CN108606957A - A kind of oral slow-releasing preparation of the peptide containing Suo Malu and preparation method thereof - Google Patents
A kind of oral slow-releasing preparation of the peptide containing Suo Malu and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to drug composition oral sustained release preparations of a kind of peptide containing Suo Malu and preparation method thereof, it is characterized in that the active constituents of medicine is 1 analog Suo Malu peptides of GLP, it additionally includes and Suo Malu peptides sulfonylureas with synergy, biguanides or thiazolidinediones hypoglycemic medicine, it will be in this active constituents of medicine package to slow releasing carrier material, it is prepared into sustained-release micro-spheres, then it is mixed with pharmaceutically acceptable auxiliary material and is pressed into the effigurate tablet of tool, for being administered orally, to play the role of long-acting slow-release.Oral slow-releasing preparation prepared by the present invention not only changes the conventional administration route of polypeptide drug, but also extends the action time of polypeptide drug, hence it is evident that improves the compliance of diabetic's medication, improves therapeutic effect.
Description
Technical field
The present invention relates to technical field of medicine more particularly to the oral slow-releasing preparations and its system of a kind of peptide containing Suo Malu
Preparation Method.
Background technology
With the development and improvement of living standard of global economy, living-pattern preservation and aging of population, glycosuria
Sick illness rate is worldwide in rising trend, and it is public strong to become the another serious harm after cardiovascular and cerebrovascular disease, tumour
The Chronic Non-Communicable Diseases of health.Diabetes main Types include Type I diabetes, type II diabetes, gestational diabetes and
Other specific type diabetes.Wherein, the ratio shared by type II diabetes is about 95%.Currently, mainly there is four class drugs available
In the blood glucose level for reducing patients with NIDDM：Sulphonylurea, such as gliquidone, Glimepiride, gliclazide；It is double
Guanidine antidiabetic drug, such as melbine；Thiazolidinediones antidiabetic drug, such as Ciglitazone, Pioglitazone, Rosiglitazone；GLP-1 classes
Like object antidiabetic drug, such as Liraglutide, albiglutide, Du Lalu peptides, Suo Malu peptides.
Suo Malu peptides are a kind of novel long-acting glucagon peptide -1 (GLP-1) analogs, with concentration of glucose according to
Rely property mechanism insulin secretion accelerating and glucagon suppression secretion, patients with NIDDM blood glucose level can be made to greatly improve,
And risk of hypoglycemia is relatively low.Currently, Novo Nordisk is shown in II clinical trial phase of Suo Malu peptides oral preparation ground, reduce
The ability of patients with NIDDM glycosylated hemoglobin is suitable with Suo Malu peptide ejection preparations.But Suo Malu peptide peroral dosage forms
The active constituent dosage needed is 300 times of subcutaneous injection agent, i.e., to take orally Suo Malu peptide 40mg daily, patient can be caused to spend
It is excessively high.Therefore Suo Malu peptides and other kinds of hypoglycemic drug are combined, other than it can ensure hypoglycemic effect, may be used also
To reduce the dosage of Suo Malu peptides, to reduce drug production cost.
Invention content
The problem to be solved in the present invention is to provide a kind of oral slow-releasing preparation of the peptide containing Suo Malu and preparation method thereof, to subtract
The active constituent dosage of few Suo Malu peptides reduces the production cost of Suo Malu peptides, while control cord horse Shandong peptide and other antidiabetic drugs
The slow release of object stablizes curative effect and improves the compliance of patient.
In order to solve the above technical problems, the present invention adopts the following technical scheme that：
A kind of oral slow-releasing preparation of the peptide containing Suo Malu, mainly by the sustained-release micro-spheres of the active constituent of peptide medicine containing Suo Malu and
Other pharmaceutically acceptable auxiliary materials are directly compressed into the effigurate tablet of tool and form, wherein sustained-release micro-spheres are by containing rope horse
Active constituents of medicine, slow releasing carrier material and other the pharmaceutically acceptable auxiliary materials composition of Shandong peptide.
By mass percentage, the active constituents of medicine of the peptide containing Suo Malu is 1.2%~10%, slow-released carrier material
Material is 60%~90%, other pharmaceutically acceptable auxiliary materials are 5%~30%.
Further, the sustained-release micro-spheres of the active constituent of peptide medicine containing Suo Malu prepared by W1/O/W2 multi-emulsion methods and
At.
Wherein, the average grain diameter of the sustained-release micro-spheres of the active constituent of peptide medicine containing Suo Malu is 0.5 micron~450 micro-
Rice, preferably 20 microns~240 microns.
Suo Malu peptide medicines active constituent of the present invention is Suo Malu peptides and has synergistic effect with Suo Malu peptides
Sulfonylureas, biguanides or thiazolidinediones hypoglycemic medicine.
Preferably, the mass ratio of the Suo Malu peptides and hypoglycemic medicine with synergy is 1:1~5:1.
Preferably, the sulfonylureas drugs for diabetes can be selected from gliclazide, Glimepiride, gliquidone；Biguanides
It can be selected from melbine；Thiazolidinediones antidiabetic drug can be selected from Ciglitazone, Pioglitazone, Rosiglitazone.
The slow releasing carrier material can be selected from cellulose acetate, ethyl cellulose, polyethylene, polymethyl methacrylate
In it is one or more.
Other acceptable auxiliary materials are drug release regulator in the sustained-release micro-spheres Chinese pharmacology comprising polyethylene glycol is spat
It is one or more in temperature -80, mannitol.
In sustained-release oral preparation, further include N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate, filler, adhesive and
Lubricant.
In the present invention, N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is used as delivery agents.
Preferably, filler can be selected from one or more in lactose, pregelatinized starch, microcrystalline cellulose；Adhesive can
It is one or more in sodium carboxymethylcellulose, hydroxypropyl cellulose；Lubricant can be selected from superfine silica gel powder, magnesium stearate,
It is one or more in talcum powder.
In addition, the present invention also provides a kind of preparation method of oral slow-releasing preparation, technique is as follows：
1. weighing the active constituents of medicine of the peptide containing Suo Malu, slow releasing carrier material and drug release respectively according to recipe quantity to adjust
Agent；The active constituents of medicine of drug release regulator and the peptide containing Suo Malu is dissolved in the water, as inner aqueous phase W1；Slow-released carrier is dissolved in
In organic solvent, as organic phase O；Polyvinyl alcohol is soluble in water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, ultrasonic emulsification forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, ultrasonic emulsification forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, 3 times are washed with water, 40~60
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after DEG C dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with filler and/or adhesive, dry granulation
Obtain a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with lubricant and/or filler, dry granulation obtains
To b；
7. 5., 6. particle and lubricant that step is obtained mix, direct tablet compressing is to get peptide containing Suo Malu
Oral slow-releasing preparation.
Heretofore described ultrasonic emulsification equipment is ultrasonic emulsification instrument, and ultrasonic power is 120W~600W, preferably 200W
~450W, ultrasonic time are 4min~25min, preferably 5min~12min.
Preferably, the organic solvent is selected from dichloromethane, ethyl acetate or acetone.
It is highly preferred that the organic solvent is selected from dichloromethane.
Description of the drawings
Fig. 1 is the oral slow-releasing preparation tablets in vitro result figure of embodiment 1,3,7,10.
Specific implementation mode：
It is further illustrated the present invention below by embodiment.It should be understood as：The embodiment of the present invention is only used for
Illustrate the present invention and provide, rather than limiting the invention, to the simple of the present invention under the premise of technical solution of the present invention
Improvement all belongs to the scope of protection of the present invention.
Embodiment 1
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides, melbine, cellulose acetate, ethyl cellulose, polyethylene glycol respectively according to recipe quantity；
Polyethylene glycol, Suo Malu peptides, melbine are dissolved in 1mL water, as inner aqueous phase W1；Cellulose acetate is dissolved in 10mL bis-
In chloromethanes, as organic phase O；Polyvinyl alcohol is dissolved in 50mL water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, power 250W ultrasonic emulsifications 10min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 250W ultrasonic emulsifications 10min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, 3 times are washed with water, 40~60
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after DEG C dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with lactose and sodium carboxymethylcellulose, dry method system
Grain obtains a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with superfine silica gel powder, dry granulation obtains b；
7. 5., 6. particle and superfine silica gel powder that step is obtained mix, direct tablet compressing is to get containing Suo Malu
The oral slow-releasing preparation of peptide.
Embodiment 2
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides, Ciglitazone, cellulose acetate, polyethylene, Tween-80 respectively according to recipe quantity；It will spit
Temperature -80, Suo Malu peptides, Ciglitazone are dissolved in 2mL water, as inner aqueous phase W1；Cellulose acetate, polyethylene are dissolved in 10mL bis-
In chloromethanes, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, power 300W ultrasonic emulsifications 8min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 300W ultrasonic emulsifications 8min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, 3 times are washed with water, 40~60
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after DEG C dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with lactose and sodium carboxymethylcellulose, dry method system
Grain obtains a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with superfine silica gel powder, dry granulation obtains b；
7. 5., 6. particle and superfine silica gel powder that step is obtained mix, direct tablet compressing is to get containing Suo Malu
The oral slow-releasing preparation of peptide.
Embodiment 3
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides, Pioglitazone, ethyl cellulose, polyethylene, mannitol respectively according to recipe quantity；By sweet dew
Alcohol, Suo Malu peptides, Pioglitazone are dissolved in 2mL water, as inner aqueous phase W1；Ethyl cellulose, polyethylene are dissolved in 10mL dichloros
In methane, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, power 350W ultrasonic emulsifications 7min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 350W ultrasonic emulsifications 7min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 60 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with microcrystalline cellulose and hydroxypropyl cellulose, it is dry
Method pelletizes to obtain a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with microcrystalline cellulose, talcum powder, dry granulation obtains
To b；
7. 5., 6. particle and talcum powder that step is obtained mix, direct tablet compressing is to get peptide containing Suo Malu
Oral slow-releasing preparation.
Embodiment 4
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides respectively according to recipe quantity, Rosiglitazone, polymethacrylate resin, ethyl cellulose, spitting
Temperature -80；Tween-80, Suo Malu peptides, Rosiglitazone are dissolved in 2mL water, as inner aqueous phase W1；Polymethacrylate resin,
Ethyl cellulose is dissolved in 10mL dichloromethane, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase
W2；
2. inner aqueous phase W1 is added in organic phase O, power 450W ultrasonic emulsifications 8min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 450W ultrasonic emulsifications 8min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 55 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with sodium carboxymethylcellulose, dry granulation obtains
a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with microcrystalline cellulose, dry granulation obtains b；
7. 5., 6. particle and magnesium stearate that step is obtained mix, direct tablet compressing is to get containing Suo Malu
The oral slow-releasing preparation of peptide.
Embodiment 5
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides, gliclazide, polyethylene, ethyl cellulose, polyethylene glycol respectively according to recipe quantity；It will gather
Ethylene glycol, Suo Malu peptides, gliclazide are dissolved in 3mL water, as inner aqueous phase W1；Polyethylene, ethyl cellulose are dissolved in 15mL
In dichloromethane, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, power 500W ultrasonic emulsifications 5min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 500W ultrasonic emulsifications 5min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 55 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with lactose, sodium carboxymethylcellulose, dry method system
Grain obtains a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with lactose, superfine silica gel powder, dry granulation obtains b；
7. 5., 6. particle and superfine silica gel powder that step is obtained mix, direct tablet compressing is to get containing Suo Malu
The oral slow-releasing preparation of peptide.
Embodiment 6
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides respectively according to recipe quantity, Glimepiride, cellulose acetate, polymethacrylate resin, gathering
Ethylene glycol；Polyethylene glycol, Suo Malu peptides, Glimepiride are dissolved in 3mL water, as inner aqueous phase W1；Cellulose acetate, poly- first
Base acrylic resin is dissolved in 15mL dichloromethane, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase
W2；
2. inner aqueous phase W1 is added in organic phase O, power 300W ultrasonic emulsifications 10min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 300W ultrasonic emulsifications 10min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 45 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with hydroxypropyl methylcellulose, dry granulation obtains a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with talcum powder, dry granulation obtains b；
7. 5., 6. particle and talcum powder that step is obtained mix, direct tablet compressing is to get peptide containing Suo Malu
Oral slow-releasing preparation.
Embodiment 7
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides, gliquidone, ethyl cellulose, polyethylene, mannitol respectively according to recipe quantity；By sweet dew
Alcohol, Suo Malu peptides, gliquidone are dissolved in 3mL water, as inner aqueous phase W1；Ethyl cellulose, polyethylene are dissolved in 15mL dichloros
In methane, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, power 300W ultrasonic emulsifications 10min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 300W ultrasonic emulsifications 10min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 50 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with sodium carboxymethylcellulose, dry granulation obtains
a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with magnesium stearate, dry granulation obtains b；
7. 5., 6. particle and magnesium stearate that step is obtained mix, direct tablet compressing is to get containing Suo Malu
The oral slow-releasing preparation of peptide.
Embodiment 8
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides, pioglitazone, ethyl cellulose, cellulose acetate, polyethylene glycol respectively according to recipe quantity；
Polyethylene glycol, Suo Malu peptides, pioglitazone are dissolved in 5mL water, as inner aqueous phase W1；Ethyl cellulose, cellulose acetate
It is dissolved in 20mL dichloromethane, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, power 280W ultrasonic emulsifications 9min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 280W ultrasonic emulsifications 9min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 50 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with sodium carboxymethylcellulose, dry granulation obtains
a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with magnesium stearate, dry granulation obtains b；
7. 5., 6. particle and magnesium stearate that step is obtained mix, direct tablet compressing is to get containing Suo Malu
The oral slow-releasing preparation of peptide.
Embodiment 9
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides, Ciglitazone, ethyl cellulose, polyethylene, Tween-80 respectively according to recipe quantity；It will spit
Temperature -80, Suo Malu peptides, Ciglitazone are dissolved in 5mL water, as inner aqueous phase W1；Ethyl cellulose, polyethylene are dissolved in 20mL bis-
In chloromethanes, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, power 280W ultrasonic emulsifications 9min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 280W ultrasonic emulsifications 9min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 50 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with sodium carboxymethylcellulose, dry granulation obtains
a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with microcrystalline cellulose, dry granulation obtains b；
7. 5., 6. particle and superfine silica gel powder that step is obtained mix, direct tablet compressing is to get containing Suo Malu
The oral slow-releasing preparation of peptide.
Embodiment 10
The oral slow-releasing preparation prescription (every content) of the peptide containing Suo Malu
Former, auxiliary material is crossed to 80 mesh sieve respectively, it is spare, configure 1000 sample recipe quantities.
1. weighing Suo Malu peptides, melbine, cellulose acetate, polyethylene, Tween-80 respectively according to recipe quantity；It will spit
Temperature -80, Suo Malu peptides, melbine are dissolved in 5mL water, as inner aqueous phase W1；Cellulose acetate, polyethylene are dissolved in 20mL bis-
In chloromethanes, as organic phase O；Polyvinyl alcohol is dissolved in 100mL water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, power 280W ultrasonic emulsifications 9min forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, power 280W ultrasonic emulsifications 9min forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 50 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with sodium carboxymethylcellulose, dry granulation obtains
a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with lactose, dry granulation obtains b；
7. 5., 6. particle and magnesium stearate that step is obtained mix, direct tablet compressing is to get containing Suo Malu
The oral slow-releasing preparation of peptide.
The measurement of 11 vitro cumulative release of embodiment
The bag filter (8000-14000) that clip length is about 5cm, is put into the beaker for filling suitable quantity of water, heating is boiled
5min (timing since boiling water), bag filter one end after boiling are tightened with filament, leak detection.It is carried out using dynamic dialysis method
The measurement of vitro cumulative release.
Precision claims in the oral slow-releasing preparation 40mg merging bag filters of the peptide containing Suo Malu of the preparation of embodiment 1,3,7,10, adds
Enter 2mL PBS buffer solution (0.1M, pH=7.4 contain 0.02% sodium azide), sealing is placed in equipped with 48mL PBS buffer solution
It in conical flask with cover, is put into the water bath with thermostatic control shaking table of (37.0 ± 0.5) DEG C, is 100rmin with rotating speed-1Speed shaking, point
Not in 0.25,0.5,1,2,4,8,12,5mL is respectively taken out for 24 hours, while adding the PBS buffer solution of the fresh equality of temperature of equivalent, with ultraviolet point
Light photometer measures absorbance, calculates cumulative release percentage, and it is as shown in Figure 1 to draw release profiles.
The oral slow-releasing preparation that the release profiles of Fig. 1 can be seen that the peptide containing Suo Malu of the present invention can be held in 24 hours
Continue stable release drug, ensures the stabilization of blood concentration, reached the purpose of the present invention.
The oral slow-releasing preparation of the peptide containing Suo Malu made from Example 2,4,5,6,8,9 carries out drug release determination, as a result
It is close with the result that embodiment 1,3,7,10 measures, show the oral slow of the peptide containing Suo Malu that embodiment 2,4,5,6,8,9 provides
Release formulation equally has apparent slow releasing function, ensures the stabilization of blood concentration, has reached the purpose of the present invention.
Claims (10)
1. a kind of oral slow-releasing preparation of peptide containing Suo Malu, which is characterized in that it is mainly by containing Suo Malu peptide medicine active constituents
Sustained-release micro-spheres and other pharmaceutically acceptable auxiliary materials be directly compressed into the effigurate tablet of tool and form, wherein it is described
Sustained-release micro-spheres include the peptide containing Suo Malu active constituents of medicine, slow releasing carrier material, other pharmaceutically acceptable auxiliary materials；Its
In：
1. by mass percentage, the active constituents of medicine of the peptide containing Suo Malu is 1.2%~10%, slow releasing carrier material 60%
~90%, other pharmaceutically acceptable auxiliary materials are 5%~30%.
2. sustained-release micro-spheres are prepared by W1/O/W2 multi-emulsion methods.
2. the oral slow-releasing preparation of the peptide according to claim 1 containing Suo Malu, which is characterized in that the peptide containing Suo Malu
Active constituents of medicine be Suo Malu peptides and with Suo Malu peptides sulfonylureas with synergy, biguanides or thiazolidinediones
Hypoglycemic medicine.
3. according to claim 2 and Suo Malu peptides hypoglycemic medicine with synergy, which is characterized in that the sulfonylurea
Class antidiabetic drug can be selected from gliclazide, Glimepiride or gliquidone；The biguanides can be selected from melbine；It is described
Thiazolidinediones antidiabetic drug can be selected from Ciglitazone, Pioglitazone or Rosiglitazone.
4. the oral slow-releasing preparation of the peptide according to claim 1 containing Suo Malu, which is characterized in that Suo Malu peptides with association
The mass ratio of the hypoglycemic medicine of same-action is 1:1~5:1.
5. the oral slow-releasing preparation of the peptide according to claim 1 containing Suo Malu, which is characterized in that the slow releasing carrier material
It is one or more in cellulose acetate, ethyl cellulose, polyethylene, polymethyl methacrylate.
6. the oral slow-releasing preparation of the peptide according to claim 1 containing Suo Malu, which is characterized in that the sustained-release micro-spheres Chinese medicine
Other acceptable auxiliary materials are drug release regulator on, and the drug release regulator is in polyethylene glycol, Tween-80, mannitol
It is one or more.
7. the oral slow-releasing preparation of the peptide according to claim 1 containing Suo Malu, which is characterized in that the oral slow-releasing preparation
In further include N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate, filler, adhesive and lubricant.
8. the oral slow-releasing preparation of the peptide according to claim 7 containing Suo Malu, which is characterized in that the filler can be selected from
It is one or more in lactose, pregelatinized starch, microcrystalline cellulose；Described adhesive can be selected from sodium carboxymethylcellulose, hydroxypropyl
It is one or more in base cellulose；The lubricant can be selected from one kind or more in superfine silica gel powder, magnesium stearate, talcum powder
Kind.
9. a kind of method for the oral slow-releasing preparation preparing the peptide containing Suo Malu described in any one of claim 1-8, including with
Lower step：
1. weighing active constituents of medicine, slow releasing carrier material and the drug release regulator of the peptide containing Suo Malu respectively according to recipe quantity；It will
The active constituents of medicine of drug release regulator and the peptide containing Suo Malu is dissolved in the water, as inner aqueous phase W1；Slow-released carrier is dissolved in organic
In solvent, as organic phase O；Polyvinyl alcohol is soluble in water, as outer aqueous phase W2；
2. inner aqueous phase W1 is added in organic phase O, ultrasonic emulsification forms uniform colostrum W1/O；
3. colostrum W1/O is added in outer aqueous phase W2, ultrasonic emulsification forms emulsion W1/O/W2；
4. emulsion W1/O/W2 removes organic solvent by stirring to volatilize, after isolating solid, wash with water 3 times, 40~60 DEG C dry
Up to the sustained-release micro-spheres of the peptide containing Suo Malu after dry；
5. the sustained-release micro-spheres of the step 4. peptide containing Suo Malu obtained are mixed with filler and/or adhesive, dry granulation obtains
a；
6. N- (8- (2- (2-hydroxybenzoyl)s) amino) caprylate is mixed with lubricant and/or filler, dry granulation obtains b；
7. 5., 6. particle and lubricant that step is obtained mix, direct tablet compressing to get the peptide containing Suo Malu mouth
Take sustained release preparation.
10. preparation method according to claim 8, which is characterized in that the organic solvent is selected from diformazan chlorine alkane, acetic acid
Ethyl ester or acetone；It is preferred that diformazan chlorine alkane.
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| CN112274633A (en) * | 2020-09-16 | 2021-01-29 | 广州新济薇娜生物科技有限公司 | Somalutide blood sugar-reducing and weight-reducing microneedle patch and preparation method and application thereof |
| CN113018277A (en) * | 2019-12-25 | 2021-06-25 | 丽珠医药集团股份有限公司 | Sustained-release preparation for injection and preparation method thereof |
| CN113117050A (en) * | 2021-05-06 | 2021-07-16 | 合肥天汇孵化科技有限公司 | Polypeptide composition and application thereof |
| CN113440604A (en) * | 2021-06-24 | 2021-09-28 | 浙江泽瑞生物医药有限公司 | Oral sustained-release tablet of somaglutide for effectively inhibiting blood sugar and preparation method thereof |
| CN114225012A (en) * | 2021-12-16 | 2022-03-25 | 浙江湃肽生物有限公司 | Method for measuring bioactivity of somaglutide |
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Application publication date: 20181002 |