormone and obtain, i.e. 1-cysteine deaminate and with 8-D-arginine replacement 8-L-arginine.Desmopressin acetate is mainly used in treatment central diabetes insipidus, enuresis nocturna and hemophilia etc., also for the test of kidney urine concentrating function, also can be used as postoperation hemostatic.
Desmopressin acetate clinical invasive can be made to treat or diagnostic operation time long bleeding time shorten or normalization; or make because of uremia, liver cirrhosis, congenital or drug induccd platelet function is bad, and the blood phenomenon of the bleeding time of unknown etiology long patient is controlled.Desmopressin acetate can be used for hemorrhage control or prevention when slight hemophilia A patients that test dose is positive and angiohemophilia patient carry out small-sized operation.To special case, even can be used for treatment and prevention moderate state of an illness patient.Diabetes insipidus: adult 20 ~ 40ug/d; Child 10 ~ 20ug/d, divides and takes for 1 ~ 3 time.Enuresis: 10 ~ 40ug/d, uses before sleeping.Kidney concentrating function is tested: adult 40ug, more than 1 years old child 10 ~ 20ug.Therapeutic Bleeding control or operation consent prevent hemorrhage: quiet note 0.3ug/kg.
At present, the synthesis of the desmopressin acetate of bibliographical information mainly contains two kinds.The first is liquid phase synthesis, aminoacid aminoacid ground coupling in the basic conditions, every coupling aminoacid all needs to carry out single step purification, finally sample solution pH value is adjusted to 6.5-7.0, and the oxidation of oxidizer potassium cyanide forms disulfide bond and obtains the thick peptide of Desmopressin.The method of liquid phase synthesis is consuming time, and operation quite bothers, and yield is very low, is unfavorable for that industrialization is produced.Second method is the method by solid phase synthesis, with the Sieber Amide resin of Fmoc-Gly-OH and suitable substitution degree, the mode of aminoacid coupling is one by one adopted to obtain linear Desmopressin resin, oxidant is made with iodine, phase oxidative disulfide bond ring formation obtains the resin of Desmopressin, and Desmopressin cuts down from resin by the method finally by cracking, obtains the thick peptide of Desmopressin, then through HPLC purification, anion exchange method is adopted to obtain desmopressin acetate.But the substitution degree of this solid phase synthesis resin can not be too high, and the bad control of oxidizing process, although it is fairly simple that operation seems, oxidization-hydrogenation ratio is low, and side reaction is many.Purification ratio is more difficult, and product quality is not high.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of desmopressin acetate sublingual tablet and preparation method thereof.Adopt the desmopressin acetate sublingual tablet that technical solution of the present invention is obtained, adopt sublingual administration, rapid-action, absorption efficiency is high, is beneficial to child simultaneously and takes medicine, and greatly can reduce production cost, be beneficial to industrialized great production.
In order to solve the problem, the technical solution used in the present invention is:
The invention provides a kind of desmopressin acetate sublingual tablet, with the specification of every sheet 50mg for benchmark, every sheet desmopressin acetate sublingual tablet is by desmopressin acetate 0.1 ~ 0.2mg, filler 30 ~ 40mg, pH adjusting agent 5 ~ 20mg, disintegrating agent 1 ~ 2.5mg, lubricant 1 ~ 2.5mg and binding agent 0.5 ~ 5mg form.
According to above-mentioned desmopressin acetate sublingual tablet, described filler is lactose, glucose, maltose, fructose or mannitol; Described pH adjusting agent is malic acid or fumaric acid; Described disintegrating agent is polyvinylpolypyrrolidone; Described lubricant is Macrogol 4000, polyethylene glycol 6000 or PEG 8000; Described binding agent is starch or dextrin.
A preparation method for desmopressin acetate sublingual tablet, described preparation method comprises the following steps:
(1) first according to the various raw material of proportioning raw materials proportions of above-mentioned every sheet desmopressin acetate sublingual tablet, the desmopressin acetate pH adjusting agent of preparation is passed and doubly dilutes 25 ~ 200 times, obtain the desmopressin acetate after diluting;
(2) blank granules is prepared:
1. the filler of preparation and 60% disintegrating agent are crossed 100 mesh sieves, mix homogeneously, for subsequent use;
2. the binding agent of preparation is added water and make paste adhesive;
3. the material that 1. paste adhesive step 2. made and step mix homogeneously carries out mix homogeneously, makes soft material;
4. soft material step 3. made 20 mesh sieves are granulated, sabot;
5. it is dry that wet grain step 4. made is placed in 50 ~ 60 DEG C of baking ovens, turns over every 20min, and controlling moisture after dry is 3 ~ 5%;
6. by step 5. dried granule cross 18 mesh sieves and carry out granulate, make blank granules;
(3) desmopressin acetate after step (1) being diluted and remaining 40% disintegrating agent, lubricant and the blank granules mix homogeneously made, conventionally carry out tabletting, obtain desmopressin acetate sublingual tablet;
(4) sampling detects, qualified rear packaging.
According to the preparation method of above-mentioned desmopressin acetate sublingual tablet, described in step (2), the binding agent of preparation is added water and make paste adhesive, the addition of its water is 8 ~ 10 times of binding agent quality.
positive beneficial effect of the present invention:
1, the desmopressin acetate sublingual tablet adopting technical solution of the present invention obtained, adopt sublingual administration, rapid-action, absorption efficiency is high, is beneficial to child simultaneously and takes medicine, and greatly can reduce production cost, be beneficial to industrialized great production.
2, the desmopressin acetate sublingual tablet that technical solution of the present invention is obtained is utilized, sublingual mucosal absorption is adopted to carry out the administration of desmopressin acetate when taking, make desmopressin acetate enter blood circulation fast through sublingual mucosa, onset is faster than oral.Adopt sublingual administration, than oral tablet, absorption efficiency is higher, tablet format is reduced, greatly reduces costs.Further, adopt sublingual administration, be more conducive to child than drug administration by injection and accept.
3, in desmopressin acetate sublingual tablet pharmaceutical formulation of the present invention, filler adopts lactose, glucose, maltose or fructose etc., make medicine mouthfeel good, pH adjusting agent guarantees the sour environment after medicine disintegrate, improves medicine through sublingual mucosa absorption efficiency, improves mouthfeel simultaneously.In formula, disintegrating agent adopts inside and outside mode of adding in preparation process, thus guarantees that medicine is at Sublingual fater disintegration.
4, the whole production process of desmopressin acetate sublingual tablet of the present invention is simple, is beneficial to industrialized great production.
accompanying drawing illustrates:
The dissolution in vitro of Fig. 1 embodiment of the present invention 1 gained three batches of different samples under pH6.8 condition.
Indicate: sublingual lozenge is mainly at sublingual disintegration, and residing environment is mainly saliva.Human saliva normal ph is 6.6 ~ 7.1.Therefore, the present invention take pH6.8 as the In Vitro Dissolution test that solvent carries out desmopressin acetate sublingual tablet.
detailed description of the invention:
Embodiment 1:
Desmopressin acetate sublingual tablet of the present invention, with the specification of every sheet 50mg for benchmark, the raw material of every sheet desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.1mg, lactose 37.4mg, malic acid 8.5mg, polyvinylpolypyrrolidone 1.5mg, Macrogol 4000 1.5mg and starch 1mg.
The present embodiment is the raw material composition of benchmark according to above-mentioned every sheet 50mg specification, the raw material producing 2000 desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.2g, lactose 74.8g, malic acid 17g, polyvinylpolypyrrolidone 3g, Macrogol 4000 3g and starch 2g.
The dissolution in vitro of the embodiment of the present invention 1 gained three batches of different samples under pH6.8 condition, refers to accompanying drawing 1.
Embodiment 2:
Desmopressin acetate sublingual tablet of the present invention, with the specification of every sheet 50mg for benchmark, the raw material of every sheet desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.1mg, glucose 34.9mg, malic acid 9mg, polyvinylpolypyrrolidone 2mg, polyethylene glycol 6000 1.5mg and starch 2.5mg.
The present embodiment is the raw material composition of benchmark according to above-mentioned every sheet 50mg specification, the raw material producing 2000 desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.2g, glucose 69.8g, malic acid 18g, polyvinylpolypyrrolidone 4g, polyethylene glycol 6000 3g and starch 5g.
Embodiment 3:
Desmopressin acetate sublingual tablet of the present invention, with the specification of every sheet 50mg for benchmark, the raw material of every sheet desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.1mg, maltose 34.4mg, fumaric acid 9mg, polyvinylpolypyrrolidone 2.5mg, PEG 8000 1.5mg and dextrin 2.5mg.
The present embodiment is the raw material composition of benchmark according to above-mentioned every sheet 50mg specification, the raw material producing 2000 desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.2g, maltose 68.8g, fumaric acid 18g, polyvinylpolypyrrolidone 5g, PEG 8000 3g and dextrin 5g.
Embodiment 4:
Desmopressin acetate sublingual tablet of the present invention, with the specification of every sheet 50mg for benchmark, the raw material of every sheet desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.2mg, lactose 35.3mg, malic acid 8.5mg, polyvinylpolypyrrolidone 2mg, polyethylene glycol 6000 1.5mg and starch 2.5mg.
The present embodiment is the raw material composition of benchmark according to above-mentioned every sheet 50mg specification, the raw material producing 2000 desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.4g, lactose 70.6g, malic acid 17g, polyvinylpolypyrrolidone 4g, polyethylene glycol 6000 3g and starch 5g.
Embodiment 5:
Desmopressin acetate sublingual tablet of the present invention, with the specification of every sheet 50mg for benchmark, the raw material of every sheet desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.2mg, mannitol 35.8mg, fumaric acid 8.5mg, polyvinylpolypyrrolidone 2.5mg, PEG 8000 1.5mg and starch 1.5mg.
The present embodiment is the raw material composition of benchmark according to above-mentioned every sheet 50mg specification, the raw material producing 2000 desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.4g, mannitol 71.6g, fumaric acid 17g, polyvinylpolypyrrolidone 5g, PEG 8000 3g and starch 3g.
Embodiment 6:
Desmopressin acetate sublingual tablet of the present invention, with the specification of every sheet 50mg for benchmark, the raw material of every sheet desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.2mg, fructose 34.3mg, malic acid 8.5mg, polyvinylpolypyrrolidone 2.5mg, Macrogol 4000 2mg and dextrin 2.5mg.
The present embodiment is the raw material composition of benchmark according to above-mentioned every sheet 50mg specification, the raw material producing 2000 desmopressin acetate sublingual tablet consists of: desmopressin acetate 0.4g, fructose 68.6g, malic acid 17g, polyvinylpolypyrrolidone 5g, Macrogol 4000 4g and dextrin 5g.
Embodiment 7:
The preparation method of above-described embodiment 1 ~ 6 desmopressin acetate sublingual tablet:
(1) first according to the various raw material of proportioning raw materials proportions of the every sheet desmopressin acetate sublingual tablet in embodiment 1-6 described in any embodiment, the desmopressin acetate pH adjusting agent of preparation is passed and doubly dilutes 25 ~ 200 times, obtain the desmopressin acetate after diluting;
(2) blank granules is prepared:
1. the filler of preparation and 60% disintegrating agent are crossed 100 mesh sieves, mix homogeneously, for subsequent use;
2. the binding agent of preparation is added water and make paste adhesive; The addition of its water is 8 ~ 10 times of binding agent quality;
3. the material that 1. paste adhesive step 2. made and step mix homogeneously carries out mix homogeneously, makes soft material;
4. soft material step 3. made 20 mesh sieves are granulated, sabot;
5. it is dry that wet grain step 4. made is placed in 50 ~ 60 DEG C of baking ovens, turns over every 20min, and controlling moisture after dry is 3 ~ 5%;
6. by step 5. dried granule cross 18 mesh sieves and carry out granulate, make blank granules;
(3) desmopressin acetate after step (1) being diluted and remaining 40% disintegrating agent, lubricant and the blank granules mix homogeneously made, conventionally carry out tabletting, obtain desmopressin acetate sublingual tablet;
(4) sampling detects, qualified rear packaging.
Embodiment 8: product desmopressin acetate sublingual tablet disintegration time of the present invention measures and result
Get 1,10ml test tube (diameter 1.5cm), add distilled water 2ml, test tube inclination 45° angle, carefully product desmopressin acetate sublingual tablet of the present invention is dropped in vitro, the record tablet disintegrates time.Measurement result refers to table 1.
Claims (2)
1. a desmopressin acetate sublingual tablet, it is characterized in that, with the specification of every sheet 50mg for benchmark, every sheet desmopressin acetate sublingual tablet is by desmopressin acetate 0.1 ~ 0.2mg, filler 30 ~ 40mg, pH adjusting agent 5 ~ 20mg, disintegrating agent 1 ~ 2.5mg, lubricant 1 ~ 2.5mg and binding agent 0.5 ~ 5mg form;
Described filler is lactose, glucose, maltose, fructose or mannitol; Described pH adjusting agent is malic acid or fumaric acid; Described disintegrating agent is polyvinylpolypyrrolidone; Described lubricant is Macrogol 4000, polyethylene glycol 6000 or PEG 8000; Described binding agent is starch or dextrin;
Described desmopressin acetate sublingual tablet is prepared from by the following method:
(1) first according to the various raw material of proportioning raw materials proportions of above-mentioned every sheet desmopressin acetate sublingual tablet, the desmopressin acetate pH adjusting agent of preparation is passed and doubly dilutes 25 ~ 200 times, obtain the desmopressin acetate after diluting;
(2) blank granules is prepared:
1. the filler of preparation and 60% disintegrating agent are crossed 100 mesh sieves, mix homogeneously, for subsequent use;
2. the binding agent of preparation is added water and make paste adhesive;
3. the material that 1. paste adhesive step 2. made and step mix homogeneously carries out mix homogeneously, makes soft material;
4. soft material step 3. made 20 mesh sieves are granulated, sabot;
5. it is dry that wet grain step 4. made is placed in 50 ~ 60 DEG C of baking ovens, turns over every 20min, and controlling moisture after dry is 3 ~ 5%;
6. by step 5. dried granule cross 18 mesh sieves and carry out granulate, make blank granules;
(3) desmopressin acetate after step (1) being diluted and remaining 40% disintegrating agent, lubricant and the blank granules mix homogeneously made, conventionally carry out tabletting, obtain desmopressin acetate sublingual tablet;
(4) sampling detects, qualified rear packaging.
2. desmopressin acetate sublingual tablet according to claim 1, is characterized in that: the addition of water is 8 ~ 10 times of binding agent quality.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310673460.6A CN103690497B (en) | 2013-12-12 | 2013-12-12 | Desmopressin acetate sublingual tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310673460.6A CN103690497B (en) | 2013-12-12 | 2013-12-12 | Desmopressin acetate sublingual tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103690497A CN103690497A (en) | 2014-04-02 |
| CN103690497B true CN103690497B (en) | 2015-04-22 |
Family
ID=50352271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310673460.6A Active CN103690497B (en) | 2013-12-12 | 2013-12-12 | Desmopressin acetate sublingual tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103690497B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114432424B (en) * | 2021-12-27 | 2023-06-27 | 南通联亚药业股份有限公司 | Stable aluminum-plastic package desmopressin tablet |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1826099B (en) * | 2003-07-25 | 2010-06-09 | 凡林有限公司 | Pharmaceutical composition as solid dosage form and method for manufacturing thereof |
| CN102423485B (en) * | 2011-12-08 | 2014-08-06 | 赵联华 | Oral composition containing desmopressin acetate and preparation method for oral composition |
-
2013
- 2013-12-12 CN CN201310673460.6A patent/CN103690497B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN103690497A (en) | 2014-04-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1300590A (en) | Use of coating as taste masking agent for oral preparation | |
| CN101278932A (en) | Sustained release medicinal compositions containing Zaltoprofen, preparation method and application thereof | |
| CN104546806A (en) | Oral cavity instant film containing risperidone and preparation method for oral cavity instant film | |
| CN103690497B (en) | Desmopressin acetate sublingual tablet and preparation method thereof | |
| TWI343818B (en) | ||
| CN103356488A (en) | Capecitabine granule and preparation method thereof | |
| CN103721267A (en) | Composition containing desloratadine citrate disodium | |
| CN114886860A (en) | Acetylcysteine pharmaceutical composition, preparation and preparation process thereof | |
| CN101502492B (en) | Method for preparing clarithromycin granule without bitter taste | |
| CN104622825A (en) | Azithromycin dispersible tablet | |
| CN104257624A (en) | Novel effervescent and disintegrative premix and preparation method thereof | |
| CN101120928B (en) | Vitamin K1 orally disintegrating tablets preparation and preparation method thereof | |
| CN1679567A (en) | Granules of clarityne and their production | |
| RU2260440C1 (en) | Method for preparing preparation "alloocholum" | |
| CN110755404B (en) | Azithromycin pharmaceutical composition and preparation method thereof | |
| CN103405394A (en) | Metoprolol tartrate sustained release tablet and preparation method thereof | |
| CN106265725A (en) | A kind of calcium carbonate taste masked particle agent and preparation method thereof | |
| CN102488689B (en) | Compound zinc gluconateand ibuprofen granule capable of curing cold and preparation method thereof | |
| CN101002790B (en) | Slow releace tablets of clarithromycin, and its preparing method | |
| CN101249080A (en) | Acetylkitasamycin dispersible tablet and method of preparing the same | |
| CN104958264A (en) | Oxymatrine solid dispersion-supported floating sustained-release pellet for stomach and preparation method of oxymatrine solid dispersion-supported floating sustained-release pellet | |
| CN117122701B (en) | Potassium chloride granule preparation and preparation method thereof | |
| CN109276551A (en) | A kind of Ornidazole oral disintegrating tablet and preparation method thereof | |
| CN108272745A (en) | A kind of melbine/ursolic acid nano oral preparation and preparation method thereof | |
| CN1634077A (en) | Orally disintegrating tablet of levonogestrel and its preparing process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |