CN101485637B - Colchicine framework controlled release tablets or capsules - Google Patents
Colchicine framework controlled release tablets or capsules Download PDFInfo
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- CN101485637B CN101485637B CN2008100659545A CN200810065954A CN101485637B CN 101485637 B CN101485637 B CN 101485637B CN 2008100659545 A CN2008100659545 A CN 2008100659545A CN 200810065954 A CN200810065954 A CN 200810065954A CN 101485637 B CN101485637 B CN 101485637B
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Abstract
The invention discloses a colchicine framework controlled-release tablet or capsule, which comprises colchicines and framework materials having controlled-release function, wherein the framework materials contain hydrophilic polymers of which the weight against the weight of the tablet is at least 20 percent and other pharmaceutic adjuvants; and the tablet or capsule comprises the following components in percentage by weight: 0.01 to 1.0 percent of colchicine, 20 to 85 percent of hydrophilic polymer, 1 to 30 percent of retarder, 20 to 60 percent of bulking agent, and 0.1 to 2 percent of lubricant. Release degree test results show that more than 90 percent of drugs are continuously released in vitro in 12 hours; and compared with the common tablet, the tablet or capsule has the advantages of obviously reducing daily taking frequency, lowering toxic and side effects of the drugs and improving the compliance and curative effect of patients.
Description
Technical field
The present invention relates to contain the pharmaceutical preparation of colchicine, more particularly, relate to a kind of Colchicine framework controlled release tablets or capsule preparations.
Background technology
Colchicine is known a kind of medicine that can be used for treating gout and anticancer field.Granulocytic infiltration and phagocytic function when colchicine can suppress the gout outbreak, to the selective antiinflammation of acute gouty arthritis, with resolution of symptoms such as red, swollen, hot, the pains in a few hours joint, back, present colchicine is still the most effective medicine for the treatment of the acute hair of gout; At anticancer aspect, by suppressing the mitosis of cell, treat leukemia, breast carcinoma etc., sphere of learning is found in recent years, colchicine also can be used for treating liver cirrhosis.The colchicine toxic and side effects is big, mainly contain digestive tract reaction, liver injury, kidney damage, bone marrow toxicity reaction, alopecia, spirit depressing, anorexia, numbness of hands and feet etc., visible gastroenteritis haemorrhagica, nausea,vomiting,diarrhea when excessive, severe patient can be suffered a shock deadly.
Colchicine is oral through gastrointestinal absorption, reaches peak concentration in 0.5-2 hour, and half-life 20-60 minute, plasma protein binding rate was low, and medicine storage time in tissue is long, and the half-life in granulocyte is 46 hours.Common oral administration: maximum dose 1mg first, later on every 2 hours administration 0.5mg, up to pain relief, as gastrointestinal reactions such as serious vomiting, diarrhoea appear, drug withdrawal immediately, and so repeatedly, need every day repeatedly frequently to take medicine, add to be prone to gastrointestinal reaction that patient's compliance is low.
Low, serious gastrointestinal reaction, the patient's compliance of therapeutic index is low etc., and reason makes the clinical practice of colchicine bone be subjected to great restriction, makes its clinical application be far from bringing into play.Research and develop new dosage form, make things convenient for patient to take medicine, alleviate the important topic that toxic and side effects is just becoming this area.
In order to obtain more stable blood drug level, reduce gastrointestinal side effect, to be convenient to medication, domestic existing (1) colchicine osmotic pump tablet (CN 1692902A), (2) microcapsule (CN 1695603A), (3) patch (1165652A), oral and external preparation patent application such as (4) cataplasma (1568951A).
But also there are some defectives in existing patented technology, as: wherein (1) adopts the osmotic pumps technology to obtain external constant speed release medicine, but limit by the dissolubility of colchicine itself and dosage, and its cumulative release degree can not reach the pharmacopeia requirement.(2) fail to solve preferably the multiple dosing of this product.(3) and (4) avoided gastrointestinal irritation by external, but also the preparation indication is confined to gout.
Summary of the invention
The technical problem that the present invention solves provides a kind ofly to be had stable rate of releasing drug and higher cumulative release rate, can obtain more stable blood drug level level after taking, effectively reduces patient's medicining times and also can reduce toxic and side effects, safe Colchicine framework controlled release tablets or capsule.
Technical scheme of the present invention is: a kind of Colchicine framework controlled release tablets or capsule, it contains: colchicine, pharmaceutic adjuvant and the framework material that plays the controlled release effect, described pharmaceutic adjuvant comprises blocker, disintegrating agent, lubricant, coloring agent and filler, it is characterized in that: each component accounts for the heavy percentage by weight of sheet and is respectively:
Colchicine 0.01%-1.0%,
Disintegrating agent 0-20%,
Filler, lubricant, coloring agent surplus.
Each component accounts for the heavy percentage by weight of sheet and is respectively:
Colchicine 0.333%,
Blocker 13.33%
Lubricant 1.33%,
Coloring agent 0.333%,
Filler 44.674%.
Described framework material is selected from Lac, gelatin or sodium alginate.Also can select cellulose derivative for use,, perhaps select crylic acid resin for use, as EUDRAGIT NE 30 D EUDRAGIT NE 30D etc. as ethyl cellulose, hydroxypropyl cellulose, cellulose acetate etc.; Can also select polyethylene based polymers for use, as polyvinyl alcohol, crospolyvinylpyrrolidone etc.
Preferred framework material of the present invention is selected polyoxyethylene for use; Described blocker is selected sodium carboxymethyl cellulose for use; Described disintegrating agent is selected cross-linking sodium carboxymethyl cellulose for use; Described filler is selected microcrystalline Cellulose for use; Described lubricant is selected magnesium stearate for use; Described coloring agent is selected iron oxide red for use.
Framework material comprises in described or the capsule: accounting for the heavy percentage by weight of sheet and be 40% polyoxyethylene WSR-303 and accounting for the heavy percentage by weight of sheet is 13.33% carmethose.
Framework material comprises in described or the capsule: accounting for the heavy percentage by weight of sheet and be 40% hydroxypropyl first fiber K15M and accounting for the heavy percentage by weight of sheet is 13.33% carmethose.
Framework material comprises in described or the capsule: accounting for the heavy percentage by weight of sheet and be 40% polyoxyethylene WSR-303 and accounting for the heavy percentage by weight of sheet is 13.33% polyoxyethylene N-60K.
Framework material comprises in described or the capsule: accounting for the heavy percentage by weight of sheet and be 40% hypromellose K15M and accounting for the heavy percentage by weight of sheet is 13.33% hypromellose K4M.
Framework material comprises in described or the capsule: accounting for the heavy percentage by weight of sheet and be 10% hypromellose K100M and accounting for the heavy percentage by weight of sheet is 43.33% hypromellose K4M.
Framework material comprises in described or the capsule: accounting for the heavy percentage by weight of sheet and be 30% polyoxyethylene WSR-303 and accounting for the heavy percentage by weight of sheet is 23.33% polyoxyethylene N-60K.
Framework material comprises in described or the capsule: accounting for the heavy percentage by weight of sheet and be 40% polyoxyethylene WSR-303 and accounting for the heavy percentage by weight of sheet is 13.33% carmethose.
Framework material comprises in the described controlled release tablet: accounting for the heavy percentage by weight of sheet and be 40% hypromellose K15M and accounting for the heavy percentage by weight of sheet is 13.33% carmethose.
Framework material comprises in described or the capsule: accounting for the heavy percentage by weight of sheet and be 40% polyoxyethylene WSR-303 and accounting for the heavy percentage by weight of sheet is 13.33% polyoxyethylene N-60K.
Colchicine framework controlled release tablets of the present invention or capsule have following beneficial effect: have comparatively stable rate of releasing drug and higher cumulative release rate after Colchicine framework controlled release tablets of the present invention or capsule are taken medicine, can effectively reduce patient's medicining times, improve patient's compliance, improve drug safety, guarantee the therapeutic effect of this medicine.
Description of drawings:
Fig. 1 is Colchicine framework controlled release tablets of the present invention or capsular preparation technology's flow chart
Fig. 2 is Colchicine framework controlled release tablets of the present invention or the capsule different amounts polyoxyethylene influence curve to the framework controlled release tablets release;
Fig. 3 is Colchicine framework controlled release tablets of the present invention or the capsular different amounts sodium carboxymethyl cellulose influence curve figure to the matrix tablet release;
Fig. 4 is Colchicine framework controlled release tablets of the present invention or the capsular different amounts cross-linking sodium carboxymethyl cellulose influence curve figure to the matrix tablet release;
Fig. 5 is Colchicine framework controlled release tablets of the present invention or the capsular different amounts sodium chloride influence curve figure to the matrix tablet release;
Fig. 6 is Colchicine framework controlled release tablets of the present invention or the capsular different amounts filler influence curve figure to the matrix tablet release;
Fig. 7 is Colchicine framework controlled release tablets of the present invention or the capsular different framework material influence curve to release, and wherein curve is defined as follows:
1-hypromellose K15M/60+ hypromellose K4M/20;
2-polyoxyethylene 700/60+ polyoxyethylene 200/20;
3-hypromellose K100M/15+ hypromellose K4M/65
4-polyoxyethylene 700/60+ sodium carboxymethyl cellulose/20;
5-polyoxyethylene 700/45+ polyoxyethylene 200/35;
6-hypromellose K15M/60+ carmethose/20.
The specific embodiment:
Research process and parameter below by Colchicine framework controlled release tablets or the design of capsular prescription are selected according to the present invention will be described in more detail.
The framework controlled release technology is meant that medicine and one or more inert solid framework materials make lamellar, granule or other forms of preparation by compacting or integration technology, and commonly used is matrix tablet.According to the difference of framework material, generally be divided into hydrogel matrix, bioerodable skeleton and insoluble skeleton.Technology of the present invention relates to hydrophilic gel framework controlled release tablets or capsule.
The evaluation methodology that this paper adopts is release detection method (2005 editions two appendix X D of Chinese Pharmacopoeia) first method.
Concrete operation method
Release is checked: little agar diffusion method, dissolution medium is the purified water of the degassing, 100 rev/mins, 37 ℃ ± 1 ℃.
Detection method: the HPLC method, the C18 chromatographic column, wavelength 245nm, 30 ℃ of column temperatures, methanol-0.05mol/L phosphate buffer (pH5.4) (47.5: 52.5) is a mobile phase, flow velocity 1ml/min.
1. Colchicine framework controlled release tablets of the present invention or capsular preparation technology's flow process are as shown in Figure 1.
2. single factor screening
With reference to pertinent literature report, this paper under the prerequisite of fixing tablet forming technique parameter, high spot reviews label write out a prescription and external release condition to the influence of Colchicine framework controlled release tablets or capsule drug release behavior.
The test of intending in the experimentation adopting is write out a prescription as follows substantially:
Prescription: colchicine (Colchicine) 0.5mg
Iron oxide red (Ferric oxide) 0.5mg
Polyoxyethylene (POLYOX WSR303) 50.0mg
Sodium carboxymethyl cellulose (CMCNa) 20.0mg
Cross-linking sodium carboxymethyl cellulose (CMS) 6.0mg
Microcrystalline Cellulose (MCC) 71.0mg
Magnesium stearate (Mg-S) 2.0mg
Amount to 150mg
Except that specifying, the technique for fixing parameter is as follows in the experimentation: the tablet machine punch die is dimple form (Φ=0.8mm); Label hardness 50-70N, the heavy 150mg of sheet ± 2%.
2.1 the influence of polyoxyethylene consumption
The consumption of other component in the fixed prescription, the consumption of adjustment high molecular weight hydrophilic polymer polyoxy ethylene, and alternative with the equivalent microcrystalline Cellulose.To investigate the influence of polyoxyethylene to drug release behavior.Its prescription design sees Table 1.
The prescription design of the different polyoxyethylene consumptions of table 1
The different amounts polyoxyethylene to the influence (n=3) of matrix tablet release as shown in Figure 2.
Measure the release of matrix tablet in 12h according to the drug release determination method, the results are shown in Figure 2.Show that the different amounts polyoxyethylene is influential to drug release.
Conclusion: as seen from the figure, the polyoxyethylene consumption is big more, and the rate of releasing drug of matrix tablet is slow more.
2.2 the influence of sodium carboxymethyl cellulose consumption
The fixed prescription total amount, with sodium carboxymethyl cellulose as blocker, with the carmethose equivalent substitution microcrystalline Cellulose of different amounts.To investigate of the influence of carmethose consumption to drug release behavior.Its prescription design sees Table 2.
The prescription design of the different carmethose consumptions of table 2
The different amounts carmethose to the influence (n=3) of matrix tablet release as shown in Figure 3.
Measure the release of matrix tablet in 12h according to the drug release determination method, the results are shown in Figure 3.Show that the different amounts carmethose is influential to drug release.
Conclusion: as seen from the figure, the carmethose consumption is big more, and the rate of releasing drug of matrix tablet is slow more.
2.3 the influence of cross-linking sodium carboxymethyl cellulose consumption
The fixed prescription total amount, with cross-linking sodium carboxymethyl cellulose as disintegrating agent, with the cross-linking sodium carboxymethyl cellulose equivalent substitution microcrystalline Cellulose of different amounts.To investigate of the influence of cross-linking sodium carboxymethyl cellulose consumption to drug release behavior.Its prescription design sees Table 3.
The prescription design of the different cross-linked carboxymethyl cellulose sodium consumptions of table 3
Different amounts cross-linked carboxymethyl cellulose sodium to the influence (n=3) of matrix tablet release as shown in Figure 4.
Measure the release of matrix tablet in 12h according to the drug release determination method, the results are shown in Figure 4.Show that the different amounts cross-linking sodium carboxymethyl cellulose is little to the drug release influence, can be among the we without disintegrating agent.
2.4 the influence of sodium chloride consumption
The fixed prescription total amount, with sodium chloride as penetrating agent, with the sodium chloride equivalent substitution microcrystalline Cellulose of different amounts.To investigate of the influence of sodium chloride consumption to drug release behavior.Its prescription design sees Table 4.
The prescription design of the different sodium chloride consumptions of table 4
Different amounts sodium chloride to the influence (n=3) of matrix tablet release as shown in Figure 5.
Measure the release of matrix tablet in 12h according to the drug release determination method, the results are shown in Figure 5.Show that different amounts sodium chloride is little to the drug release influence, can be among the we without penetrating agent.
2.5 the influence of other adjuvant
The fixed prescription total amount is that filler, polyoxyethylene are hydrophilic gel material with the Celluloasun Microcrystallisatum, investigates the influence of other adjuvant to drug release behavior.Its prescription design sees Table 5.
The prescription design of other adjuvant of table 5
Other adjuvant to the influence (n=3) of matrix tablet release as shown in Figure 6.
Measure the release of matrix tablet in 12h according to the drug release determination method, the results are shown in Figure 6.The existence that shows other adjuvant is influential to drug release.
Conclusion: as seen from the figure, add the drug release behavior that an amount of carmethose and cross-linking sodium carboxymethyl cellulose can be regulated matrix tablet in the prescription.
2.6 the influence of framework material kind
Each supplementary product consumption of fixed prescription is investigated the influence of different framework materials such as carmethose, hypromellose, polyoxyethylene to drug release behavior.Its prescription design sees Table 6.
The prescription design of the different framework materials of table 6
The framework material kind to the influence (n=3) of release as shown in Figure 7.
Measure the release of matrix tablet in 12h according to the drug release determination method, the results are shown in Figure 7.
Hypromellose K15M/60+ hypromellose K4M/20 the results are shown in curve 1;
Polyoxyethylene 700/60+ polyoxyethylene 200/20 the results are shown in curve 2;
Hypromellose K100M/15+ hypromellose K4M/65 the results are shown in curve 3
Polyoxyethylene 700/60+ sodium carboxymethyl cellulose/20 the results are shown in curve 4;
Polyoxyethylene 700/45+ polyoxyethylene 200/35 the results are shown in curve 5;
Hypromellose K15M/60+ carmethose/20 the results are shown in curve 6.
Above result shows that the type of framework material has very big influence to drug release, wherein adopts 60mg polyoxyethylene 700 and sodium carboxymethyl cellulose 20mg person's release curve linear relation and final cumulative release rate better.
To sum up test, drawing best prescription is colchicine 0.5mg, iron oxide red 0.5mg, 60mg polyoxyethylene WSR-303 (7,000,000), sodium carboxymethyl cellulose 20mg, microcrystalline Cellulose 67mg, magnesium stearate 2mg.
3. the influence factor of selected prescription test
Prepare a collection of test sample (070901 batch) by above-mentioned preferred prescription, simulation listing packing (plastic-aluminum aluminum packing, 6 is on chip).During test sample is removed unlap and puts into surface plate, place by following condition:
(1) hot test: sample was placed 10 days under 60 ℃ of constant temperatures.
(2) high wet test: sample was placed 10 days under RH75% ± 5% condition at 25 ℃.
(3) exposure experiments to light: sample was placed 10 days under 4500Lx ± 500Lx illumination conditions.
Respectively at sampling in the 0th, 5,10 day, check indexs such as release, content, moisture, outward appearance, and with the 0th day relatively.
Result of the test shows: exposure experiments to light is bigger to sample effects, having good stability under other influence factor's experimental conditions.Therefore, this product should keep in Dark Place.The results are shown in Table 7-9.
Table 7 high temperature (60 ℃) result of the test
| Test period (d) | Character | Content (%) | Release (%) 12h | Moisture (%) | |
| 0 | Pale red color chips | 97.6 | 96.1 | 0.1 | 0.5 |
| 5 | Pale red color chips | 94.4 | 94.9 | 0.1 | 0.4 |
| 10 | Pale red color chips | 95.2 | 94.2 | 0.1 | 0.5 |
Table 8 high humidity (RH=75% ± 5%) result of the test
| Test period (d) | Character | Content (%) | Release (%) 12h | Moisture (%) | |
| 0 | Pale red color chips | 97.6 | 96.1 | 0.1 | 0.5 |
| 5 | Pale red color chips, sticking shape | 93.8 | 77.6 | 9.7 | 0.5 |
| 10 | Light red is glued dough | 94.6 | 66.9 | 12.6 | 0.3 |
Table 9 illumination (4500 ± 500Lx) result of the tests
| Test period (d) | Character | Content (%) | Release (%) 12h | Moisture (%) | |
| 0 | Pale red color chips | 97.6 | 96.1 | 0.1 | 0.5 |
| 5 | Pale red color chips | 67.3 | 58.4 | 0.1 | 0.5 |
| 10 | Pale red color chips | 56.9 | 43.8 | 0.1 | 0.4 |
4. the preparation of pilot product
According to the prescription of optimization, in three batches of Colchicine framework sheet (lot numbers: 071001,071002,071003), 10000 every batch, the results are shown in Table 10 of our company's preparation.
Table 10 pilot plant test result
Result of the test shows constant product quality, feasible process.
Embodiment 1:
Prescription: colchicine 0.15g
Polyoxyethylene WSR303 375g
Sodium carboxymethyl cellulose 450g
Cross-linking sodium carboxymethyl cellulose 150g
Microcrystalline Cellulose 507.85g
Magnesium stearate 15g
Ferrum oxide 2g
Make 10000
Preparation method: a. according to equivalent incremental method mixing, makes mixture with colchicine, hydrophilic polymer, other pharmaceutic adjuvants;
B. mixture is mixed and made into soft material with alcoholic solution, add alcoholic solution amount agglomerating, the degree of being that promptly looses waved pinched with the soft material that makes; Followed 22 mesh sieves and granulated, obtained wet granular, wet granular in 40 ℃ times dry 5 hours, was obtained dried granule; Then, obtain drug particles with 20 mesh sieve granulate;
C. the granule with b step gained adds the magnesium stearate mixing; The tablet machine punch die is dimple form (Φ=0.8mm); Carry out tabletting, extrusion forming gets final product; Label hardness 50-70N, the heavy 150mg of sheet ± 2%.
Embodiment 2:
Prescription: colchicine 12g
Polyoxyethylene WSR303 1275g
Sodium carboxymethyl cellulose 15g
Microcrystalline Cellulose 181g
Magnesium stearate 15g
Make 10000
Preparation method: a. according to equivalent incremental method mixing, makes mixture with colchicine, hydrophilic polymer, other pharmaceutic adjuvants;
B. mixture is mixed and made into soft material with alcoholic solution, add alcoholic solution amount agglomerating, the degree of being that promptly looses waved pinched with the soft material that makes; Followed 22 mesh sieves and granulated, obtained wet granular, wet granular in 40 ℃ times dry 5 hours, was obtained dried granule; Then, obtain drug particles with 20 mesh sieve granulate;
C. the granule with b step gained adds the magnesium stearate mixing, and is encapsulated.
Embodiment 3:
Prescription: colchicine 15g
Polyoxyethylene WSR303 800g
Sodium carboxymethyl cellulose 200g
Cross-linking sodium carboxymethyl cellulose 300g
Microcrystalline Cellulose 168g
Magnesium stearate 15g
Ferrum oxide 2g
Make 10000
Preparation method: with embodiment 1.
Embodiment 4:
Prescription: colchicine 15g
Polyoxyethylene WSR303 300g
Sodium carboxymethyl cellulose 400g
Cross-linking sodium carboxymethyl cellulose 300g
Microcrystalline Cellulose 468g
Magnesium stearate 15g
Ferrum oxide 2g
Make 10000
Preparation method: with embodiment 1.
Embodiment 5:
Prescription: colchicine 4.995g
Polyoxyethylene WSR303 600g
Sodium carboxymethyl cellulose 200g
Cross-linking sodium carboxymethyl cellulose 0
Microcrystalline Cellulose 670.11g
Magnesium stearate 19.95g
Ferrum oxide 4.995g
Make 10000
Preparation method: with embodiment 1.
Claims (4)
1. Colchicine framework controlled release tablets, it contains: colchicine, pharmaceutic adjuvant and the framework material that plays the controlled release effect, described pharmaceutic adjuvant comprises blocker, disintegrating agent, lubricant, coloring agent and filler, it is characterized in that: each component accounts for the heavy percentage by weight of sheet and is respectively:
Colchicine 0.01%-1.0%,
Framework material 20%-85%,
Blocker 1%-30%,
Disintegrating agent 0-20%,
Filler, lubricant, coloring agent surplus;
Described framework material is selected polyoxyethylene for use, and described blocker is selected sodium carboxymethyl cellulose for use.
2. Colchicine framework controlled release tablets, it contains: colchicine, pharmaceutic adjuvant and the framework material that plays the controlled release effect, described pharmaceutic adjuvant comprises blocker, disintegrating agent, lubricant, coloring agent and filler, it is characterized in that: each component accounts for the heavy percentage by weight of sheet and is respectively:
Colchicine 0.01%-1.0%,
Framework material 20%-85%,
Blocker 1%-30%,
Disintegrating agent 0-20%,
Filler, lubricant, coloring agent surplus;
Described blocker is selected sodium carboxymethyl cellulose for use;
Described framework material is to comprise: accounting for the heavy percentage by weight of sheet and be 40% polyoxyethylene WSR-303 and accounting for the heavy percentage by weight of sheet is 13.33% carmethose,
Or be to comprise: accounting for the heavy percentage by weight of sheet and be 40% hydroxypropyl first fiber K15M and accounting for the heavy percentage by weight of sheet is 13.33% carmethose,
Or be to comprise: accounting for the heavy percentage by weight of sheet and be 40% polyoxyethylene WSR-303 and accounting for the heavy percentage by weight of sheet is 13.33% polyoxyethylene N-60K,
Or be to comprise: accounting for the heavy percentage by weight of sheet and be 40% hypromellose K15M and accounting for the heavy percentage by weight of sheet is 13.33% hypromellose K4M,
Or be to comprise: accounting for the heavy percentage by weight of sheet and be 10% hypromellose K100M and accounting for the heavy percentage by weight of sheet is 43.33% hypromellose K4M,
Or be to comprise: accounting for the heavy percentage by weight of sheet and be 30% polyoxyethylene WSR-303 and accounting for the heavy percentage by weight of sheet is 23.33% polyoxyethylene N-60K.
3. Colchicine framework controlled release tablets according to claim 1 is characterized in that: each component accounts for the heavy percentage by weight of sheet and is respectively:
Colchicine 0.333%,
Framework material 40%,
Blocker 13.33%,
Lubricant 1.33%,
Coloring agent 0.333%,
Filler 44.674%.
4. according to claim 1 or 3 described Colchicine framework controlled release tablets, it is characterized in that: described disintegrating agent is selected cross-linking sodium carboxymethyl cellulose for use; Described filler is selected microcrystalline Cellulose for use; Described lubricant is selected magnesium stearate for use; Described coloring agent is selected iron oxide red for use.
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| US11877991B2 (en) | 2018-02-02 | 2024-01-23 | Murray And Poole Enterprises Ltd | Use of colchicine to inhibit tumor growth and metastases |
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| DK2914255T3 (en) | 2012-11-02 | 2021-10-25 | Murray & Poole Entpr Ltd | TREATMENT OR PREVENTION OF CARDIOVASCULAR EVENTS VIA ADMINISTRATION OF COLCHICIN |
| AU2014255434B2 (en) | 2013-04-16 | 2018-11-08 | Murray And Poole Enterprises Limited | Sustained-release formulations of colchicine and methods of using same |
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|---|---|---|---|---|
| RO63556A2 (en) * | 1974-04-13 | 1978-07-15 | Medicamente Intreprinderea De | ORAL TABLETS WITH COLQUICINE |
| RO63829A2 (en) * | 1975-02-18 | 1979-01-15 | Medicamente Intreprinderea De | ORCHILICAL TABLETS WITH COLCHICINE |
| CN1692902A (en) * | 2004-11-12 | 2005-11-09 | 普尔药物科技开发（深圳）有限公司 | Colchicine osmosis pump tablet, and its prepn. method |
| US7265248B1 (en) * | 2005-04-29 | 2007-09-04 | Technology Innovations, Llc | Compositions and methods for the treatment of malaria |
-
2008
- 2008-01-18 CN CN2008100659545A patent/CN101485637B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RO63556A2 (en) * | 1974-04-13 | 1978-07-15 | Medicamente Intreprinderea De | ORAL TABLETS WITH COLQUICINE |
| RO63829A2 (en) * | 1975-02-18 | 1979-01-15 | Medicamente Intreprinderea De | ORCHILICAL TABLETS WITH COLCHICINE |
| CN1692902A (en) * | 2004-11-12 | 2005-11-09 | 普尔药物科技开发（深圳）有限公司 | Colchicine osmosis pump tablet, and its prepn. method |
| US7265248B1 (en) * | 2005-04-29 | 2007-09-04 | Technology Innovations, Llc | Compositions and methods for the treatment of malaria |
Non-Patent Citations (2)
| Title |
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| 李桂枝，等.荧光法测定片剂中的秋水仙碱.《分析试验室》.1999,第18卷(第3期), |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11877991B2 (en) | 2018-02-02 | 2024-01-23 | Murray And Poole Enterprises Ltd | Use of colchicine to inhibit tumor growth and metastases |
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