CN108464972A - A kind of anti-pulmonary hypertension oral tablet and preparation method thereof containing Snopori - Google Patents
A kind of anti-pulmonary hypertension oral tablet and preparation method thereof containing Snopori Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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Abstract
The present invention provides a kind of oral tablet of anti-pulmonary hypertension and preparation method thereof, and raw material forms by weight includes：650 800 parts of microcrystalline cellulose, 400 600 parts of lactose monohydrate, 50 250 parts of pregelatinized starch, 50 250 parts of cornstarch, 3 15 parts of stearic acid, 500 800 parts of monohydrate Snopori crystal.At 0 10 DEG C, raw material, the control of auxiliary material moisture are made in 5% tabletting.Tablet obtained is rapid-action, can control the pulmonary arterial pressure of patient rapidly, longer, toxic side effect is small, stable dosage forms.
Description
Technical field
The present invention relates to drug field, more particularly, to a kind of anti-pulmonary hypertension oral tablet containing Snopori and
Preparation method.
Background technology：
Pulmonary hypertension (pulmonary arterial hypertension, PAH), is mainly increased by pulmonary artery tension
The caused pulmonary vascular resistance of vascular remodeling joint is summed it up to increase, by pulmonary artery pressure increase with the characteristics of, the state of an illness carry out sexual development
A kind of lethal angiocardiopathy.Clinical most common onset symptoms are：Shortness of breath, weak, pectoralgia, spitting of blood after activity；Part
Patient can seriously affect the daily life of patient when there is dyshaemia or arrhythmia cordis along with performances such as dizziness, syncopes, and one
A little extremely tiny injuries are all likely that there are fatal danger.
It is shown according to update, PAH patient about 100,000,000 people caused by the whole world is influenced by a variety of causes, therefore PAH has become
To influence one of the major disease of human health.It for the epidemic of PAH, is not quite similar between various countries, China PAH suffers from
Person is with congenital heart disease correlation PAH ratio highests, and China PAH registration studies congenital heart disease correlations PAH is accounted within 2008 to 2011
43%, idiopathic PAH are that 35%, CTD correlations PAH accounts for 19%.With the registration studies in area, congenital heart disease is related for other countries
PAH proportions are 10%~23%.PAH can be by left heart disease, congenital heart disease, Hypoxic lesion, pulmonary thromboembolism
Etc. diseases induce：
1) pulmonary hypertension that left heart disease induces accounts for about the 78.8% of whole pulmonary hypertensions.Hypertension, diabetes, hat
The later stage of the diseases such as worry often concurrent cardiac insufficiency, further results in pulmonary hypertension；
2) pulmonary hypertension that congenital heart disease (intracardiac shunt causes) can induce；
3) pulmonary hypertension caused by connective tissue disease, including various rheumatism, atrophic diseases.It should be first when treatment
Use hormone and immunosuppressor；
4) hypoxic pulmonary hypertension：Chronic bronchitis, pulmonary emphysema, Chronic Obstructive Pulmonary Disease, bronchiectasis, lung
The diseases such as tuberculosis also result in pulmonary vascular resistance increase, pulmonary hypertension and right heart failure.Caused by Chronic Obstructive Pulmonary Disease
Anoxic is merit attention the problem of；Another aspect High Altitude Pulmonary Hypertension is external rare but common in China.These
Due to alveolar hypoxia hypoxic pulmonary vasoconstriction then occurs for patient, and pulmonary arterial pressure increases.
5) chronic thromboembolic pulmonary hypertension.These causes of disease occupy 99% or more pulmonary hypertension group.
Domestic alternative drug includes at present：
1) prostacyclin class drug：Such as Wan Tawei, inhaled iloprost, injection Epoprostenol, SELEXING；
2) endothelin 1 receptor antagonists：Bosentan, ambrisentan etc.；
3) phosphodiesterase 5 inhibitor：Such as relatively inexpensive drug of silaenafil, Tadalafei；
4) vasodilator：Such as angiotensin converting enzyme inhibitor (ACEI), calcium channel blocker.
5)sGC：The western croak of Leo
Snopori (S nitrosocaptopril, S-nitrosocaptopril, CapNO；Patent of invention number
ZL97101919.3；Chemical 1.1 class medicines) it is the new drug for having both sGC targeting and vasodilator double action.Earliest documents report
Road and compound patent appear in 1988~1989 years, and it is chemical parent nucleus that it, which is with Cap, transform the sulfydryl (- SH) of Cap as Asia
A kind of not only releasable NO in vivo that nitryl sulfydryl (- SNO) is formed afterwards, but also the dual function chemical combination with ACEI properties
Object.According to the biochemical reaction formula of RSNO class compounds, decomposition product is the oxidation of RSSR (such as Cap-Cap, Cap-SR) and NO, NO
Final product is NO2 and NO3.Snopori is one kind with sGC (soluble guanylate cyclase, soluble guanylate ring
Change enzyme) be target spot new mechanism drug.Its captopril parent nucleus with ACEI pharmacological action with duration expansion blood vessel,
Reduce pulmonary hypertension；It is smooth that there is its NO group selectivity to reduce pulmonary vascular resistance, pulmonary arterial pressure and slight loose respiratory tract
Flesh to reduce resistance of respiratory tract, increase pulmonary circulation blood flow, improve lung ventilation/blood flow than effect；In addition, NO groups may be used also
The generated vaso-excitor material of facedown inhibits platelet aggregation, reduces cholesterolemia and prevention of arterial atherosis, slightly
Inhibit gastrointestinal smooth muscle.
Invention content
It is an object of the present invention to provide a kind of oral tablets of anti-pulmonary hypertension, and the tablet is rapid-action, can it is rapid,
The pulmonary arterial pressure of patient is controlled longer, and toxic side effect is small, stable dosage forms.Another purpose, which is to provide, a kind of preparing anti-pulmonary artery
The method of high pressure oral tablet, to complete the production of the oral tablet under real existing frequently-used working condition.
To achieve the goals above, present invention employs following technical solutions.
This anti-hypertension oral tablet is made of the raw material of following components by weight percent：650-800 parts of microcrystalline cellulose, lactose
400-600 parts of monohydrate (Lactose Monohydrate), 50-250 parts of pregelatinized starch, 50-250 parts of cornstarch,
3-15 parts of stearic acid, 500-800 parts of monohydrate Snopori crystal.
The method for preparing the anti-pulmonary hypertension oral tablet is included the following steps using above-mentioned raw materials component：
(1) it takes microcrystalline cellulose, lactose monohydrate, pregelatinized starch, cornstarch, be uniformly mixed, incorporation time 30-
50min obtains auxiliary material mixture A；
(2) the auxiliary material mixture A for taking step (1) to obtain is added stearic acid, is sufficiently mixed and grinds 20-40min, obtain
Auxiliary material mixture B；
(3) it takes auxiliary material mixture B to be fully ground with monohydrate Snopori crystal and mixes 10-20min, cross 20 mesh sieve,
Obtain Snopori tablet mixture
(4) by the Snopori tablet mixture, tablet press machine compression moulding is used in combination.
Preferably, the step (3) and step (4) temperature should be controlled at 0-10 DEG C, and control moisture within 5%.
Wherein, selected monohydrate Snopori is the chemical combination of crystalline compounds and other crystal forms with following features
Object：
Common name：Snopori
The Chinese phonetic alphabet：Sinuopuli
English name：S-nitrosocaptopril
CAS：122130-63-6
Chinese chemical name：
1- ((2S) -2- methyl -3- nitroso mercapto -1- oxopropyls)-L-PROLINE monohydrate
English language Chemical name：
1-(2-methyl-3-nitrosulfanyl-propionyl)-pyrrolidine-2-carboxylic acid
Chemical constitution：
Molecular weight：264.28300
Molecular formula：C9H16N2O5S
(S nitrosocaptopril, S-nitrosocaptopril, CapNO are to have both sGC targetings and blood vessel to Snopori
The new drug of expander double action.It is chemical parent nucleus that it, which is with Cap, by the sulfydryl (- SH) of Cap transform as nitrosyl sulfydryl (-
SNO a kind of not only releasable NO in vivo) formed afterwards, but also the dual function compound with ACEI properties.According to RSNO
The biochemical reaction formula of class compound, decomposition product, which is the oxidation final product of RSSR (such as Cap-Cap, Cap-SR) and NO, NO, is
NO2 and NO3.Snopori is that one kind is with sGC (soluble guanylate cyclase, soluble guanylate cyclase)
The drug of the new mechanism of target spot.Pharmacological action of its captopril parent nucleus with ACEI is with duration expansion blood vessel, reduction lung
Arterial hypertension；Its NO group have selectivity reduce pulmonary vascular resistance, pulmonary arterial pressure and slight loose airway smooth muscle to
Reduce resistance of respiratory tract, increase pulmonary circulation blood flow, improve lung ventilation/blood flow than effect；In addition, NO groups can also be directly right
Resist generated vaso-excitor material, inhibits platelet aggregation, reduces cholesterolemia and prevention of arterial atherosis, slightly inhibit stomach
Intestinal smooth muscle.
Beneficial effects of the present invention：
The oral tablet preparation that the present invention contains Snopori anti-pulmonary hypertension requires content accurate in quality, weight
Difference is small, and disintegration time or dissolution rate meet regulation, and hardness is appropriate, and appearance is beautiful, and color and luster is good, meets sanitary inspection standard,
Provide that storage period property is stablized.Dosage is accurate, and stable in physicochemical property, storage period are longer, use, transport and easy to carry, price
It is low, yield is high etc., simple for process, favorable reproducibility, be easy to industry's enlarging production.
Description of the drawings
Fig. 1 Snopori oral tablets.
Specific implementation method
With reference to embodiment, the present invention is described in further detail, to enable those skilled in the art with reference to specification
Word can be implemented according to this.
Embodiment 1
CapNO·H2O Formulations (200g)：
This anti-pulmonary hypertension oral tablet containing Snopori is made of the raw material of following components by weight percent：Microcrystalline cellulose
Plain 700g, lactose monohydrate 550g, pregelatinized starch 100g, cornstarch 100g, stearic acid 5g, monohydrate Snopori knot
Brilliant 545g.
The method that the oral tablet of the anti-pulmonary hypertension is prepared using above-mentioned raw materials component, is included the following steps：
(1) microcrystalline cellulose is taken, lactose monohydrate, pregelatinized starch, cornstarch is uniformly mixed, incorporation time
40min obtains auxiliary material mixture A.
(2) auxiliary material mixture A is taken, stearic acid is added, is sufficiently mixed and grinds 35min, obtain auxiliary material mixture B.
(3) it takes auxiliary material mixture B to be fully ground with monohydrate Snopori crystal and mixes 15min, cross 20 mesh sieve, obtain
Snopori tablet mixture.
(4) the Snopori tablet mixture is taken, with tablet press machine compression moulding.
(5) temperature in whole manufacturing process should be controlled at 10 DEG C, and control moisture within 5%.
Measure single 0.1998 ± 0.0043g of tablet weight；
The technical program is prepared into disintegration time limited of the oral tablet in 37 DEG C, 900mL diluted hydrochloric acid aqueous solutions and collapses completely
Dissolution rate when solution.
As a result：Snopori oral tablet complete disintegration time limited is 4-6 minutes, and dissolution rate when being disintegrated completely is 86%-
91%.
Embodiment 2
CapNO·H2O Formulations (200g)：
This anti-pulmonary hypertension oral tablet containing Snopori is made of the raw material of following components by weight percent：Microcrystalline cellulose
Plain 650g, lactose monohydrate 600g, pregelatinized starch 100g, cornstarch 100g, stearic acid 5g, monohydrate Snopori
Crystallize 545g.
The method for preparing the anti-pulmonary hypertension oral tablet is included the following steps using above-mentioned raw materials component：
(1) microcrystalline cellulose is taken, lactose monohydrate, pregelatinized starch, cornstarch is uniformly mixed, incorporation time
30min obtains auxiliary material mixture A.
(2) auxiliary material mixture A is taken, stearic acid is added, is sufficiently mixed and grinds 40min, obtain auxiliary material mixture B.
(3) it takes auxiliary material mixture B to be fully ground with monohydrate Snopori crystal and mixes 20min, cross 20 mesh sieve, obtain
Snopori tablet mixture.
(4) the Snopori tablet mixture is taken, with tablet press machine compression moulding.
(5) temperature in whole manufacturing process should be controlled at 4 DEG C, and control moisture within 5%.
Measure single 0.1993 ± 0.0024g of tablet weight；
The technical program is prepared into disintegration time limited of the oral tablet in 37 DEG C, 900mL diluted hydrochloric acid aqueous solutions and collapses completely
Dissolution rate when solution.
As a result：Snopori oral tablet complete disintegration time limited is 4-6 minutes, and dissolution rate when being disintegrated completely is 85%-
91%.
Embodiment 3
CapNO·H2O Formulations (200g)：
This anti-pulmonary hypertension oral tablet containing Snopori is made of the raw material of following components by weight percent：Microcrystalline cellulose
Plain 800g, lactose monohydrate 400g, pregelatinized starch 150g, cornstarch 140g, stearic acid 5g, monohydrate Snopori knot
Brilliant 505g.
The method that the oral tablet of the anti-pulmonary hypertension is prepared using above-mentioned raw materials component, is included the following steps：
(1) microcrystalline cellulose is taken, lactose monohydrate, pregelatinized starch, cornstarch is uniformly mixed, incorporation time
45min obtains auxiliary material mixture A.
(2) it takes auxiliary material mixture A, stearic acid to be sufficiently mixed and grind 30min, obtains auxiliary material mixture B.
(3) it takes auxiliary material mixture B to be fully ground with monohydrate Snopori crystal and mixes 15min, cross 20 mesh sieve, obtain
Snopori tablet mixture.
(4) by the Snopori tablet mixture, tablet press machine compression moulding is used in combination.
(5) temperature in whole manufacturing process should be controlled at 0 DEG C, and control moisture within 5%.
Measure single 0.2006 ± 0.0018g of tablet weight；
The technical program is prepared into disintegration time limited of the oral tablet in 37 DEG C, 900mL diluted hydrochloric acid aqueous solutions and collapses completely
Dissolution rate when solution.
As a result：Snopori oral tablet complete disintegration time limited is 4-6 minutes, and dissolution rate when being disintegrated completely is 87%-
93%.
Embodiment 4
CapNO·H2O Formulations (200g)：
This anti-pulmonary hypertension oral tablet containing Snopori is made of the raw material of following components by weight percent：Microcrystalline cellulose
Plain 600g, lactose monohydrate 400g, pregelatinized starch 50g, cornstarch 150g, stearic acid 10g, monohydrate Snopori knot
Brilliant 790g.
The method that the oral tablet of the anti-pulmonary hypertension is prepared using above-mentioned raw materials component, is included the following steps
(1) microcrystalline cellulose is taken, lactose monohydrate, pregelatinized starch, cornstarch is uniformly mixed, incorporation time
30min obtains auxiliary material mixture A.
(2) it takes auxiliary material mixture A, stearic acid to be sufficiently mixed and grind 25min, obtains auxiliary material mixture B.
(3) it takes auxiliary material mixture B to be fully ground with monohydrate Snopori crystal and mixes 10min, cross 20 mesh sieve, obtain
Snopori tablet mixture.
(4) by the Snopori tablet mixture, tablet press machine compression moulding is used in combination.
(5) temperature in whole manufacturing process should be controlled at 4 DEG C, and control moisture within 5%.
Measure single 0.2009 ± 0.0041g of tablet weight；
The technical program is prepared into disintegration time limited of the oral tablet in 37 DEG C, 900mL diluted hydrochloric acid aqueous solutions and collapses completely
Dissolution rate when solution.
As a result：Snopori oral tablet complete disintegration time limited is 4-6 minutes, and dissolution rate when being disintegrated completely is 89%-
94%.
Embodiment 5
CapNO·H2O Formulations (200g)：
This anti-pulmonary hypertension oral tablet containing Snopori is made of the raw material of following components by weight percent：Microcrystalline cellulose
Plain 70g, lactose monohydrate 55g, pregelatinized starch 10g, cornstarch 10g, stearic acid 0.5g, monohydrate Snopori crystal
54.5g。
The method that the oral tablet of the anti-pulmonary hypertension is prepared using above-mentioned raw materials component, is included the following steps：
(1) microcrystalline cellulose is taken, lactose monohydrate, pregelatinized starch, cornstarch is uniformly mixed, incorporation time
30min obtains auxiliary material mixture A.
(2) auxiliary material mixture A is taken, stearic acid is added, is sufficiently mixed and grinds 20min, obtain auxiliary material mixture B.
(3) it takes auxiliary material mixture B to be fully ground with monohydrate Snopori crystal and mixes 10min, cross 20 mesh sieve, obtain
Snopori tablet mixture.
(4) the Snopori tablet mixture is taken, with tablet press machine compression moulding.
(5) temperature in whole manufacturing process should be controlled at 4 DEG C, and control moisture within 5%.
Measure single 0.1989 ± 0.0069g of tablet weight；
The technical program is prepared into disintegration time limited of the oral tablet in 37 DEG C, 900mL diluted hydrochloric acid aqueous solutions and collapses completely
Dissolution rate when solution.
As a result：Snopori oral tablet complete disintegration time limited is 4-6 minutes, and dissolution rate when being disintegrated completely is 84%-
89%.
Embodiment 6
CapNO·H2O Formulations (200g)：
This anti-pulmonary hypertension oral tablet containing Snopori is made of the raw material of following components by weight percent：Microcrystalline cellulose
Plain 70g, lactose monohydrate 50g, pregelatinized starch 10g, cornstarch 10g, stearic acid 1g, monohydrate Snopori crystal
59g。
The method that the oral tablet of the anti-pulmonary hypertension is prepared using above-mentioned raw materials component, is included the following steps：
(1) microcrystalline cellulose is taken, lactose monohydrate, pregelatinized starch, cornstarch is uniformly mixed, incorporation time
50min obtains auxiliary material mixture A.
(2) it takes auxiliary material mixture A, stearic acid to be sufficiently mixed and grind 40min, obtains auxiliary material mixture B.
(3) it takes auxiliary material mixture B to be fully ground with monohydrate Snopori crystal and mixes 20min, cross 20 mesh sieve, obtain
Snopori tablet mixture.
(4) the Snopori tablet mixture is taken, with tablet press machine compression moulding.
(5) temperature in whole manufacturing process should be controlled at 0 DEG C, and control moisture within 5%.
Measure single 0.1995 ± 0.0055g of tablet weight；
The technical program is prepared into disintegration time limited of the oral tablet in 37 DEG C, 900mL diluted hydrochloric acid aqueous solutions and collapses completely
Dissolution rate when solution.
As a result：Snopori oral tablet complete disintegration time limited is 4-6 minutes, and dissolution rate when being disintegrated completely is 88%-
93%.
Embodiment 7
Embodiment 1 is containing Snopori monohydrate tablets to the pharmacodynamic action of pulmonary hypertension model rat：
Monocrotaline intraperitoneal injection (50mg/kg) modeling successful pulmonary hypertension (PAH) rat is divided into 2 groups, respectively
For physiological saline blank control group (9), Snopori group (7), gastric infusion and healthy rat (9) totally 3 is implemented daily
Conventinal breeding 30 days, the rat of wherein Snopori group give the physiological saline that 1 piece/pcs/day of tablet is made in example 1 to group together
Lysate.As a result none death of health group rat, the blank control group PAH rats of physiological saline gavage are reduced to 1 by 9,
Snopori group PAH rats are reduced to 5 by 7.To the healthy rat, blank group control group, Snopori group of survival rats
Carry out echocardiogram measurement, physiologic measurement.It was found that the rat right ventricular internal diameter (RVID) of blank group and Snopori group point
Not Wei 1.78 ± 0.05mm and 1.75mm, healthy rat be 1.52 ± 0.03mm be not present significant changes；Cardiac output
(CO) blank group is 9.82mL/min, and Snopori group has for the cardiac output of rat after 12.73 ± 0.10ml/min medications
It is obviously improved；Tricuspid valve systole phase displacement (TAPSE), Snopori group be 1.33 ± 0.07mm, blank group 1.11mm,
Health group increases for tricuspid valve systole phase displacement after 1.42 ± 0.05mm medications；Right systolic pressure (RVSP) blank group is
31Hg Snopori groups significantly reduce for 25 ± 1mmHg systolic pressures；Pulmonary vascular resistance (PVR) blank group is 78dyn*s/cm5, this
Promise Puli group is 55 ± 278dyn*s/cm5Pulmonary vascular resistance significantly reduces；Art pO2 (PO2) blank group be 133 ±
5mmHg, Snopori group are 152 ± 9mmHg, and partial pressure of oxygen is obviously improved.It dissects rat cadavers to find, Snopori group rat chest
Chamber hydrops average external volume is respectively 0.5mL；In terms of average right ventricle performance figure (RVMI), blank control group, Snopori group
Respectively 70.8%, 35.2%.The above result shows that Snopori monohydrate tablets significantly improve the survival rate of PAH rats,
Pulmonary artery pressure (P ＜ 0.05) is reduced, pleural effusion (P ＜ 0.05) is reduced, mitigates right heart burden (P ＜ 0.05), to pulmonary artery
High pressure rat has significant therapeutic effect.
The foregoing is merely presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with
Modification should all belong to the covering scope of the present invention.
Claims (6)
1. a kind of oral tablet of anti-pulmonary hypertension, which is characterized in that the oral tablet include Snopori function at
Point.
2. a kind of oral tablet of anti-pulmonary hypertension according to claim 1, which is characterized in that the Snopori packet
Compound containing Snopori and other Snopori crystalline hydrates.
3. a kind of oral tablet of anti-pulmonary hypertension according to claim 1, which is characterized in that the Snopori is
Monohydrate Snopori crystal.
4. a kind of oral tablet of anti-pulmonary hypertension according to claim 1, which is characterized in that the oral tablet
It is made of the raw material of following components by weight percent：650-800 parts of microcrystalline cellulose, 400-600 parts of lactose monohydrate, pregelatinized starch
50-250 parts, 50-250 parts of cornstarch, 3-15 parts of stearic acid, 500-800 parts of monohydrate Snopori crystal.
5. a kind of preparation method of anti-pulmonary hypertension oral tablet as described in claim 1, it is characterised in that：Including following
Step：
(1) it takes microcrystalline cellulose, lactose monohydrate, pregelatinized starch, cornstarch, be uniformly mixed, incorporation time 30-
50min obtains auxiliary material mixture A；
(2) the auxiliary material mixture A for taking step (1) to obtain is added stearic acid, is sufficiently mixed and grinds 20-40min, obtain auxiliary material
Mixture B；
(3) it takes auxiliary material mixture B to be fully ground with monohydrate Snopori crystal and mixes 10-20min, cross 20 mesh sieve, obtain
Snopori tablet mixture；
(4) by the Snopori tablet mixture, tablet press machine compression moulding is used in combination.
6. the preparation method of anti-pulmonary hypertension oral tablet according to claim 5, which is characterized in that in manufacturing process
Temperature should be controlled at 0-10 DEG C, and Snopori tablet mixture moisture controls within 5%.
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Application publication date: 20180831 |