CN102038677A - Brominated dihydroartemisinin compound double-releasing preparation - Google Patents
Brominated dihydroartemisinin compound double-releasing preparation Download PDFInfo
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- CN102038677A CN102038677A CN2009101678942A CN200910167894A CN102038677A CN 102038677 A CN102038677 A CN 102038677A CN 2009101678942 A CN2009101678942 A CN 2009101678942A CN 200910167894 A CN200910167894 A CN 200910167894A CN 102038677 A CN102038677 A CN 102038677A
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- bromodihydroartemisiand
- ferrous sulfate
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Abstract
The invention discloses a novel brominated dihydroartemisinin compound double-releasing preparation and preparing components thereof. The preparation is maximally characterized by comprising the steps: preparing a compound preparation from the brominated dihydroartemisinin and the ferrous sulfate, dissolving and fast releasing a ferrous sulfate micro ball in the stomach in the same preparation, and dissolving and fast releasing a brominated dihydroartemisinin micro ball in the intestine, thereby solving the problem that the brominated dihydroartemisinin and the compounded agent ferrous sulfate can be taken simultaneously but can be dissolved in the stomach simultaneously. The technology of the novel brominated dihydroartemisinin compound double-releasing preparation is simple, is easy to operate, is suitable for the industrialized production, and leads a product to be higher in quality stability, better in anticancer effect, and lower in side effect.
Description
Technical field
The invention belongs to pharmaceutical field, relate to and a kind ofly Bromodihydroartemisiand is made enteric sustained-release pellet and ferrous sulfate make the same capsular two preparation technologies that release compound preparation that pack into behind the gastric solubleness fast release micropill.Preparation of the present invention is mainly used in treatment broad-spectrum cancer.
Background technology
I have invented synthetic Bromodihydroartemisiand derivant, its parent nucleus---arteannuin according to recently extensively report has antitumaous effect, what we were early stage studies show that: Bromodihydroartemisiand has than parent nucleus antitumaous effect more efficiently.The mechanism of action is because cancer cell when division needs a large amount of ironys could repetition DNAs, so the irony content of cancerous cell is more high than normal cell.The interior oxo bridge structure that has a uniqueness in the arteannuin molecule, with after ferrum contacts in the oxo bridge fracture produce the charge atom that is called " free radical ".Free radical is launched a offensive to cell membrane, causes the bloated of cancerous cell to die or apoptosis.Because ferrum and the inseparability of oxo bridge group on anti-cancer function simultaneously also for patient's taking convenience, are preferably made compound preparation with chalybeate and Bromodihydroartemisiand.But chalybeate and Bromodihydroartemisiand are directly met the injury that causes easily parietal cell in the stomach the inside.Is under the gastric acid condition, absorbs according to chalybeate, and Bromodihydroartemisiand is the characteristics that begin to absorb at jejunum that with the enteric coated pill of Bromodihydroartemisiand, chalybeate is common gastric solubleness micropill in the stomach the inside.Bromodihydroartemisiand is that slow release, chalybeate are rapid release, in time with on the tissue site two kinds of compositions separately just can be avoided the side effect that injures one's stomach.
Making two micropills of releasing dresses up capsule and mainly contains following advantage: 1. can by the micropill coating or not coating make rapid release or slow releasing preparation; 2. big at the gastrointestinal tract distribution area, the bioavailability height, zest is little; 3. because particle diameter is little, be subjected to digestive tract to carry the food rhythm and pace of moving things to influence little; 4. two micropills of releasing can make different fine horses branches realize by clinical requirement; 5. the good fluidity of micropill is evenly big or small, is easy to preparation; 6. the compatibility that is fit to compound preparation.
Summary of the invention
The two pellet preparations of releasing of the compound recipe that emphasis of the present invention is made up of Bromodihydroartemisiand and ferrous sulfate, slow-release micro-pill are that Bromodihydroartemisiand and pharmaceutically acceptable excipient make earlier that the ball core is then enteric coated again to form; Ferrous sulfate is then made the gastric solubleness fast release micropill with pharmaceutically acceptable excipient, then slow-release micro-pill and fast release micropill is loaded on to make in the common gastric-dissolved capsule shell by the dosage of clinical requirement and twoly releases capsule, is two compound preparations of releasing micropill.
The invention provides Bromodihydroartemisiand slow-release micro-pill and coated formula, described prescription contains: Bromodihydroartemisiand 1.0-20.g, preferred 4.0-8.0g makes the ball core with lactose, starch, magnesium stearate or various modified starch and acceptable one or more total amounts of other excipient of pharmaceutical field 1-30g, preferred 5-15g; Its sustained release coating material is enteric acrylic acid 3-8g, ethylene diester 0.1-1.5g, tween 80 0.1-1.5g, Oleum Ricini 2-4ml, 80-95% ethanol 100ml; After enteric acrylic acid is dissolved in 80% ethanol, add all the other compositions, carry out coating behind the mixing fully.Every capsule contains the bromo dihydroarteannuin and should be 0.02g to 0.08g, choosing grain 30 orders.The coating material slow-release time of this prescription is 2-3 hour, and dissolving PH is 5.3-6.5, and irrelevant with the clothing bed thickness, meet can not in gastric acid, dissolve and will be in intestinal dissolved clinical requirement.The enteric coating material that uses commercially available complete water type also is one of the most practical method in the present invention as the coating of slow-release micro-pill.
The present invention also provides the ferrous sulfate fast release micropill, described micropill contains: ferrous sulfate 0.5-10.g, preferred 1.0-3.0g, acceptable one or more total amounts of other excipient of lactose, dextrin and pharmaceutical field 1-20g, preferred 5.0-15.0g are the solid dispersion system carrier, 10%PvP ethanol liquid is adhesive, solvent method is granulated, choosing grain 30 orders.Made micropill is the gastric solubleness rapid release.The ferrous 0.01g-0.05g that should be of every capsule sulfur acid.
Above-mentioned two kinds of micropills can wrap different color dress respectively and distinguish or do not wrap color dress to show, but heap is done in clinical desired content ratio separately then and mixed filling capsule than consistent.The clinical practice of this dosage form is suitable for the medication of broad-spectrum cancer.
The present invention is illustrated with following embodiment.Pill and coating are the known technology of pharmacy, and following examples are mainly described the prescription of the two release formulations of compound recipe.But the invention is not restricted to following examples:
Embodiment 1
Bromodihydroartemisiand 4g with lactose, starch, the total 15g of magnesium stearate, makes the ball core; Its coating material enteric acrylic acid 3.5g, ethylene diester 0.35g, tween 80 0.5g, Oleum Ricini 2ml, 90% ethanol 100ml; After enteric acrylic acid is dissolved in 80% ethanol, add all the other compositions, carry out coating behind the mixing fully.Choosing grain 30 orders.
Ferrous sulfate 2g, the total 10g of lactose and dextrin is the solid dispersion system carrier, and 10%PvP ethanol liquid is adhesive, and solvent method is granulated, choosing grain 30 orders.
Bromodihydroartemisiand micropill bag color dress, the ferrous sulfate micropill does not wrap coat, does by dose ratio separately and mixes filling capsule.
Embodiment 2
Bromodihydroartemisiand 3.5g with lactose, modified starch, the total 15g of magnesium stearate, makes the ball core; Its sustained release coating material carries out coating with the enteric coating material of commercially available complete water type as the coating material of slow-release micro-pill.
Ferrous sulfate 2g, the total 15g of lactose and dextrin is the solid dispersion system carrier, and 10%PvP ethanol liquid is adhesive, and solvent method is granulated, choosing grain 30 orders.
Bromodihydroartemisiand micropill bag color dress, ferrous sulfate micropill Bao Suyi does by dose ratio separately and to mix filling capsule.
Embodiment 3
Bromodihydroartemisiand 5g with lactose, modified starch, the total 15g of magnesium stearate, makes the ball core; Its coating material enteric acrylic acid 7g, ethylene diester 0.5g, tween 80 1g, Oleum Ricini 4ml, 80% ethanol 100ml; After enteric acrylic acid is dissolved in 80% ethanol, add all the other compositions, carry out coating behind the mixing fully.Choosing grain 30 orders.
Ferrous sulfate 2.5g, the total 12g of lactose and dextrin is the solid dispersion system carrier, and 10%PvP ethanol liquid is adhesive, and solvent method is granulated, choosing grain 30 orders.
Bromodihydroartemisiand micropill and ferrous sulfate micropill are done by dose ratio separately and are mixed filling capsule.
Claims (10)
1. a compound recipe of being made up of Bromodihydroartemisiand and ferrous sulfate is two releases pellet preparations, it is characterized in that: slow-release micro-pill is to make enteric coated again forming behind the ball core by Bromodihydroartemisiand and pharmaceutically acceptable excipient; Ferrous sulfate is then made the gastric solubleness fast release micropill with pharmaceutically acceptable excipient, slow-release micro-pill and fast release micropill is loaded in proportion makes the two capsule preparations of releasing of compound recipe in the common gastric-dissolved capsule shell then.
2. preparation according to claim 1 is characterized in that a kind of compound preparation that contains Bromodihydroartemisiand and ferrous sulfate, and the Bromodihydroartemisiand content in also being to fill a prescription is 1.0-20.g, and ferrous sulfate content is 0.5-10.g.
3. preparation according to claim 1, one or more make the ball core that it is characterized in that the Bromodihydroartemisiand slow-release micro-pill by Bromodihydroartemisiand and lactose, starch, magnesium stearate or various modified starch and acceptable other excipient of pharmaceutical field, and the excipient total amount is 1-30g.
4. preparation according to claim 1, the sustained release coating material that it is characterized in that the Bromodihydroartemisiand slow-release micro-pill are enteric acrylic acid 3-8g, ethylene diester 0.1-1.5g, tween 80 0.1-1.5g, Oleum Ricini 2-4ml, 80-95% ethanol 100ml.
5. preparation according to claim 1 is characterized in that the sustained release coating material of Bromodihydroartemisiand slow-release micro-pill also is fit to the coating of commercially available enteric coating material as slow-release micro-pill.
6. preparation according to claim 1, the every capsule that it is characterized in that the Bromodihydroartemisiand slow-release micro-pill contains the bromo dihydroarteannuin and should be 0.02g-0.08g.
7. preparation according to claim 1, one or more make the ball core that it is characterized in that the ferrous sulfate fast release micropill by ferrous sulfate and acceptable other excipient of lactose, dextrin and pharmaceutical field, and the excipient total amount is 1-20g.
8. preparation according to claim 1 is characterized in that the ferrous 0.01g-0.05g of should be of every capsule sulfur acid of ferrous sulfate fast release micropill.
9. preparation according to claim 1 is characterized in that two kinds of micropill heaps are than consistent.
10. preparation according to claim 1, it is characterized in that two kinds of micropills according to dosage ratio do and mix filling capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101678942A CN102038677A (en) | 2009-10-15 | 2009-10-15 | Brominated dihydroartemisinin compound double-releasing preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101678942A CN102038677A (en) | 2009-10-15 | 2009-10-15 | Brominated dihydroartemisinin compound double-releasing preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102038677A true CN102038677A (en) | 2011-05-04 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101678942A Withdrawn CN102038677A (en) | 2009-10-15 | 2009-10-15 | Brominated dihydroartemisinin compound double-releasing preparation |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012136125A1 (en) * | 2011-04-08 | 2012-10-11 | Shi Yanyu | Compound dual-release capsule formulation comprised of bromodihydroartemisinin and a fe2+ agent |
| CN103181901A (en) * | 2011-12-30 | 2013-07-03 | 桂林南药股份有限公司 | Dihydroartemisinin controlled-release preparation used for treating lupus erythematosus |
| CN104086560A (en) * | 2014-07-03 | 2014-10-08 | 唐心建 | Halogenated artemisinin mother nucleus, halogenated artemisinin derivatives, halogenated dihydroartemisinin and halogenated decarbonylation artemisinin and medical use thereof |
| CN104739824A (en) * | 2013-12-30 | 2015-07-01 | 昆山达人生物医药有限公司 | Use of dihydroartemisinin in preparation of drug for inhibition of tumour growth |
| CN108451976A (en) * | 2018-07-02 | 2018-08-28 | 上海应用技术大学 | A kind of ferrous sulfate pellet and preparation method thereof |
-
2009
- 2009-10-15 CN CN2009101678942A patent/CN102038677A/en not_active Withdrawn
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012136125A1 (en) * | 2011-04-08 | 2012-10-11 | Shi Yanyu | Compound dual-release capsule formulation comprised of bromodihydroartemisinin and a fe2+ agent |
| CN103181901A (en) * | 2011-12-30 | 2013-07-03 | 桂林南药股份有限公司 | Dihydroartemisinin controlled-release preparation used for treating lupus erythematosus |
| CN104739824A (en) * | 2013-12-30 | 2015-07-01 | 昆山达人生物医药有限公司 | Use of dihydroartemisinin in preparation of drug for inhibition of tumour growth |
| CN104086560A (en) * | 2014-07-03 | 2014-10-08 | 唐心建 | Halogenated artemisinin mother nucleus, halogenated artemisinin derivatives, halogenated dihydroartemisinin and halogenated decarbonylation artemisinin and medical use thereof |
| CN108451976A (en) * | 2018-07-02 | 2018-08-28 | 上海应用技术大学 | A kind of ferrous sulfate pellet and preparation method thereof |
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Open date: 20110601 |