CN1985808A - Carbazochrome sodium sulfonate slow-released tablet and its preparing method - Google Patents
Carbazochrome sodium sulfonate slow-released tablet and its preparing method Download PDFInfo
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- CN1985808A CN1985808A CNA2006101662067A CN200610166206A CN1985808A CN 1985808 A CN1985808 A CN 1985808A CN A2006101662067 A CNA2006101662067 A CN A2006101662067A CN 200610166206 A CN200610166206 A CN 200610166206A CN 1985808 A CN1985808 A CN 1985808A
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- sodium sulfonate
- slow
- carbazochrome sodium
- released
- carbazochrome
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Abstract
The present invention is slow released carbazochrome sodium sulfonate matrix tablet and its preparation process. The recipe of the slow released carbazochrome sodium sulfonate matrix tablet includes carbazochrome sodium sulfonate 5-85 wt%, matrix material 10-90 wt%, diluent 0-80 wt%, and proper amount of adhesive and lubricant. It is prepared through mixing material powder and direct tabletting; or pelletizing the mixture of materials except lubricant, mixing with lubricant and tabletting; or preparing fast release part, preparing slow releasing part and double-layered tabletting. The pelletizing may be wet pelletizing, dry pelletizing, smelting palletizing, etc.
Description
Technical field:
The invention belongs to the technical field of medicament slow release preparation, exactly relate to a kind of sustained-release matrix tablets that contains the active component carbazochrome sodium sulfonate and preparation method thereof.
Technical background:
The carbazochrome sodium sulfonate chemical name is: 1-methyl-6-oxo-2,3,5, and 6-tetrahydro indole-5-semicarbazone-2-sodium sulfonate, molecular weight 376.32, structural formula is as follows:
Carbazochrome sodium sulfonate is easily molten in hot water, and is molten in the water part omitted, almost insoluble in ethanol or chloroform.
Carbazochrome sodium sulfonate is to be that the basis is modified and got with the carbazochrome salicylate structure, and water solublity strengthens 50 times, and this is very beneficial for the preparation of slow releasing preparation, and haemostatic effect is also more excellent.
Carbazochrome sodium sulfonate is a blood vessel hardening agent of new generation, can increase the resistance of blood capillary to damage, reduces the permeability of blood capillary, promotes the retraction of blood capillary fracture end and stops blooding.
Pharmacokinetic shows, behind the oral carbazochrome sodium sulfonate 150mg of the man of health adult, Cmax reaches 25ng/ml in 0.5～1 hour blood, and the half-life (t1/2) is 1.5 hours, it is the highest that oral back reached urine Chinese medicine concentration in 0.5～1 hour, and drainage in about 24 hours finishes.
The carbazochrome sodium sulfonate anastalsis is fast, and is applied widely, and pneumorrhagia (spitting of blood, bloody sputum), digestive tract hemorrhage (hematemesis, melena), nephrorrhagia, hematuria, childbirth and postpartum hemorrhage, menorrhagia, epistaxis, gingiva bleeding gingival hemorrhage etc. are all had obvious curative effects; The postoperative hemorrhage of various wound hemorrhages and breast, stomach, urinary tract and department of obstetrics and gynecology, all diseases of department of eye and oozing of blood etc. all there are preventive and therapeutic effect,, have significant haemostatic effect especially at the popularity oozing of blood that cooperates organ transplantation (for example renal transplantation) postoperative.
Following clinical research summary main reference document " new carbazochrome salicylate of hemorrhage and application thereof " (Liao Qingjiang, Chinese Journal of New Drugs, 1993 the 2nd the 6th phases of volume, 24～25 pages).
1. domestic clinical research
Carbazochrome sodium sulfonate injection and oral tablet through Shanghai, 15 hospitals in ground such as Tianjin, Nanjing, Suzhou, Changzhou to various types of bleeding patients the clinical verification of totally 450 examples show, its haemostatic effect produce effects person 197 examples (accounting for 43.77%), responder's 186 examples (accounting for 41.33%), total effective rate 85.10%, nonresponder's 67 examples (accounting for 14.90%).
2. foreign data introduction
Some external data have been introduced the following purposes of carbazochrome sodium sulfonate except that hemostasis:
Because of the chilblain that the peripheral vessel resistance descends and to cause, injectable 2ml/d, continuously or the next day administration after, the peripheral vessel resistance significantly increases, and consciously can alleviate rapidly with the objective sign shape.
Because of the anaphylactoid purpura that the blood capillary fragility causes, inject 2～4ml day after day, can improve capillary resistance and shorten the subcutaneous hemorrhage time, and subcutaneous hemorrhage and ecchymosis are reduced or disappear.
To allergic diseases such as bronchial asthma etc., can utilize the antihistamine effect of carbazochrome sodium sulfonate to reduce dyspnea, and outbreak is alleviated or disappear.Urticaria, eczema also can very fast healings after medication, and scratchiness disappears.
As the blood vessel hardening agent, cerebrovascular (arteriole, blood capillary) for arteriosclerosis or hyperpietic all shows invigoration effect, in 3～4 weeks of beginning, 120mg/d, later use maintenance dose 30mg/d, can prevent blood capillary to break and prevent that blood from oozing out, the fragile disease of the blood capillary during treatment hypertension, both be applicable to the treatment behind the cerebral hemorrhage, but the outbreak of prevention of brain apoplexy again.
The existing dosage form of carbazochrome sodium sulfonate has tablet (trade name: Luo Ye), injection etc.As everyone knows, the patient uses injection very inconvenient, and compliance is very poor.When taking the carbazochrome sodium sulfonate sheet, contact with gastrointestinal mucosa with high concentration after the medicine stripping, easily produce zest, so can produce untoward reaction such as inappetence, stomach discomfort, nausea and vomiting; It only is 1.5 hours because of its biological half-life again, so the intravital effective blood drug concentration in oral back is held time very short, the patient need take 3～4 every day, thereby compliance is also relatively poor, especially take medicine evening the back to morning interval long, blood drug level is very low during early morning, " peak valley " phenomenon appears, drug effect can not be brought into play stably, and the toxic and side effects that causes is also big, therefore considers the development carbazochrome sodium sulfonate slow-released tablet.
Summary of the invention:
An object of the present invention is to overcome the shortcoming and defect of above-mentioned prior art, provide a kind of haemostatic effect more lasting, toxic and side effects is lower, and medicining times is few, the carbazochrome sodium sulfonate slow-released tablet agent with the framework material control drug release of good patient compliance.
Another object of the present invention provides a kind of preparation method of carbazochrome sodium sulfonate slow-released matrix tablet.
Carbazochrome sodium sulfonate slow-released tablet of the present invention is made up of crude drug, framework material, diluent, binding agent and lubricant.
Prescription composition of carbazochrome sodium sulfonate slow-released tablet of the present invention and preparation method thereof is as follows:
1, prescription is formed (g/g):
Carbazochrome sodium sulfonate 5%～85%
Framework material 10%～90%
Diluent 0～80%
Binding agent is an amount of
Lubricant is an amount of
2, preparation method:
The preparation method of carbazochrome sodium sulfonate slow-released tablet of the present invention comprises: will be formed by direct compression of full-powder behind the supplementary material mixing; Or make tablet with lubricant mixing repress after supplementary material made granule; Or get part material medicine and auxiliary materials and mixing earlier, and make immediate release section, surplus stock medicine, framework material and diluent mixing as slow-released part, are pressed into the bilayer tablet that has release layer and slow release layer simultaneously; Method of granulating comprises dry method, wet method, fusing or fusion etc.
The adjuvant of carbazochrome sodium sulfonate slow-released tablet of the present invention is as follows:
Framework material can be a cellulose derivative, as ethyl cellulose, methylcellulose, hyprolose, hypromellose, carboxymethyl cellulose etc.; Can be biodegradation material, comprise materials such as waxiness, fatty acid and esters thereof, as stearic acid, glyceryl monostearate, Brazil wax, octadecanol, hexadecanol, Tridocosanoin etc.; Can be acrylic polymer, as carbomer, Carbopol
, acrylic resin etc.; Can also be that other has the material that delays the drug release effect, as sodium alginate, guar gum, pectin, modified starch, chitosan, polyvinyl alcohol, polyethylene, polypropylene, polysiloxanes etc.; Various framework materials also can mix use and make mixed matrix type slow releasing tablet.
Diluent comprises one or more mixing wherein such as microcrystalline Cellulose, each kind of starch, lactose, sucrose, mannitol, preferred pregelatinized Starch and lactose; Diluent also comprises the material of scalable drug release rate such as porogen etc., as fructose, sorbitol, sodium chloride, Polyethylene Glycol, polyvidone, surfactant etc.
Binding agent comprises the mixed solution, hypromellose, polyvidone, methylcellulose, ethyl cellulose of water or alcohol, water and alcohol etc.;
Lubricant is magnesium stearate or calcium, Pulvis Talci, micropowder silica gel, sodium lauryl sulphate or magnesium etc.
Carbazochrome sodium sulfonate slow-released tablet of the present invention, medicine can continue to discharge more than 5 hours, and effective blood drug concentration can be kept 12 hours.
Carbazochrome sodium sulfonate slow-released tablet of the present invention can be made the cut sheet, so better divided dose.
The carbazochrome sodium sulfonate slow-released tablet that makes according to the present invention has following drug release characteristics in water, pH6.8 and 7.2 buffer (according to the preparation of Chinese Pharmacopoeia method) or mimic physiological environment (in the simulated gastric fluid 1～2 hour, change simulated intestinal fluid again over to):
Time (hour) cumulative release amount %
1 ≤40％
2 ≤60％
4 ≤90％
8 ≥70％
The specific embodiment
Following examples all feed intake by 1000, and specification is decided to be 30mg.Certainly, through clinical experiment, specification also can be decided to be 15mg in addition, 20mg, and 25mg, 35mg, 40mg or other specification, these needs change that sheet heavily gets final product.That is to say that following examples just describe, do not limit scope of invention.
Embodiment 1 carbazochrome sodium sulfonate hydrogel matrix tablet
Prescription:
Carbazochrome sodium sulfonate 30g
HPMC?K4M 50g
Lactose 80g
95% ethanol is an amount of
Magnesium stearate 1.5g
Pulvis Talci 1.5g
Preparation technology:
Card taking network sulphur sodium raw materials medicine, pulverizing is also crossed 120 mesh sieves, with HPMC K4M and lactose mix homogeneously, with granulating after the 95% ethanol moistening, at 50 ℃ of dry back granulate, adds magnesium stearate and Pulvis Talci, the mix homogeneously tabletting.
The release experiment is with two appendix XC first subtraction units of Chinese Pharmacopoeia version in 2005, according to the release of two appendix XD first method working samples of Chinese Pharmacopoeia version in 2005.Be solvent with dilute hydrochloric acid (9 → 1000) 900ml earlier, rotating speed 100 changes, sampling in 1 and 2 hour, the buffer salt 900ml that is changed to pH6.8 then is a solvent, with the method operation, sampling in 4 and 8 hours, according to spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2005), measure trap at 363nm wavelength place, the release of calculation sample, the result is as follows:
Time (hour) cumulative release degree %
1 30.7％
2 43.5％
4 68.2％
8 93.4％
Embodiment 2 carbazochrome sodium sulfonate waxiness matrix tablets
Prescription:
Carbazochrome sodium sulfonate 30g
Octadecanol 30g
Lactose 90g
Magnesium stearate 1.5g
Pulvis Talci 1.5g
Preparation technology:
Card taking network sulphur sodium raw materials medicine, pulverizing is also crossed 120 mesh sieves, with the lactose mix homogeneously, fused octadecanol is added wherein, granulates behind the mixing, adds magnesium stearate and Pulvis Talci, the mix homogeneously tabletting.
The release experiment is with embodiment 1, and the result is as follows:
Time (hour) cumulative release degree %
1 26.8％
2 39.3％
4 65.1％
8 94.3％
Embodiment 3 carbazochrome sodium sulfonate are erodible matrix not
Prescription:
Carbazochrome sodium sulfonate 30g
Ethyl cellulose 45g
Lactose 75g
95% ethanol is an amount of
Magnesium stearate 1.5g
Pulvis Talci 1.5g
Preparation technology:
Card taking network sulphur sodium raw materials medicine, pulverizing is also crossed 120 mesh sieves, with lactose, ethyl cellulose, magnesium stearate and Pulvis Talci mix homogeneously, direct compression of full-powder.
The release experiment is with embodiment 1, and the result is as follows:
Time (hour) cumulative release degree %
1 23.4％
2 36.9％
4 60.3％
8 87.6％
Embodiment 4 carbazochrome sodium sulfonate mixed type matrix tablets
Prescription:
Carbazochrome sodium sulfonate 30g
HPMC?K4M 25g
Glyceryl monostearate 15g
Lactose 90g
Magnesium stearate 1.5g
Pulvis Talci 1.5g
Preparation technology:
Card taking network sulphur sodium raw materials medicine, pulverizing is also crossed 120 mesh sieves, with lactose, HPMC K4M, glyceryl monostearate, magnesium stearate and Pulvis Talci mix homogeneously, direct compression of full-powder.
The release experiment is with embodiment 1, and the result is as follows:
Time (hour) cumulative release degree %
1 30.2％
2 42.6％
4 70.0％
8 98.5％
Embodiment 5
Prescription:
Carbazochrome sodium sulfonate 30g
Carbomer 20g
Pregelatinized Starch 50g
Lactose 80g
Magnesium stearate 1.8g
Pulvis Talci 1.8g
Preparation technology adopts direct compression of full-powder.
The release experiment is with embodiment 1, and the result is as follows:
Time (hour) cumulative release degree %
1 20.7％
2 37.3％
4 68.4％
8 101.3％
Claims (6)
1, a kind of sustained-release matrix tablets that contains the active pharmaceutical ingredient carbazochrome sodium sulfonate is characterized in that being made up of crude drug, framework material, diluent, binding agent and lubricant, and its prescription is composed as follows by weight percentage:
Carbazochrome sodium sulfonate 5%～85%
Framework material 10%～90%
Diluent 0～80%
Binding agent is an amount of
Lubricant is an amount of
2, carbazochrome sodium sulfonate slow-released tablet according to claim 1, its preparation method is as follows:
The preparation method of carbazochrome sodium sulfonate slow-released tablet of the present invention comprises: will be formed by direct compression of full-powder behind the supplementary material mixing; Or make tablet with lubricant mixing repress after supplementary material made granule; Or get part material medicine and auxiliary materials and mixing earlier, and make immediate release section, surplus stock medicine, framework material and diluent mixing as slow-released part, are pressed into the bilayer tablet that has release layer and slow release layer simultaneously; Method of granulating comprises dry method, wet method, fusing or fusion etc.
3, carbazochrome sodium sulfonate slow-released tablet according to claim 1 is characterized in that:
Framework material can be a cellulose derivative, as ethyl cellulose, methylcellulose, hyprolose, hypromellose, carboxymethyl cellulose etc.; Can be biodegradation material, comprise materials such as waxiness, fatty acid and esters thereof, as stearic acid, glyceryl monostearate, Brazil wax, octadecanol, hexadecanol, Tridocosanoin etc.; Can be acrylic polymer, as carbomer, acrylic resin etc.; Can also be that other has the material that delays the drug release effect, as sodium alginate, guar gum, pectin, modified starch, chitosan, polyvinyl alcohol, polyethylene, polypropylene, polysiloxanes etc.; Various framework materials also can mix use and make mixed matrix type slow releasing tablet.
Diluent comprises one or more mixing wherein such as microcrystalline Cellulose, each kind of starch, lactose, sucrose, mannitol, preferred pregelatinized Starch and lactose; Diluent also comprises the material of scalable drug release rate such as porogen etc., as fructose, sorbitol, sodium chloride, Polyethylene Glycol, polyvidone, surfactant etc.
Binding agent comprises the mixed solution, hypromellose, polyvidone, methylcellulose, ethyl cellulose of water or alcohol, water and alcohol etc.;
Lubricant is magnesium stearate or calcium, Pulvis Talci, micropowder silica gel, sodium lauryl sulphate or magnesium etc.
4, carbazochrome sodium sulfonate slow-released tablet according to claim 1 is characterized in that medicine can continue to discharge more than 5 hours, and effective blood drug concentration can be kept 12 hours.
5, carbazochrome sodium sulfonate slow-released tablet according to claim 1 can be made the cut sheet, so better divided dose.
6, carbazochrome sodium sulfonate slow-released tablet according to claim 1 has following drug release characteristics in water, pH6.8 and 7.2 buffer (according to Chinese Pharmacopoeia method preparation) or mimic physiological environment (in the simulated gastric fluid 1～2 hour, change simulated intestinal fluid again over to):
Time (hour) cumulative release amount %
1 ≤40％
2 ≤60％
4 ≤90％
8 ≥70％
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2006101662067A CN100571700C (en) | 2006-12-20 | 2006-12-20 | Carbazochrome sodium sulfonate slow-released tablet and preparation method thereof |
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|---|---|---|---|
| CNB2006101662067A CN100571700C (en) | 2006-12-20 | 2006-12-20 | Carbazochrome sodium sulfonate slow-released tablet and preparation method thereof |
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| CN1985808A true CN1985808A (en) | 2007-06-27 |
| CN100571700C CN100571700C (en) | 2009-12-23 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101129358B (en) * | 2007-07-11 | 2010-04-21 | 山东省医药工业研究所 | Moguisteine sustained-release tablet and method of preparing the same |
| CN101797235A (en) * | 2010-03-19 | 2010-08-11 | 西南大学 | Carbazochrome sodium sulfonate oral disintegrating tablets and preparation method thereof |
| CN102973535A (en) * | 2012-12-13 | 2013-03-20 | 广西方略药业集团有限公司 | Probucol controlled-release tablet for treatment of hypercholesteremia and production method thereof |
| CN103145603A (en) * | 2013-03-15 | 2013-06-12 | 湖北济生医药有限公司 | Carbazochrome sodium sulfonate compound and medical composition thereof |
| CN115813870A (en) * | 2022-12-21 | 2023-03-21 | 江苏吴中医药集团有限公司 | Carbazochrome sodium sulfonate tablets and preparation method thereof |
| CN115813870B (en) * | 2022-12-21 | 2024-05-10 | 江苏吴中医药集团有限公司 | Carbazochrome sodium sulfonate tablet and preparation method thereof |
-
2006
- 2006-12-20 CN CNB2006101662067A patent/CN100571700C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101129358B (en) * | 2007-07-11 | 2010-04-21 | 山东省医药工业研究所 | Moguisteine sustained-release tablet and method of preparing the same |
| CN101797235A (en) * | 2010-03-19 | 2010-08-11 | 西南大学 | Carbazochrome sodium sulfonate oral disintegrating tablets and preparation method thereof |
| CN101797235B (en) * | 2010-03-19 | 2012-05-09 | 西南大学 | Carbazochrome sodium sulfonate oral disintegrating tablets and preparation method thereof |
| CN102973535A (en) * | 2012-12-13 | 2013-03-20 | 广西方略药业集团有限公司 | Probucol controlled-release tablet for treatment of hypercholesteremia and production method thereof |
| CN103145603A (en) * | 2013-03-15 | 2013-06-12 | 湖北济生医药有限公司 | Carbazochrome sodium sulfonate compound and medical composition thereof |
| CN103145603B (en) * | 2013-03-15 | 2014-12-17 | 湖北济生医药有限公司 | Carbazochrome sodium sulfonate compound and medical composition thereof |
| CN115813870A (en) * | 2022-12-21 | 2023-03-21 | 江苏吴中医药集团有限公司 | Carbazochrome sodium sulfonate tablets and preparation method thereof |
| CN115813870B (en) * | 2022-12-21 | 2024-05-10 | 江苏吴中医药集团有限公司 | Carbazochrome sodium sulfonate tablet and preparation method thereof |
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| Publication number | Publication date |
|---|---|
| CN100571700C (en) | 2009-12-23 |
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Address after: Xinluo Avenue high tech Zone of Ji'nan City, Shandong province 250101 No. 989 Shandong Academy of Pharmaceutical Sciences Room 401 Patentee after: Medicine Industry Inst., Shandong Prov. Address before: 250100 Shandong Pharmaceutical Industry Research Institute, 52 Da Bei Road, Shandong, Ji'nan Patentee before: Medicine Industry Inst., Shandong Prov. |
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