CN102119930A - Olmesartan medoxomil tablets and preparation method thereof - Google Patents
Olmesartan medoxomil tablets and preparation method thereof Download PDFInfo
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- CN102119930A CN102119930A CN 201010224565 CN201010224565A CN102119930A CN 102119930 A CN102119930 A CN 102119930A CN 201010224565 CN201010224565 CN 201010224565 CN 201010224565 A CN201010224565 A CN 201010224565A CN 102119930 A CN102119930 A CN 102119930A
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Abstract
The invention discloses olmesartan medoxomil tablets and a preparation method thereof. The cores of 1000 olmesartan medoxomil tablets comprise 20g of olmesartan medoxomil, 60-95g of lactose (1), 30g of lactose (2), 45-50g of microcrystalline cellulose, 5g of polyvinylpyrrolidone K30 (PVPK30), 8g of low-substituted hydroxypropyl cellulose (L-HPC), 1g of magnesium stearate and an ethanol water solution for preparing a soft material. The invention solves the problem that no olmesartan medoxomil tablets can be used clinically at present.
Description
Technical field
The present invention relates to medicine field, in particular to a kind of olmesartan medoxomil sheet and preparation method.
Background technology
Death toll it is said also higher than the summation of other 7 kinds of underlying cause of death diseases (comprising that cancer and AIDS/HIV infect) due to the cardiovascular diseases.Hypertension is the most popular and become a problem of new drug development merchant emphasis among the cardiovascular diseases.F﹠amp; S market research agency estimates that the growth of hypertension therapeutic will stimulate the expansion in cardiovascular drug market, the world, will contribute about 10 percentage points for the year overall growth rate of cardiovascular drug by 2002.Add that pharmacy industry faces huge chance to demand effective, the medicine that has no side effect.
Antihypertensive claims depressor again, means effectively to bring high blood pressure down the medicine of treatment vascular hypertension.Position according to main effect can be divided into multiclass, and wherein Yan Jiu focus is (1) calcium antagonist: nifedipine, nimodipine, nitrendipine, non-promise Horizon, bepridil.(2) angiotensin converting enzyme inhibitor; (3) Angiotensin.Olmesartan medoxomil is one of state-of-the art Angiotensin.The effect of the Olmesartan pair AT2 receptor not too relevant with cardiovascular system than AT1 receptor a little less than 12500 times.Because Olmesartan does not suppress ACE, therefore it does not influence the degraded of Kallidin I, to the not influence of effect of Kallidin I, the serum potassium level do not had influence.
The olmesartan medoxomil sheet can be used for each phase hypertension.But also there is not spendable olmesartan medoxomil sheet clinically at present.The preparation method of any olmesartan medoxomil sheet is not disclosed in the prior art in addition, yet.
Summary of the invention
Propose the present invention at the problem that does not have spendable clinically olmesartan medoxomil sheet in the prior art, for this reason, main purpose of the present invention is to provide a kind of olmesartan medoxomil sheet and preparation method, to address the above problem.
To achieve these goals, according to an aspect of the present invention, a kind of olmesartan medoxomil sheet is provided, and the label of 1000 olmesartan medoxomil sheets comprises: olmesartan medoxomil 20g, lactose 1. 60g to 95g, lactose 2. 30g, microcrystalline Cellulose 45g to 50g, 5g PVPK30, low-substituted hydroxypropyl cellulose L-HPC 8g, magnesium stearate 1g and be used to make the ethanol water of soft material.
Preferably, the coating solution of described 1000 olmesartan medoxomil sheets comprises: coating powder 5.1g and 64ml ethanol water.
Preferably, described ethanol water is 50% ethanol water.
Preferably, 1. described lactose is 60g.
Preferably, described microcrystalline Cellulose is 45g.
To achieve these goals, according to another fermentation of the present invention, a kind of preparation method of above-mentioned olmesartan medoxomil sheet also is provided, comprise: lactose 2., microcrystalline Cellulose, PVPK30 and L-HPC all cross 80 mesh sieves, with olmesartan medoxomil and lactose 1. mixed grinding cross 100 after 2 hours, 120 or 160 mesh sieves, to contain olmesartan medoxomil powder and lactose 2. by recipe quantity, microcrystalline Cellulose, PVPK30, behind the L-HPC mix homogeneously, with ethanol water system soft material, granulate with 24 mesh sieves, the oven dry, behind the 22 mesh sieve granulate, add the magnesium stearate mixing of recipe quantity after, stamping is put into the coating pan coating with the gained sheet.
Preferably, olmesartan medoxomil and lactose 1. mixed grinding cross 120 mesh sieves after 2 hours.
Preferably, use 50 ℃ of oven dry.
Preferably, with φ 8mm stamping.
Preferably, the gained sheet is put into coating pan coating weightening finish 2-3%.
By the present invention, solved the problem that does not have spendable clinically olmesartan medoxomil sheet at present.
Description of drawings
Accompanying drawing described herein is used to provide further understanding of the present invention, constitutes the application's a part, and illustrative examples of the present invention and explanation thereof are used to explain the present invention, do not constitute improper qualification of the present invention.In the accompanying drawings:
Fig. 1 is the preparation technology's flow chart according to the olmesartan medoxomil sheet of the embodiment of the invention.
The specific embodiment
Need to prove that under the situation of not conflicting, embodiment and the feature among the embodiment among the application can make up mutually.Describe the present invention below with reference to the accompanying drawings and in conjunction with the embodiments in detail.
The tablet of olmesartan medoxomil sheet can have 5 milligrams, 20 milligrams, 40 milligrams three kinds of specifications, carries out the administration individuation to make things convenient for patient according to the state of an illness.In following enforcement with
One, prescription
Selecting 20mg is that specification is studied.By research, determine that this product prescription is:
1, label prescription:
Olmesartan medoxomil 20g
Lactose is 60g 1.
Lactose is 30g 2.
Microcrystalline Cellulose 45g
PVPK30 5g
Low-substituted hydroxypropyl cellulose (L-HPC) 8g
50% ethanol water is an amount of
Magnesium stearate 1g
Make 1000
2, coating fluid prescription (1000):
Coating powder 5.1g
50% ethanol 64ml
Two, technology
Fig. 1 is the preparation technology's flow chart according to the olmesartan medoxomil sheet of the embodiment of the invention, as shown in Figure 1, lactose 2., microcrystalline Cellulose, PVPK30, L-HPC all crosses 80 mesh sieves, with principal agent and lactose 1. mixed grinding cross 120 mesh sieves after 2 hours, to contain principal agent powder and lactose 2. by recipe quantity, microcrystalline Cellulose, PVPK30, behind the L-HPC mix homogeneously, with 50% ethanol water system soft material, granulate with 24 mesh sieves, 50 ℃ of oven dry, behind the 22 mesh sieve granulate, after adding the magnesium stearate mixing of recipe quantity, with φ 8mm stamping, with the gained sheet put into the coating pan coating increase weight to 2-3% promptly.
Three, prescription screening
The result shows: prescription I dissolution very low (on average being about 13%); Prescription II principal agent dissolution after 160 orders sieve increases (being about 40%), but still lower; In prescription III and the IV principal agent and part lactose through mixed grinding after 2 hours dissolution reach more than 80%, and prescription and prescription III are relatively, it is smooth that prescription IV gained sheet shows, mobility of particle is good, hardness is suitable, so select the prescription IV finally to write out a prescription as this product.
Five, the influence factor of pilot sample test
Get this product pilot sample (lot number: 030819), remove outer package, 30 every part, place the glass dish of having weighed respectively.Place 40 ℃ of baking ovens, 60 ℃ of baking ovens respectively, fill saturated nacl aqueous solution exsiccator, fill the exsiccator of saturated potassium nitrate solution and the lighting box of 4500Lx, placed 10 days, weigh in sampling in the 5th and 10 day, and inspection appearance character, related substance, dissolution and content, the results are shown in Table 1, relevant collection of illustrative plates is seen accompanying drawing.
Table 1 olmesartan medoxomil sheet influence factor result of the test
The result shows that the olmesartan medoxomil sheet is under influence factor's experimental condition, and except that high temperature was slightly weightless, high humility slightly increases weight, other every indexs had no significant change.As seen this product is stable under influence factor's experimental condition, and it is feasible to write out a prescription.
The Olmesartan pharmacokinetics
Ordinary circumstance
Olmesartan medoxomil is through possessing biological activity rapidly and behind the generation of the steatolysis fully Olmesartan after the gastrointestinal absorption.Olmesartan is eliminated with the two-phase formula, and about 13 hours of half-life is eliminated at the end mutually.With 320 milligrams single oral dose administrations or high to 80 milligrams dosage repeatedly during oral administration pharmacokinetics present linear feature.
The plasma concentration of Olmesartan reached stable state after the administration in 3～5 days once a day, did not produce and accumulated.The absolute bioavailability of Olmesartan is 26% approximately.In the time of 1～3 hour, reach peak serum concentration (Cmax) after taking medicine.Food does not influence the bioavailability of Olmesartan.
Metabolism and drainage
After olmesartan medoxomil was absorbed rapidly and changes into Olmesartan fully, Olmesartan was not in fact by further metabolism.The blood plasma total body clearance of Olmesartan is 1.3L/h, and the kidney clearance rate is 0.6L/h.About amount of being absorbed of 35%～50% is detected in urine, and remainder is by feces or bile excretion.
Distribute
The distribution volume of Olmesartan is 17 liters approximately.The combination rate height (99%) of Olmesartan and plasma protein is impermeablely gone into erythrocyte.When giving the medicine of recommended amounts, Olmesartan and plasma protein secure bond.Olmesartan is difficult to the blood brain barrier by rat, even can not pass through blood brain barrier.Olmesartan can enter tire by the rat placental barrier.The Olmesartan of small part can be distributed into the milk of rat.
Special population
The child: patient's the pharmacokinetic data available that is lower than 18 years old is not bright.
The old people: in the pharmacokinetic studies of the old people above 65 years old, the maximum plasma concentration of Olmesartan is similar to the adolescent.Observe the phenomenon of accumulating of moderate behind the multiple dosing.CLR descends 30% approximately, and AUCss rises 33% approximately.
Sex: only have small difference.Women's AUC and Cmax all high approximately 10～15%.
The renal insufficiency patient: renal insufficiency patient's serum Olmesartan concentration is than the intact person's height of renal function.AUC rises to 3 multiples approximately behind the severe renal function sufferer multiple dosing.The patient who need is carried out the kidney dialysis does not carry out medication research.
Hepatic insufficiency patient: moderate hepatic insufficiency patient's AUC0-∞ and Cmax exceed 60% approximately than the coupling matched group.
Clinical experiment
Is that the dosage of olmesartan medoxomil is 2.5～80mg, 6～12 weeks of administration cycle in the antihypertensive clinical experiment of contrast at 7 with the placebo; The effect of peak value and valley all occurs significantly bringing high blood pressure down.Among the typical hypertensive patient of 2693 examples (administration group 2145 examples, placebo group 548 examples), olmesartan medoxomil administration once a day can reduce systolic pressure and diastolic pressure, effect and dosage positive correlation (as shown in the figure) altogether.
Every day, 20 milligrams olmesartan medoxomil caused blood pressure valley decline 10/6mmHg.Every day, 40 milligrams olmesartan medoxomil caused blood pressure valley decline 12/7mmHg.The medicine that is higher than 40 milligrams there is no stronger effect.Antihypertensive function occurred in one week of administration, and is obvious after 2 weeks.
The effect that brings high blood pressure down was all arranged in 24 hours after the olmesartan medoxomil administration once a day, the valley/peak value ratio of contraction, diastole effect is between 60～80%.No matter with the hydrochlorothiazide coupling, the effect that brings high blood pressure down of olmesartan medoxomil can be maintained until 1 year.Long-term prescription does not have drug resistance to be taken place, and withdrawal does not have bounce-back after the term medication.
It is similar that age is lower than the pressure reduction effect that men and women's sexually transmitted disease (STD) people of 65 years old uses behind the olmesartan medoxomil.The group difference response class that is occurred with ACE inhibitor, angiotensin receptor blocker and beta receptor blocker seemingly, olmesartan medoxomil is on the weak side to Black people's effect.When being additional to hydrochlorothiazide, olmesartan medoxomil has extra antihypertensive effect.
Untoward reaction
In the quilt 3825 routine hypertensive patients (3275 examples are patients that experiment was selected in of tool matched group) that estimate, the olmesartan medoxomil medication surpasses 900 examples that have in June, and medication surpasses 525 examples in 1 year.Olmesartan medoxomil is by well tolerable, and incidence rate of adverse reaction is similar to placebo.
The untoward reaction gentleness, of short duration, uncorrelated with the olmesartan medoxomil administration, total incidence rate is uncorrelated with dosage.
The ratio that withdraws from test because of adverse events is 2.4%, 2.7% (Olmesartan group vs. matched group); In the test of placebo, the ratio that withdraws from test because of adverse events is 3%, 1% (Olmesartan group vs. matched group);
Above-mentioned digital proof, the olmesartan medoxomil sheet of present embodiment is safely and effectively.
The above is the preferred embodiments of the present invention only, is not limited to the present invention, and for a person skilled in the art, the present invention can have various changes and variation.Within the spirit and principles in the present invention all, any modification of being done, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. olmesartan medoxomil sheet, it is characterized in that the label of 1000 olmesartan medoxomil sheets comprises: olmesartan medoxomil 20g, lactose 1. 60g to 95g, lactose 2. 30g, microcrystalline Cellulose 45g to 50g, 5g PVPK30, low-substituted hydroxypropyl cellulose L-HPC8g, magnesium stearate 1g and be used to make the ethanol water of soft material.
2. olmesartan medoxomil sheet according to claim 1 is characterized in that, the coating solution of described 1000 olmesartan medoxomil sheets comprises: coating powder 5.1g and 64ml ethanol water.
3. olmesartan medoxomil sheet according to claim 1 and 2 is characterized in that, described ethanol water is 50% ethanol water.
4. olmesartan medoxomil sheet according to claim 1 is characterized in that, 1. described lactose is 60g.
5. olmesartan medoxomil sheet according to claim 1 is characterized in that, described microcrystalline Cellulose is 45g.
6. according to the preparation method of each described olmesartan medoxomil sheet in the claim 1 to 5, it is characterized in that, comprising:
Lactose 2., microcrystalline Cellulose, PVPK30 and L-HPC all cross 80 mesh sieves, with olmesartan medoxomil and lactose 1. mixed grinding cross 100,120 or 160 mesh sieves after 2 hours, by recipe quantity will contain olmesartan medoxomil powder and lactose 2., behind the microcrystalline Cellulose, PVPK30, L-HPC mix homogeneously, with ethanol water system soft material, granulate oven dry with 24 mesh sieves, behind the 22 mesh sieve granulate, after adding the magnesium stearate mixing of recipe quantity, stamping is put into the coating pan coating with the gained sheet.
7. preparation method according to claim 6 is characterized in that, olmesartan medoxomil and lactose 1. mixed grinding are crossed 120 mesh sieves after 2 hours.
8. preparation method according to claim 6 is characterized in that, uses 50 ℃ of oven dry.
9. preparation method according to claim 6 is characterized in that, with φ 8mm stamping.
10. preparation method according to claim 6 is characterized in that, the gained sheet is put into coating pan coating weightening finish 2-3%.
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|---|---|---|---|
| CN 201010224565 CN102119930B (en) | 2010-07-13 | 2010-07-13 | Olmesartan medoxomil tablets and preparation method thereof |
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| CN102119930A true CN102119930A (en) | 2011-07-13 |
| CN102119930B CN102119930B (en) | 2013-01-30 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104398485A (en) * | 2014-12-10 | 2015-03-11 | 哈药集团技术中心 | Olmesartan medoxomil tablet and preparation method thereof |
| CN105640913A (en) * | 2016-01-22 | 2016-06-08 | 山东省医学科学院药物研究所 | Olmesartan medoxomil tablet and preparation method thereof |
| CN110638772A (en) * | 2019-10-29 | 2020-01-03 | 白喜平 | Olmesartan medoxomil tablet and preparation method thereof |
| CN111557924A (en) * | 2020-05-13 | 2020-08-21 | 重庆赛凌医药有限公司 | Preparation method of olmesartan medoxomil hydrochlorothiazide tablet and olmesartan medoxomil hydrochlorothiazide tablet |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101066264A (en) * | 2007-06-12 | 2007-11-07 | 杨喜鸿 | Solid olmesartan medoxmil dispersion and its prepn and medicinal application |
| CN101478966A (en) * | 2006-06-27 | 2009-07-08 | 第一三共株式会社 | Compressed preparation |
-
2010
- 2010-07-13 CN CN 201010224565 patent/CN102119930B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101478966A (en) * | 2006-06-27 | 2009-07-08 | 第一三共株式会社 | Compressed preparation |
| CN101066264A (en) * | 2007-06-12 | 2007-11-07 | 杨喜鸿 | Solid olmesartan medoxmil dispersion and its prepn and medicinal application |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104398485A (en) * | 2014-12-10 | 2015-03-11 | 哈药集团技术中心 | Olmesartan medoxomil tablet and preparation method thereof |
| CN104398485B (en) * | 2014-12-10 | 2017-05-10 | 哈药集团技术中心 | Olmesartan medoxomil tablet and preparation method thereof |
| CN105640913A (en) * | 2016-01-22 | 2016-06-08 | 山东省医学科学院药物研究所 | Olmesartan medoxomil tablet and preparation method thereof |
| CN105640913B (en) * | 2016-01-22 | 2018-11-02 | 山东省医学科学院药物研究所 | A kind of olmesartan medoxomil tablet and preparation method thereof |
| CN110638772A (en) * | 2019-10-29 | 2020-01-03 | 白喜平 | Olmesartan medoxomil tablet and preparation method thereof |
| CN111557924A (en) * | 2020-05-13 | 2020-08-21 | 重庆赛凌医药有限公司 | Preparation method of olmesartan medoxomil hydrochlorothiazide tablet and olmesartan medoxomil hydrochlorothiazide tablet |
| CN111557924B (en) * | 2020-05-13 | 2022-05-10 | 重庆赛凌医药有限公司 | Preparation method of olmesartan medoxomil hydrochlorothiazide tablet and olmesartan medoxomil hydrochlorothiazide tablet |
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| CN102119930B (en) | 2013-01-30 |
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