CN1698618A - Double layer tablet of artesunate and hydrochloric amodiaquine and preparation method thereof - Google Patents
Double layer tablet of artesunate and hydrochloric amodiaquine and preparation method thereof Download PDFInfo
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- CN1698618A CN1698618A CN 200510026511 CN200510026511A CN1698618A CN 1698618 A CN1698618 A CN 1698618A CN 200510026511 CN200510026511 CN 200510026511 CN 200510026511 A CN200510026511 A CN 200510026511A CN 1698618 A CN1698618 A CN 1698618A
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Abstract
The invention discloses a double layer tablet of artesunate and hydrochloric amodiaquine and preparation process, which comprises active composition, auxiliary material and solubilizing agent, the formulation is also charged by disintegrating agent selected from propyl hydroxypropylcellulose, crystalline cellulose and sodium carboxymethylstarch. The dissolving rate of the product can reach over 85%.
Description
Technical field
The present invention relates to the compound preparation of a kind of artesunate and Camoquin, relate in particular to the double-layer tablet of a kind of artesunate and Camoquin.
Background technology
Malaria is one of the most common disease in the torrid zone, subtropical zone.In many third world countries, the M ﹠ M of malaria is still high.Malaria still is distributed in more than 100 countries and regions, the whole world at present.WHO in 1998 estimates that the whole world has 3～500,000,000 people to catch malaria every year, because of these about 3,000,000 people that die that die of illness, 90% dead patient occurs in Africa, wherein surpasses 90% Africa child below 5 years old, malaria is murdered 3000 children every day, murders 1,000,000 children in 1 year in Africa.1999-2002 is subjected to malaria to threaten the population change situation to show in different prevalence rates area: changes the fastest, growth is maximum is African area and south east asia.The regional compromised population in Africa rises to 600,000,000 5 thousand ten thousand in 20th century from 6,000,000, lives in the high popular district of malaria and the district of being very popular more than 80%.
Although African malaria wildness, because of economy is backward relatively, the cheap chloroquine of the long-term a large amount of uses of people is treated as a line medicine.Because of excessive life-time service chloroquine, malaria has produced drug resistance to chloroquine and derivant thereof in more than 80 country in the whole world, and most of regional chloroquine is invalid to plasmodium in Southeast Asia and Africa
[2]It is dead closely related to the increase of chloroquine drug resistance with plasmodium that a large amount of children in Africa suffer from malaria.
Consider under the prerequisite of African ability to shoulder economically, in order to suppress African malaria epidemic situation, reduce African plasmodial drug resistance, WHO proposes the scheme of reform traditional treatment malaria, recommends to adopt the drug combination based on artemisinin-based drug, is called for short the ACT therapy.The ACT therapeutic scheme that WHO recommends comprises: amodiaquine/artesunate, Artemether/LUMEFANTRINE (Coartem), SP (sulfadoxine/pyrimethamine)/artesunate, mefloquine/artesunate.The ACT treatment has been selected by existing 40 countries in the whole world at present: 36 countries are as the first-line treatment medicine, and 4 countries are as the two wires medicine, and country is just considering to change into the ACT therapy recently more than 14.
Artesunate mainly acts on the wireless body of plasmodium erythrocytic stage, and model of action mainly is to disturb pellicle one mitochondrial function.It has following effect characteristics: (1) is effective to anti-chloroquine pernicious malaria; (2) can kill plasmodium erythrocytic stage phorozoon fast, control malaria symptom; (3) compare with other antimalarial, the effect of paying of this product is little.This product half-life of its shortcoming is short, the treatment short course of treatment (3 days), and parasite killing is not thorough, protozoon recrudescence rate height, need extend the period of treatment (6～7 days) could thoroughly be killed plasmodium and improve cure rate.Compare with other antimalarial, its price comparison is expensive.
The amodiaquine structure is similar to chloroquine with effect, can effectively kill various plasmodium phorozoons in the erythrocytic stage, and the ripe gametocyte of tertian malaria, quartan malaria and ovale malaria is also had certain effect, but then invalid to the infrared phase plasmodium of the paulospore in the hepatocyte.It has following effect characteristics: (1) is effective to anti-chloroquine pernicious malaria; (2) various plasmodial phorozoons in the blood all there is stronger killing action, can controls clinical symptoms rapidly, the ripe gametocyte and the immature Plasmodium falciparum gametocyte of tertian malaria, quartan malaria and ovale malaria also had killing action; (3) cheap.This product toxicity of its shortcoming is bigger than other antimalarial.Because amodiaquine is cheap, determined curative effect and toleration are good when being used for the treatment of malaria, thus in African area will its as a line malaria medicine for treatment.
The conventional medicament based on artesunate that WHO proposes is united use, is to tackle the chemical sproof effective way of pernicious malaria.Artesunate can reduce the multi-drug resistant plasmodium rapidly, and the nubbin plasmodium just can be killed by the combination medicine of high concentration (for example amodiaquine), and the medication combined use of different mechanism of action has improved curative effect.Simultaneously, because curative effect of medication is high and the minimizing of gametocyte quantity, can weaken malaria transmission, and plasmodium is also lower to two kinds of all drug-fast probabilities of medicine, the plasmodium drug resistance should be quite slow due to the drug combination.Therefore amodiaquine and artesunate drug combination treatment malaria is very effective.
At present, the packing method of drug combination is that two kinds of different medicines are pressed on the same bubble cap tray in the world, needs when patient takes two kinds of different pharmaceuticals are taken out, and quantitatively takes.This method is obviously very inconvenient, occurs the mistake thing phenomenon of taking medicine easily.How artesunate and amodiaquine are made compound preparation so that the taking of people, be people the problem that solves of expectation very.
Summary of the invention
Technical problem to be solved by this invention is to disclose a kind of artesunate and amodiaquine hydrochloride bilayer tablet and preparation method thereof to overcome the defective that prior art exists.
Artesunate of the present invention and amodiaquine hydrochloride bilayer tablet are by artesunate tablet and the compound formation of Camoquin (base) sheet, artesunate tablet is made up of active ingredient artesunate and adjuvant, and Camoquin (base) sheet is made up of active ingredient Camoquin (base), adjuvant and solubilizing agent; The content of artesunate is 8～11% of tablet total weight amount, and Camoquin (base) content is 24～33% of tablet total weight amount, and preferred part by weight is:
Artesunate: Camoquin (base)=1: 3.
Said adjuvant comprises pharmaceutically acceptable filler and/or binding agent and/or disintegrating agent and/or lubricant etc.;
Said filler is selected from a kind of or its mixture in starch, dextrin, sucrose or the lactose etc., and consumption is 10～60% of a tablet total weight amount;
Said binding agent is selected from polyvinylpyrrolidone, hydroxypropyl emthylcellulose or ethanol etc., and consumption is 1～20% of a tablet total weight amount;
Said disintegrating agent is selected from a kind of or its mixture in microcrystalline Cellulose, carboxymethylstach sodium, hyprolose, cross-linking sodium carboxymethyl cellulose or the cross-linked ethylene ketopyrrolidine etc., and consumption is 1～50% of a tablet total weight amount;
Said lubricant is selected from a kind of or its mixture in magnesium stearate or the Pulvis Talci etc., and consumption is 0.5～2.0% of a tablet total weight amount.
Said solubilizing agent is an anion surfactant or/and non-ionic surface active agent, and preferred polyoxyethylene sorbitan monoleate is or/and sodium lauryl sulphate etc., and consumption is 0.05～3% of a tablet total weight amount.
The disintegrating agent that the present invention adds in prescription is selected from hydroxypropyl cellulose, microcrystalline Cellulose, carboxymethyl starch sodium, and the solubilizing agent that adds, the dissolution that can make this product is up to more than 85%, and (artesunate tablet dissolution standard is: 30 minutes 〉=60% to exceed 15%～30% percentage point than folk prescription tablet dissolution standard; Camoquin sheet dissolution standard is: 30 minutes 〉=75%), improved the bioavailability of this product, improved product quality.Before not adding above-mentioned disintegrating agent and solubilizing agent, the dissolution of product is about 40～50% only, does not meet standard-required.
Hydroxypropyl cellulose, microcrystalline Cellulose are cellulose derivative, the hygroscopicity preferably and the water absorption of tool, this character has increased its swelling capacity greatly, can quicken the disintegrate of tablet and the dispersive fineness after the disintegrate, thereby accelerate the dissolution rate of medicine, improve bioavailability.
Carboxymethyl starch sodium is the potato starch derivant, and it is moist that tool stronger drawn, and water absorbing force is big, can absorb 30 times of its dry bulk.Suction back powder expands and does not dissolve, so do not hinder the continuation infiltration of moisture and influence the further disintegrate of slice, thin piece, is a good disintegrating agent, can accelerate the dissolution rate of medicine, improves bioavailability.
The solubilizing agent that the present invention uses has following characteristics:
Polyoxyethylene sorbitan monoleate is a nonionic surfactant, and sodium lauryl sulphate is an anion surfactant, and tablet is with after gastric juice contacts, this product can reduce its surface tension, increase the wettability of slice, thin piece, make moisture content borrow the capillarity of tablet, rapid permeability causes disintegrate to label.But its independent action effect is not good enough, share with disintegrating agent of the present invention, can play auxiliary disintegrate and use.
Preparation method of the present invention comprises the following steps:
(1) the particulate preparation of artesunate:
Is that 50～90% ethanol water is made binding agent with artesunate, filler, disintegrating agent and lubricant with weight concentration, adopts method well known in the art to granulate, and 50～60 ℃ of dryings are standby;
In this step, the addition of filler is 10～60% of an artesunate granule gross weight;
The addition of lubricant is 0.5～2.0% of an artesunate granule gross weight;
The addition of binding agent is 1～20% of an artesunate granule gross weight;
(2) the particulate preparation of Camoquin (base)
With filler and the lubricant of surplus and the binding agent that contains the surplus of surfactant of Camoquin (base), surplus, be 8% corn starch liquid as weight content, adopt method well known in the art to granulate, 50～60 ℃ of dryings, standby;
In the above-mentioned binding agent, the surfactant weight concentration is 0.05～3%, and binder wt concentration is 5～10%
(3) artesunate adds the preparation of amodiaquine hydrochloride compound preparation (double-layer tablet):
Artesunate granule and Camoquin granule are adopted the tablet machine tabletting, promptly obtain artesunate and add amodiaquine hydrochloride bilayer tablet.
Said tablet machine is a kind of common apparatus, is the tablet machine of ZP-21W as model.
Get its finished product and carry out content and dissolution test, the artesunate weight content is 98.2%～99.8%, and dissolution can reach 85%～97.5% in 30 minutes; The Camoquin weight content is 97.2%～99.8%, and dissolution can reach 85%～92.5% in 30 minutes.
In the finished product content and determination of dissolution rate respectively by " in the Chinese Pharmacopoeia version in 2000 in artesunate tablet standard and " American Pharmacopeia " 27 editions Camoquin sheet standard measure.
Artesunate of the present invention adds amodiaquine hydrochloride bilayer tablet and can be used for treating pernicious malaria, and dosage is generally artesunate 1～4mg/kg, and amodiaquine 10mg～12mg/kg body weight specifically can be determined by the doctor according to patient's age, sex and the state of an illness.Can put on the patient who needs treatment by oral mode.
Because the present invention has added surfactant and cooperated with this surfactant in tablet disintegrating agent, therefore, dissolution improves greatly, can obviously reduce taking dose and improve therapeutic effect, taking convenience, medication can not lead to errors, especially for child and old man, more convenient.
The specific embodiment
Embodiment 1
1. the artesunate granule is write out a prescription:
Artesunate 50mg
Corn starch 40%
Sucrose 10%
Hydroxypropyl cellulose 10%
Microcrystalline Cellulose 20%
Magnesium stearate 0.8%
More than being weight concentration, is benchmark with particulate weight, down together.
2. the Camoquin granule is write out a prescription:
Camoquin (base) 150mg
Corn starch 9%
Dextrin 8%
Hydroxypropyl cellulose 2%
Microcrystalline Cellulose 7%
Polyoxyethylene sorbitan monoleate 0.05%
Magnesium stearate 1%
3. preparation method:
The artesunate preparation of granules:
Artesunate is pressed the weighing of prescription consumption, put the interior pulverizing of flour mill and cross 60 mesh sieves, corn starch, sucrose, hydroxypropyl cellulose, microcrystalline Cellulose and magnesium stearate are respectively by the weighing of prescription consumption, cross 60 mesh sieves, active ingredient and adjuvant are mixed in the rearmounted granulator, make binding agent, granulate with 75% alcoholic solution, in 55 ℃ of dryings, 16 mesh sieve granulate;
The Camoquin preparation of granules:
Sour amodiaquine is pressed the weighing of prescription consumption, put the interior pulverizing of flour mill and cross 60 mesh sieves, Camoquin, dextrin, hydroxypropyl cellulose, microcrystalline Cellulose and magnesium stearate are added the corn starch liquid that contains polyoxyethylene sorbitan monoleate make binding agent, granulate, in 60 ℃ of dryings, 16 mesh sieve granulate;
Artesunate adds the preparation of amodiaquine hydrochloride compound preparation (double-layer tablet):
It is tabletting in the tablet machine of ZP-21W that artesunate granule and Camoquin granule are placed model, can make artesunate and add amodiaquine hydrochloride bilayer tablet.
Adopt the method for this company standard regulation to carry out the finished product chemical examination, the result:
Artesunate content: 98.8%, dissolution: 45.6%; Camoquin content: 97.9%, dissolution: 52.8%
Embodiment 2
1. the artesunate granule is write out a prescription
Supplementary material title consumption (mg)
Artesunate 50mg
Corn starch 38%
Sucrose 10%
Hydroxypropyl cellulose 10%
Microcrystalline Cellulose 20%
Carboxymethyl starch sodium 2%
Magnesium stearate 0.8%
2. the Camoquin granule is write out a prescription
Camoquin (base) 150mg
Corn starch 9%
Dextrin 6%
Hydroxypropyl cellulose 2%
Microcrystalline Cellulose 6%
Carboxymethyl starch sodium 2%
Sodium lauryl sulphate 1%
Magnesium stearate 1%
Preparation method is with embodiment 1.
Finished product result of laboratory test: artesunate content: 98.8%, dissolution: 78.6%; Camoquin content: 97.9%, dissolution: 72.8%.
Embodiment 3
1. the artesunate granule is write out a prescription:
Artesunate 50mg
Corn starch 29%
Sucrose 8%
Hydroxypropyl cellulose 15%
Microcrystalline Cellulose 25%
Carboxymethyl starch sodium 3%
Magnesium stearate 0.8%
2. the Camoquin granule is write out a prescription:
Camoquin (base) 150mg
Corn starch 9%
Dextrin 5%
Hydroxypropyl cellulose 3%
Microcrystalline Cellulose 6%
Carboxymethyl starch sodium 3%
Polyoxyethylene sorbitan monoleate 0.1%
Magnesium stearate 1%
Preparation method is with embodiment 1.
Finished product result of laboratory test: artesunate content: 98.8%, dissolution: 82.4%; Camoquin content: 97.9%, dissolution: 75.9%
Embodiment 4
1. the artesunate granule is write out a prescription:
Artesunate 50mg
Corn starch 23%
Sucrose 8%
Hydroxypropyl cellulose 20%
Microcrystalline Cellulose 25%
Carboxymethyl starch sodium 4%
Magnesium stearate 0.8%
2. the Camoquin granule is write out a prescription:
Camoquin (base) 150mg
Corn starch 9%
Dextrin 4%
Hydroxypropyl cellulose 4%
Microcrystalline Cellulose 5%
Carboxymethyl starch sodium 3.5%
Polyoxyethylene sorbitan monoleate 1%
Magnesium stearate 1%
Preparation method is with embodiment 1.
Finished product result of laboratory test: artesunate content: 98.8%, dissolution: 90.2%; Camoquin content: 97.9%, dissolution: 87.6%
Embodiment 5
1. the artesunate granule is write out a prescription:
Artesunate 50mg
Corn starch 17.8%
Sucrose 8%
Hydroxypropyl cellulose 25%
Microcrystalline Cellulose 25%
Carboxymethyl starch sodium 4%
Magnesium stearate 1.0%
Camoquin granule prescription
Camoquin (base) 150mg
Corn starch 9%
Dextrin 3%
Hydroxypropyl cellulose 4%
Microcrystalline Cellulose 5%
Carboxymethyl starch sodium 4%
Polyoxyethylene sorbitan monoleate 1.5%
Magnesium stearate 1.0%
Preparation method is with embodiment 1.
Finished product result of laboratory test: artesunate content: 98.8%, dissolution: 95.2%; Camoquin content: 97.9%, dissolution: 92.3%
Embodiment 6
Artesunate granule prescription
Artesunate 50mg
Corn starch 10.8%
Sucrose 5%
Hydroxypropyl cellulose 30%
Microcrystalline Cellulose 30%
Carboxymethyl starch sodium 4%
Magnesium stearate 1.0%
Camoquin granule prescription
Camoquin (base) 150mg
Corn starch 9%
Dextrin 3%
Hydroxypropyl cellulose 4%
Microcrystalline Cellulose 4%
Carboxymethyl starch sodium 4%
Polyoxyethylene sorbitan monoleate 2.5%
Magnesium stearate 1.0%
Preparation method is with embodiment 1.
Finished product result of laboratory test: artesunate content: 98.8%, dissolution: 93.8%; Camoquin content: 97.9%, dissolution: 92.3%.
Embodiment 7
Adopt the tablet of embodiment 1 to test, carry out artesunate granule and Camoquin preparation of granules by embodiment 1 method.Getting prepared artesunate granule and Camoquin granule is ZP-21W tablet machine tabletting in model.Its finished product is detected, and artesunate content is 99.3%, and dissolution is 47.5%; Camoquin content is 98.9%, and dissolution is 41.5%.
Artesunate adds the malaria pharmacodynamics test of amodiaquine hydrochloride bilayer tablet:
One. artesunate adds the effect of amodiaquine hydrochloride bilayer tablet to Mus plasmodium erythrocytic stage
1 pair of normal strain of Mus plasmodium
Method: adopt the normal strain model of Mus plasmodium (Plasmodium berghei).Get healthy mice male and female one and arrest, body weight 18～22 grams, random packet, 20 every group Mus malaria kind Mus are got blood to pull out a method.Anticoagulant heparin, the normal saline dilution.Every 0.1ml hemodilution liquid contains about 5,000 ten thousand of plasmodiums.And the abdominal cavity inoculation, inoculate back 24 hours and begin to observe, from the mice fever, add amodiaquine hydrochloride bilayer tablet, continuous 3 days for respectively the artesunate of artesunate tablet, Camoquin sheet and the embodiment 5 of various dose.During the medication, measure mouse temperature, drug withdrawal afterbody next day is got blood and is coated with paper tinsel, thick blood film sheet, observes the plasmodium situation of turning out cloudy, and the results are shown in Table 1.
Table 1
Artesunate tablet, Camoquin sheet and artesunate add the effect of amodiaquine hydrochloride bilayer tablet to the normal strain erythrocytic stage of Mus plasmodium
| Medicine | Dosage (mg/kg time) | Route of administration | The protozoon clearance time (hour) | First day fever clearance rate (%) |
| Artesunate tablet | ?????80 | Irritate stomach | ???????60 | ???????90 |
| Artesunate tablet | ?????120 | Irritate stomach | ???????48 | ???????96 |
| The Camoquin sheet | Base: 150 | Irritate stomach | ???????48 | ???????84 |
| Artesunate adds amodiaquine hydrochloride bilayer tablet | Artesunate: 50 amodiaquines: 150 | Irritate stomach | ???36 | ???97 |
| Matched group | It is 35% that next day is counted the protozoan infection rate in drug withdrawal | |||
The result: heavy dose of as seen from Table 1 artesunate tablet is identical with Camoquin sheet protozoon clearance time, but first day fever clearance rate is higher; Low dose of artesunate tablet protozoon clearance time is longer, and first day fever clearance rate is low than heavy dose of artesunate tablet.But low dose of artesunate and make the double-layer tablet medication with the dosage Camoquin after, its speed of turning out cloudy is faster with artesunate tablet and Camoquin sheet than single, the fever clearance rate was identical with the artesunate tablet of heavy dose in first day.The above results shows artesunate and Camoquin drug combination, and artesunate can increase the malaria effect of Camoquin.
2 pairs of anti-chloroquine strains of Mus plasmodium
Method: the same substantially, but adopt the anti-chloroquine strain of Mus plasmodium model to observe, medicine then increases chloroquine, the results are shown in Table 2.
Table 2
Artesunate adds the effect of amodiaquine hydrochloride bilayer tablet to the anti-chloroquine strain of Mus plasmodium erythrocytic stage
| Medicine | Dosage (mg/kg time) | Route of administration | The protozoon clearance time (hour) | First day fever clearance rate (%) |
| Artesunate tablet | ??????80 | Irritate stomach | ???????60 | ??????90 |
| Artesunate tablet | ??????120 | Irritate stomach | ???????48 | ??????96 |
| The Camoquin sheet | Base: 150 | Irritate stomach | ???????48 | ??????84 |
| Artesunate adds amodiaquine hydrochloride bilayer tablet | Artesunate: 50 amodiaquines: 150 | Irritate stomach | ???????36 | ??????97 |
| Chloroquine | ???????80 | Irritate stomach | ||
| Matched group | It is 36% that next day is counted the protozoan infection rate in drug withdrawal | |||
The result: as seen from Table 2, artesunate adds amodiaquine hydrochloride bilayer tablet antagonism chloroquine strain protozoon erythrocytic stage killing action.And chloroquine does not have effect, also shows that this product and chloroquine do not have cross resistance.
Two. artesunate adds amodiaquine hydrochloride bilayer tablet toxicity
Add the anxious poison reaction that amodiaquine hydrochloride bilayer tablet has been observed animal after to mouse stomach with artesunate, and measure LD
50Value and 95% fiducial limit thereof, the result is as follows: the mouse stomach artesunate adds the amodiaquine double-layer tablet, and dosage is 750,600,450,300,150mg/kg (amodiaquine), and poisoning symptom is dead for twitching.Calculate mice (PO) LD with the Bliss method
50Value is for 560.28mg/kg, with the 95% credible 480.08～640.48mg/kg that is limited to.The oral LD of bibliographical information artesunate toxicity
50Be 1002.57mg/kg, the oral LD of amodiaquine toxicity toxicity
50Be 550.00mg/kg, illustrate that artesunate toxicity is littler than amodiaquine toxicity, make the compound recipe sheet and use, toxicity is not seen increase, and toxicity is similar to the amodiaquine folk prescription.As seen to use within the specific limits be safe to the compound recipe sheet.
Three. artesunate adds the amodiaquine hydrochloride bilayer tablet pharmacokinetics
The artesunate of selecting for use embodiment 5 to make adds amodiaquine hydrochloride bilayer tablet.Select 15 of 1.5～2.0kg/ rabbit only for use, be divided into 3 groups, 4 of every group of male rabbits, 1 of doe, oral (PO) contains the compound recipe sheet of artesunate 25mg/kg, amodiaquine 75mg/kg; The alternative body weight is 5 of 14～20kg/ dog only, oral (PO) contains the compound recipe sheet of artesunate 15mg/kg, amodiaquine 45mg/kg, different time is got blood by vein after the administration, separation of serum, place-30 ℃ to preserve survey fully, artesunate adopts measured by radioimmunoassay, and amodiaquine adopts high effective liquid chromatography for measuring, the results are shown in Table 3.
Table 3 rabbit and Canis familiaris L. oral administered compound artesunate add the pharmacokinetic parameter of amodiaquine sheet
| Animal | Rabbit | Canis familiaris L. | ||
| Dosage (mg/kg) | Artesunate | Amodiaquine | Artesunate | Amodiaquine |
| ????Art：25 | ????Amod：75 | ????Art：15 | ???Amod：45 | |
| Peak time (h) | ????0.75±0.20 | ????1.1±0.38 | ????0.85±0.21 | ???1.05±0.42 |
| Peak concentration (ug/ml) | ????1.8±0.45 | ????0.04±0.02 | ????1.9±0.5 | ???0.04±0.02 |
| ???AUC(ugih/ml) | ????1.1±0.52 | ????0.32±0.09 | ????1.2±0.4 | ???0.32±0.08 |
| ????T 1/2(h) | ??0.7±0.45 | ??13.5±4.9 | ??0.68±0.45 | ??14.9±4.5 |
As can be known from Table 3, oral artesunate and the amodiaquine compound recipe sheet of containing of rabbit and Canis familiaris L., artesunate, amodiaquine all can absorb well, and peak time is rapid, artesunate blood level height, metabolism is fast, and the amodiaquine blood level is low, and metabolism is slow.
Claims (10)
1. artesunate and amodiaquine hydrochloride bilayer tablet, it is characterized in that, by artesunate tablet and the compound formation of Camoquin (base) sheet, artesunate tablet is made up of active ingredient artesunate and adjuvant, and Camoquin (base) sheet is made up of active ingredient Camoquin (base), adjuvant and solubilizing agent;
Said adjuvant comprises pharmaceutically acceptable filler and/or binding agent and/or disintegrating agent and/or lubricant;
Said disintegrating agent is selected from a kind of or its mixture in microcrystalline Cellulose, carboxymethylstach sodium, hyprolose, cross-linking sodium carboxymethyl cellulose or the cross-linked ethylene ketopyrrolidine, and consumption is 1～50% of a tablet total weight amount;
Said solubilizing agent is an anion surfactant or/and non-ionic surface active agent, and preferred polyoxyethylene sorbitan monoleate is or/and sodium lauryl sulphate etc., and consumption is 0.05～2% of a tablet total weight amount.
2. artesunate according to claim 1 and amodiaquine hydrochloride bilayer tablet is characterized in that, the content of active ingredient artesunate is 8～11% of tablet total weight amount, and Camoquin (base) content is 24～33% of tablet total weight amount.
3. artesunate according to claim 1 and amodiaquine hydrochloride bilayer tablet is characterized in that, part by weight is: artesunate: Camoquin (base)=1: 3.
4. artesunate according to claim 1 and amodiaquine hydrochloride bilayer tablet is characterized in that, said filler is selected from a kind of or its mixture in starch, dextrin, sucrose or the lactose, and consumption is 10～60% of a tablet total weight amount.
5. artesunate according to claim 4 and amodiaquine hydrochloride bilayer tablet is characterized in that, said filler loading is 10～60% of a tablet total weight amount.
6. artesunate according to claim 1 and amodiaquine hydrochloride bilayer tablet is characterized in that said binding agent is selected from polyvinylpyrrolidone, hydroxypropyl emthylcellulose or ethanol.
7. artesunate according to claim 6 and amodiaquine hydrochloride bilayer tablet is characterized in that, binder dosage is 1～20% of a tablet total weight amount.
8. artesunate according to claim 1 and amodiaquine hydrochloride bilayer tablet is characterized in that said lubricant is selected from a kind of or its mixture in magnesium stearate or the Pulvis Talci etc., and consumption is 0.5～2.0% of a tablet total weight amount.
9. according to claim 1～8 each described artesunate and amodiaquine hydrochloride bilayer tablet, it is characterized in that solubilizing agent is that polyoxyethylene sorbitan monoleate is or/and sodium lauryl sulphate.
10. according to the preparation method of each described artesunate of claim 1～9 and amodiaquine hydrochloride bilayer tablet, it is characterized in that, comprise the following steps:
(1) the particulate preparation of artesunate:
Is that 50～90% ethanol water is made binding agent with artesunate, filler, disintegrating agent and lubricant with weight concentration, adopts method well known in the art to granulate, and 50～60 ℃ of dryings are standby;
In this step, the addition of filler is 10～60% of an artesunate granule gross weight;
The addition of lubricant is 0.5～2.0% of an artesunate granule gross weight;
The addition of binding agent is 1～20% of an artesunate granule gross weight;
(2) the particulate preparation of Camoquin (base)
With filler and the lubricant of surplus and the remainder binder that contains surfactant of Camoquin (base), surplus, adopt method well known in the art to granulate, 50～60 ℃ of dryings, standby;
In the above-mentioned binding agent, the surfactant weight concentration is 0.05～3%, and binder wt concentration is 5～10%
(3) artesunate adds the preparation of amodiaquine hydrochloride compound preparation (double-layer tablet):
Artesunate granule and Camoquin granule are adopted the tablet machine tabletting, promptly obtain artesunate and add amodiaquine hydrochloride bilayer tablet.
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| CN 200510026511 CN1698618A (en) | 2005-06-07 | 2005-06-07 | Double layer tablet of artesunate and hydrochloric amodiaquine and preparation method thereof |
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| CN 200510026511 CN1698618A (en) | 2005-06-07 | 2005-06-07 | Double layer tablet of artesunate and hydrochloric amodiaquine and preparation method thereof |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200510026511 Pending CN1698618A (en) | 2005-06-07 | 2005-06-07 | Double layer tablet of artesunate and hydrochloric amodiaquine and preparation method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN1698618A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007043061A1 (en) * | 2005-10-11 | 2007-04-19 | Ipca Laboratories Ltd. | Anti-malarial combination and methods of formulation |
| WO2011032318A1 (en) * | 2009-09-21 | 2011-03-24 | 上海复星普适医药科技有限公司 | Stable artesunate-amodiaquine hydrochloride complex tablet and preparation method thereof |
| CN101756982B (en) * | 2008-12-17 | 2012-07-04 | 重庆医药工业研究院有限责任公司 | Artesunate compound medicine composition with improved mouth feeling and high stability |
-
2005
- 2005-06-07 CN CN 200510026511 patent/CN1698618A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007043061A1 (en) * | 2005-10-11 | 2007-04-19 | Ipca Laboratories Ltd. | Anti-malarial combination and methods of formulation |
| CN101756982B (en) * | 2008-12-17 | 2012-07-04 | 重庆医药工业研究院有限责任公司 | Artesunate compound medicine composition with improved mouth feeling and high stability |
| WO2011032318A1 (en) * | 2009-09-21 | 2011-03-24 | 上海复星普适医药科技有限公司 | Stable artesunate-amodiaquine hydrochloride complex tablet and preparation method thereof |
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