CN1413583A - Low dose diclofenac sodium lozenge and its preparation method - Google Patents
Low dose diclofenac sodium lozenge and its preparation method Download PDFInfo
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Abstract
A low-dosage lozenge of diclofenac sodium contains diclofenac sodium, sugar powder, mannitol, maltose dextrin, menthol, polyvidone K30 solution and magnesium stearate, and is prepared by solvent dispersing method or particle coating method. It can be used for treating oral inflammation.
Description
Technical field
The present invention relates to a kind of low dose diclofenac sodium lozenge and preparation method thereof.
Background technology
Diclofenac sodium is potent non_steroidal anti_inflammatory drug, and its easing pain and diminishing inflammation act as 2-2.5 times of indomethacin, and the 26-50 of aspirin doubly.Be used for the treatment of rheumatism, rheumatoid arthritis, scapulohumeral periarthritis, tenosynovitis clinically, injure the pain that causes inflammation such as operation outward, wait the heating that causes that good efficacy is also arranged flu.Though the diclofenac sodium lighter non-steroidal analgesic that is a kind of toxic and side effects, but also occurred many untoward reaction in clinical practice, main adverse reactions has clinically: gastrointestinal reaction such as upper abdomen discomfort, feel sick, vomiting, occur gastrointestinal hemorrhage, dizziness, erythra, granulocytopenia etc. when serious.Now clear and definite, the generation of most of untoward reaction is relevant with using dosage.At present, the clinical using method of diclofenac sodium is the 25mg tablet, a 1-2 sheet, three times on the one; The 75mg injection, one time one, 1-2 time on the one.That is to say that the consumption per day of diclofenac sodium is at least 75mg.
The department of stomatology and department of otorhinolaryngology all have more exodontia and pars oralis pharyngis surgical patient every day, and work and life that inflammation that operation back local damage causes and pain have a strong impact on patient give local anesthetic, and the analgesic effect persistent period is short, and does not have the antiinflammatory effect; Give morphine class analgesic when pain is serious and also have same defective, in addition, narcotic is being restricted aspect the clinical use; Clinical use nonsteroidal anti-inflammatory analgetic causes easily that with oral or injection system administration digestive tract reaction and use are inconvenient and difficult by doctor and patient's acceptance.Therefore, a kind of like this medicament of demand, it not only has analgesic activity but also antiinflammatory action is arranged, and under the prerequisite that does not lessen the curative effect, it is minimum that untoward reaction is dropped to.At present diclofenac sodium is developed many kinds of preparations according to different agents areas, comprises that ordinary preparation such as eye drop are used for the treatment of eyes conjunctivitis, keratitis, scleritis and prevent disease such as postcataract myosis; Suppository is used for the treatment of the pain relieving of renal colic; Mucilage rectally treatment renal colic, biliary colic, sustained-release and controlled release preparation such as slow releasing tablet, slow-release micro-pill blood drug level are held time and long are reduced the medication number of times, and external preparation such as gel, liniment, solution and ointment local concentration height, rapid-action, Transdermal absorption have well been avoided again gastrointestinal is stimulated and first-pass effect.However, also do not have at present a kind of be suitable for oral disease such as oral ulcer or have a toothache or perform the operation as tooth pulling surgery or tonsil resection postoperative analgesic diclofenac sodium rapid-action, effect is lasting but the little preparation of side effect.The inventor has been developed into a kind of buccal tablet dosage form of diclofenac sodium of low dosage administration.
Summary of the invention
The present invention has just provided the lasting also low dose diclofenac sodium buccal tablet of the significantly reduced oral administration of side effect of a kind of antalgic and inflammation relieving time, can in exodontia and pars oralis pharyngis operation back inflammation and treatment of conditions such as pain, oral ulcer, acute pharyngitis and periodontitis, continue performance pain relieving and antiinflammatory action, and reduce the untoward reaction of diclofenac sodium systemic administration.
The content of diclofenac sodium is the 1-5mg/ sheet in the buccal tablet of the present invention, is preferably the 2mg/ sheet.Buccal tablet is when oral administration, there are substantial connection in local drug concentration and salivation amount, salivation is divided into static salivation and dynamic salivation, represent with static saliva total flow rate and dynamic saliva total flow rate respectively, in general, the no more than 0.6g/min of the static secretory volume of saliva is that 1 calculating is 0.6ml/min by proportion.Dynamically secretory volume (acid stimulates or the Chewing gum nurse) is not higher than 3g/min, approximately 3ml/min.The excretory effect of certain saliva stimulating is arranged during the buccal buccal tablet.Calculate according to dynamic saliva amount, the buccal time is estimated 20-30min, and the salivation amount is approximately 90ml.At this moment the concentration of the diclofenac sodium in the saliva is 22 μ g/ml, far above the maximum drug level of the blood of oral administration.After every specification of 10 once oral diclofenac sodiums of healthy Chinese subjects was the 75mg tablet, pharmacokinetic parameter showed, T
MaxMaximum=1.78 ± 0.31 hours; C
MaxMaximum=4.12 μ g/ml, C
MaxMinimum=1.04 μ g/ml, meansigma methods is 1.9 ± 0.9 μ g/m1.Oral mucosa is better to drug permeability, and operation on oral cavity has wound surface, and medicine can directly contact with wound surface, thus can obtain better therapeutic effect, and topical is more rapid than the other administration route onset.
Buccal tablet of the present invention contains following component:
Diclofenac sodium, diluent, adhesive solution, lubricant, wherein diclofenac sodium: diluent: adhesive solution: the ratio between the lubricant is 0.1-1: 90-98: 20-30: 0.5-1.5; Diluent of the present invention is Icing Sugar, mannitol, maltose, and wherein the ratio between Icing Sugar, mannitol, the maltose is 1: 0.5-1.25: 0.25-1.25; Adhesive is the 3-5% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution, Gonak; Be preferably 4% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution; Lubricant is a magnesium stearate.
Best prescription is diclofenac sodium 1 weight portion, Icing Sugar 150 weight portions, mannitol 150 weight portions, maltodextrin 100 weight portions, 4% 30 POVIDONE K 30 BP/USP in the aforementioned proportion of the present invention
3050% alcoholic solution, 42 weight portions, magnesium stearate 1 weight portion.
Can also add correctives and coloring agent in the buccal tablet prescription of the present invention, wherein correctives is a Mentholum, and the 0.3-0.7% that it accounts for buccal tablet weight is preferably 0.5%; Coloring agent is a lemon yellow, and the 0.1-0.3% that it accounts for buccal tablet weight is preferably 0.25%.
In the above-mentioned prescription of buccal tablet of the present invention, diclofenac sodium is an active component, and Icing Sugar, mannitol, maltodextrin are diluent; 30 POVIDONE K 30 BP/USP
30Alcoholic solution be binding agent; Magnesium stearate is a lubricant.
Because diclofenac sodium is a water soluble drug, and dosage is little in the present invention's prescription, belong to small dose drug, need add suitable diluent for this reason, common diluent comprises lactose, mannitol, maltodextrin and Icing Sugar, they are to the outward appearance of tablet, granule compressibility and tablet hardness, disintegration time, mouthfeel is all influential, find that through test lactose contains the slag sense as diluent port, so select Icing Sugar for use, mannitol and maltodextrin are as the diluent in the preparation of the present invention, they are all water soluble adjuvant, can in the oral cavity, dissolve fully when sucking, can improve the mouthfeel of tablet, Icing Sugar and maltodextrin have compressibility preferably, maltodextrin can play certain adhesive effect again, helps improving the hardness of tablet, makes buccal tablet keep long drug release time at the oral cavity medicine position, adjust disintegration time, can prolong drug effect in the part.
Also used binding agent in the preparation of the present invention, common binding agent comprises the 30 POVIDONE K 30 BP/USP of gelatin solution, simple syrup, variable concentrations
30Alcoholic solution and CARPOLMER
974pThe inventor selects 10% gelatin solution, 60% simple syrup solution, 3%, 4%, 5% 30 POVIDONE K 30 BP/USP respectively for use
3050% alcoholic solution, 1%CARPOLMER
974pMake binding agent and granulate, observe the influence of binding agent tablet appearance, disintegration time, technological feasibility.The result is as shown in table 1, and 10% gelatin solution is granulated and stickingly is difficult for sieving, and tabletting is unilateral YIN macules; 60% simple syrup is granulated sticking, sticks with paste screen cloth, and granule is inhomogeneous, and unilateral have a bulk dark color spots, and disintegration time is longer; 3% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution is granulated easily, and uniform particles is complete, and tabletting is unilateral bright and clean, and disintegration time is 10min, and the time of sucking is 17min; 4% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution is granulated easily, and uniform particles is complete, and tabletting is unilateral bright and clean, and disintegration time is 13min, and the time of sucking is 20min; 5% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution is granulated easily, and uniform particles is complete, and tabletting is unilateral bright and clean, and disintegration time is 15min, and the time of sucking is 23min; 1%CARPOLMER
974pSolution system soft material is agglomerating, is difficult for being uniformly dispersed, and has jelly to glue screen cloth during granulation, and it is hard to make granule, and compressibility is good, but unilateral not bright and clean, considers to require short disintegration time, so select 4% 30 POVIDONE K 30 BP/USP for use
3050% alcoholic solution is as the binding agent of preparation of the present invention.
Table 1. binding agent is to the influence of tablet appearance, disintegration time, technological feasibility
| Binding agent | Tablet appearance | Disintegration time | The technology operability |
| 10% gelatin solution | YIN macules is arranged | ??20min | Granule is sticking, is difficult for sieving |
| 60% simple syrup | Dark color spots | ??19min | Granule is sticking, is difficult for sieving |
| 3% 30 POVIDONE K 30 BP/USP 3050% alcoholic solution | Unilateral bright and clean | ??10min | Granulate easily, uniform particles is complete |
| 4% 30 POVIDONE K 30 BP/USP 3050% alcoholic solution | Unilateral bright and clean | ??13min | Granulate easily, uniform particles is complete |
| 5% 30 POVIDONE K 30 BP/USP 3050% alcoholic solution | Unilateral bright and clean | ??15min | Granulate easily, uniform particles is complete |
| ??1％CARPOMER 974p | YIN macules is arranged | ??23min | Soft material sticks into group, is difficult for being uniformly dispersed, and has jelly to glue screen cloth during granulation |
When adding correctives in the present invention's prescription, preferably make correctives with Mentholum, can be so that buccal tablet mouthfeel of the present invention be more clearly good to eat.In order to determine the appropriate level of Mentholum, the inventor prepares blank buccal tablet, calls up the volunteer and tries clothes, and fill in opinionaire, is tried 30 people, and test result is as shown in table 2, and 0.5% Mentholum mouthfeel is better, is 0.5% so select the Mentholum consumption for use.
The consumption of table 2. Mentholum is to the influence of mouthfeel
| The consumption of Mentholum | Mouthfeel |
| ????0.25％ | No cooling effect |
| ????0.5％ | Cool taste |
| ????0.75％ | Cool taste, slightly fiber crops |
When the present invention added coloring agent, the inventor had not only paid attention to the purpose that makes tablet attractive in appearance, and [" 2000 editions diclofenac sodiums of Chinese pharmacopoeia adopt ultraviolet spectrophotometry to have considered to disturb the mensuration of buccal tablet active component diclofenac sodium.Therefore the inventor also screens coloring agent, and the result is as shown in table 3, the tablet color even unanimity that 0.25% lemon yellow makes, and the 284nm uv absorption is little, is the coloring agent of buccal tablet so select lemon yellow.
Table 3 coloring agent is to the influence of tablet appearance and diclofenac sodium determination
| Coloring agent | Tablet appearance | Coloring agent A 248/ diclofenac sodium A 248(％) |
| Light green (0.025%) | Color is dark green, and color and luster is inhomogeneous | ???1.3％ |
| Tender leaf green (0.025%) | Color is emerald green, the color and luster unanimity | ???1.0％ |
| Lemon yellow (0.025%) | Light yellow uniformity | ???0.3％ |
In addition, lubricant selects for use magnesium stearate to increase particulate flowability, and tablet weight variation is less during tabletting, and is unilateral bright and clean.
Behind above-mentioned selected respectively suitable adjuvant, the inventor has carried out screening to find out best consumption by test to the different amounts combination of these adjuvants again.The inventor presses the different proportionings of active component and adjuvant, and it is as shown in table 4 to draft 6 pharmaceutical formulations.After making buccal tablet, check outward appearance, mouthfeel, disintegration time, percentage composition, uniformity of dosage units, friability, tablet weight variation, the result is as shown in table 5.
Several pharmaceutical formulations of table 4. are formed
| Component | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 |
| Diclofenac sodium (mg) | ??2000 | ??2000 | ??2000 | ??2000 | ????2000 | ????2000 |
| Icing Sugar (g) | ??700 | ??300 | ??400 | ??200 | ????300 | ????400 |
| Mannitol (g) | ??200 | ??400 | ??200 | ????300 | ????200 | |
| Maltodextrin (g) | ??100 | ??300 | ??400 | ????200 | ????200 | |
| Mentholum (g) | ??2.00 | ??4.00 | ??6.00 | ??3.00 | ????4.00 | ????5.00 |
| Lemon yellow (g) | ??0.20 | ??0.25 | ??0.30 | ??0.20 | ????0.25 | ????0.30 |
| 3% 30 POVIDONE K 30 BP/USP 3050 | ??88 |
| % alcoholic solution (g) | ||||||
| 4% 30 POVIDONE K 30 BP/USP 3050 % alcoholic solution (g) | ??85 | |||||
| 5% 30 POVIDONE K 30 BP/USP 3050 % alcoholic solution (g) | ??91 | |||||
| ??1％CARPOMER 974pSolution (g) | ????40 | |||||
| 1% Gonak (g) | ????73 | ????80 | ??- | |||
| Magnesium stearate (%) | ????1.5％ | ????1％ | ????0.5％ | ??1％ | ??1％ | ??1％ |
The difference of table 5 observation index
| Inspection item | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 |
| Outward appearance | YIN macules | YIN macules | YIN macules | Faint yellow | Light yellow | Yellow |
| Mouthfeel | Sweet taste | Clearly | Slightly numb | Clearly | Clearly | Clearly |
| Disintegrate | ??20 | ??19 | ??18 | ??10 | ??13 | ??15 |
| Percentage composition | ??98.5％ | ??98.2％ | ??102.6％ | ??101.4％ | ??100.8％ | ??101.5％ |
| Uniformity of dosage units | Qualified (6.3) | Qualified (5.8) | Qualified (6.1) | Qualified (5.1) | Qualified (4.9) | Qualified (5.3) |
| Friability | ??0.1％ | ??0.2％ | ??0.3％ | ??0.2％ | ??0.2％ | ??0.2％ |
| Tablet weight variation | ??4.8％ | ??5.1％ | ??4.9％ | ??4.0％ | ??4.0％ | ??4.3％ |
By table 4 and 5 as can be seen, outward appearance, the mouthfeel of prescription 5 are better, and preparation technology is workable, disintegration time 13 minutes, the time of sucking is 20 minutes, unilateral no obvious YIN macules, sheet is heavily stable during tabletting, tablet weight variation less (the RSD value is 4.1%), it is accurate to make tablet content, tablet has uniformity of dosage units preferably, and the requirement all up to specification of each index is so select prescription 5 prescriptions as preparation of the present invention.
Buccal tablet of the present invention can adopt that any routine fashion makes in this area, as solvent dispersion method, granule coating method.
If adopt the solvent dispersion method, exactly Icing Sugar, mannitol, maltodextrin are crossed 100 mesh sieves, mix homogeneously is dissolved in diclofenac sodium, flavoring agent Mentholum and contains 4% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution in, be dispersed in the diluent, make soft material, granulate, oven dry, dried granule adds the magnesium stearate lubricant, mixing, arrangement, tabletting.Every contains diclofenac sodium 2mg.
If adopt the granule coating method, preparation process comprises crosses 100 mesh sieves with Icing Sugar, mannitol, maltodextrin, and mix homogeneously is made binding agent with Gonak, one-step palletizing becomes blank granule, diclofenac sodium, correctives Mentholum is dissolved in contain 4% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution in, evenly send forth on blank granule, make the signal granule, dried granule adds magnesium stearate, mixing, granulate, tabletting, every contains diclofenac sodium 2mg.
Just because of the present invention has adopted above-mentioned pharmaceutical formulation, so it can play more effective pain relieving and antiinflammatory action that continues for inflammation and the pain that causes with oral ulcer after the minor operation of oral cavity clinically, and oral cavity partial there is not obvious irritation, although CN1203792A discloses a kind of compound pividone iodine sucking tablet, wherein contain diclofenac sodium, but diclofenac sodium only is as a kind of composition in the coating solution, though also contain the 2mg diclofenac sodium in every, but this buccal tablet is compared obviously low with the diclofenac sodium buccal tablet that the present invention contains same dose on the time of the persistency of analgesic activity and antiinflammatory action, in order to reach same effect, must increase and take number of times, also increase a day use amount thereupon, be unfavorable for the reduction of side effect.
Below further describe the present invention by comparative experimental example and preparation embodiment, but be not limited to this.
The preparation of embodiment 1. diclofenac sodium buccal tablets
A. fill a prescription:
Diclofenac sodium 2.0g
Icing Sugar 300g
Mannitol 300g
Maltodextrin 200g
Mentholum 4.0g
4% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution solution 85g
Magnesium stearate 1%
Make 1000
B. preparation method: Icing Sugar, mannitol, maltodextrin are crossed 100 sieves, and mix homogeneously is dissolved in 4% 30 POVIDONE K 30 BP/USP with diclofenac sodium, flavoring agent Mentholum
30In the 50%Z alcoholic solution solution adhesive, be dispersed in the diluent, make soft material, 18 mesh sieves are granulated, 50 ℃ of oven dry, and dried granule adds the magnesium stearate lubricant, mixing, 16 mesh sieve granulate, tabletting.Every contains diclofenac sodium 2mg.
The preparation of embodiment 2. diclofenac sodium buccal tablets
A. fill a prescription:
Diclofenac sodium 20g
Icing Sugar 3000g
Mannitol 3000g
Maltodextrin 2000g
Mentholum 40g
4% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution 2000ml
Gonak 2900ml
Magnesium stearate 1%
Make 10000
B. preparation method: Icing Sugar, mannitol, maltodextrin are crossed 100 sieves, and mix homogeneously is made binding agent with Gonak, and one-step palletizing becomes blank granule, and diclofenac sodium, correctives Mentholum are dissolved in 4% 30 POVIDONE K 30 BP/USP
30In 50% alcoholic solution, evenly send forth on blank granule, make granule, dried granule adds magnesium stearate, mixing, and 16 mesh sieve granulate, tabletting, every contains diclofenac sodium 2mg.
Test example 1. diclofenac sodium buccal tablets and compound povidone iodine buccal tablet analgesic activity are relatively
A. material: acetic acid; Diclofenac sodium
Animal: secondary Kunming kind white mice, male and female half and half, body weight 19-21g.
The solution preparation:
0.6% acetic acid preparation: get pure acetic acid 0.6ml in the 100ml volumetric flask, add the injection normal saline, be settled to scale.
Oral diclofenac sodium preparation: get 150.2mg diclofenac sodium crude drug in the 100ml volumetric flask, add the injection normal saline, be settled to scale, be the solution of concentration 1.5mg/ml.
The test preparation of diclofenac sodium buccal tablet solution:
Get diclofenac sodium buccal tablet a slice, place the 50ml beaker respectively, add normal saline 10ml, shake 2min gently with 10 times/min, tablet is taken out another beaker of adding, operation is carried out 8 times altogether with above-mentioned.
The test preparation of compound povidone iodine buccal tablet solution:
Get compound povidone iodine buccal tablet a slice, place the 50ml beaker respectively, add normal saline 10ml, shake 2min gently with 10 times/min, tablet is taken out another beaker of adding, operation is carried out 8 times altogether with above-mentioned.
B. method: get white mice, be divided into 18 groups at random, 10 every group.Negative control group: every decimal intraperitoneal injection of saline 0.20ml, the acetic acid 0.20ml of pneumoretroperitoneum injection 0.6% in 10 minutes, timing is observed in the 10min and is turned round the body number of times.
Positive controls (oral diclofenac sodium): every oral concentration of white mice is 1.5mg/ml diclofenac sodium solution 0.20ml, the acetic acid 0.20ml of 60min pneumoretroperitoneum injection 0.6%, and timing is observed in the 10min and is turned round the body number of times.
The diclofenac sodium buccal tablet solution group of test:
Every diclofenac sodium buccal tablet solution 0.20ml that the mouse peritoneal injection prepares, the acetic acid 0.20ml of 10min pneumoretroperitoneum injection 0.6%, timing is observed in the 10min and is turned round the body number of times.The povidone iodine buccal tablet solution group of test:
Every povidone iodine buccal tablet solution 0.20ml that the mouse peritoneal injection prepares, the acetic acid 0.20ml of 10min pneumoretroperitoneum injection 0.6%, timing is observed in the 10min and is turned round the body number of times.
C. result: the result is as shown in table 6, and the solution in 8 beakers of diclofenac sodium all has significant analgesia role, and compound povidone iodine has only the 1st, 2 solution in the beaker to have analgesic activity, illustrates that the diclofenac sodium buccal tablet has longer analgesic activity.Table 6. diclofenac sodium and compound povidone iodine Dichlorodiphenyl Acetate cause the comparison of mouse writhing reaction (number of times) influence
| The beaker serial number | The diclofenac sodium buccal tablet | The compound povidone iodine buccal tablet |
| ????1 | ????6.2±3.3 ** | ????6.4±3.0 ** |
| ????2 | ????6.4±2.4 ** | ????5.9±3.2 ** |
| ????3 | ????7.1±3.2 ** | ????32.1±9.2 |
| ????4 | ????7.7±4.9 ** | ????31.5±7.8 |
| ????5 | ????7.6±4.8 ** | ????34.7±6.6 |
| ????6 | ????8.8±4.3 ** | ????31±7.3 |
| ????7 | ????14.7±4.0 ** | ????32.3±7.5 |
| ????8 | ????17.5±7.6 ** | ????35.9±4.5 |
| Negative control (normal saline) | ????33.6±7.4 |
| Positive control (diclofenac sodium solution) | ????4.1±5.2 ** |
Annotate:
*P＜0.01,
*Compare with negative control group p＜0.05.
Test example 2. diclofenac sodium buccal tablets and compound povidone iodine buccal tablet are to the comparison of capillary permeability influence (antiinflammatory) effect.
A. material: centrifuge, D1-4000B refrigerated centrifuger; Spectrophotometer (UV-9100).Acetic acid; Diclofenac sodium
Animal: secondary Kunming kind white mice, male and female half and half, body weight 19-21g.
The solution preparation:
0.8% acetic acid preparation: get pure acetic acid 0.80ml in the 100ml volumetric flask, add the injection normal saline, be settled to scale.
Oral diclofenac sodium preparation: get 150.2mg diclofenac sodium crude drug in the 100ml volumetric flask, add the injection normal saline, be settled to scale, be the solution of concentration 1.5mg/ml.
The test preparation of diclofenac sodium buccal tablet solution:
Get diclofenac sodium buccal tablet a slice, place the 50ml beaker respectively, add normal saline 10ml, shake 2min gently with 10 times/min, tablet is taken out another beaker of adding, operation is carried out 8 times altogether with above-mentioned.
The test preparation of compound povidone iodine buccal tablet solution:
Get compound povidone iodine buccal tablet a slice, place the 50ml beaker respectively, add normal saline 10ml, shake 2min gently with 10 times/min, tablet is taken out another beaker of adding, operation is carried out 8 times altogether with above-mentioned.
The preparation of azovan blue solution: get 500.4mg in azovan blue 100ml volumetric flask, add the injection normal saline, be settled to scale, promptly concentration is the solution of 0.5% (w/v).
B. method: get 180 of white mice, be divided into 18 groups at random, 10 every group.Negative control group: every mouse mainline 0.5% azovan blue solution, injected dose is 0.10ml/10g, immediately the acetic acid 0.20ml of lumbar injection 0.8% and normal saline 0.20ml, intraperitoneal injection of saline 0.20ml again behind the 10min, put to death mice behind the 10min, draw the 6.0ml normal saline, at twice (3ml, 3ml) wash the abdominal cavity, soft abdominal part is drawn peritoneal fluid, centrifugal (3000rpm, 5min), measure absorption value in 590nm.
Positive controls (oral diclofenac sodium): every white mice gavages 1.5mg/ml diclofenac sodium solution 0.20ml, every mouse mainline 0.5% azovan blue solution behind the 60min, injected dose is 0.10ml/10g, the acetic acid 0.20ml of lumbar injection 0.8% and normal saline 0.20ml immediately, intraperitoneal injection of saline 0.20ml again after 10 minutes, put to death mice after 10 minutes, draw the 6.0ml normal saline, (3ml 3ml) washes the abdominal cavity, soft abdominal part at twice, draw peritoneal fluid, it is centrifugal that (3000rpm 5min), measures absorption value in 590nm.
The diclofenac sodium buccal tablet solution group of test: every mouse mainline 0.5% azovan blue solution, injected dose is 0.10ml/10g, the acetic acid 0.20ml of lumbar injection 0.8% and the test for preparing immediately is with diclofenac sodium buccal tablet solution 0.20ml, intraperitoneal injection of saline 0.20ml again behind the 10min, put to death mice after 10 minutes, draw the 6.0ml normal saline, (3ml at twice, 3m1) wash the abdominal cavity, soft abdominal part is drawn peritoneal fluid, centrifugal (3000rpm, 5min), measure absorption value in 590nm.
The povidone iodine buccal tablet solution group of test:
Every mouse mainline 0.5% azovan blue solution, injected dose is 0.10ml/10g, immediately the acetic acid 0.20ml of lumbar injection 0.8% and the test for preparing povidone iodine buccal tablet solution 0.20ml, intraperitoneal injection of saline 0.20ml again behind the 10min, put to death mice behind the 10min, draw the 6.0ml normal saline, at twice (3ml, 3ml) wash the abdominal cavity, soft abdominal part is drawn peritoneal fluid, centrifugal (3000rpm, 5 minutes), measure absorption value in 590nm.
C. result: as shown in table 7, solution in 8 beakers of diclofenac sodium all has the obvious suppression effect, and compound povidone iodine has only the 1st, 2 solution in the beaker that capillary permeability is had the obvious suppression effect, illustrates that the diclofenac sodium buccal tablet has the longer antiinflammatory action time.
Table 7. diclofenac sodium and compound povidone iodine are to the comparison of capillary permeability influence
| The beaker serial number | The diclofenac sodium buccal tablet | The compound povidone iodine buccal tablet |
| 1 | ????0.135±0.037 ** | ????0.127±0.021 ** |
| 2 | ????0.134±0.041 ** | ????0.132±0.034 ** |
| 3 | ????0.136±0.039 ** | ????0.183±0.040 |
| 4 | ????0.135±0.030 ** | ????0.193±0.035 |
| 5 | ????0.152±0.046 ** | ????0.188±0.045 |
| 6 | ????0.139±0.037 ** | ????0.195±0.040 |
| 7 | ????0.139±0.036 ** | ????0.198±0.036 |
| 8 | ????0.142±0.033 ** | ????0.201±0.041 |
| Negative control (normal saline) | ????0.1?95±0.039 | |
| Positive control (diclofenac sodium solution) | ????0.112±0.029 ** |
Annotate:
*P＜0.01,
*Compare with negative control group p＜0.05.
Claims (11)
1. low dose diclofenac sodium lozenge is characterized by and contains diclofenac sodium, diluent, adhesive solution, lubricant, wherein diclofenac sodium: diluent: adhesive solution: the ratio of lubricant is 0.1-1: 90-98: 20-30: 0.5-1.5.
2. according to the described low dose diclofenac sodium lozenge of claim 1, its diluent is Icing Sugar, mannitol, maltose, and wherein the ratio between Icing Sugar, mannitol, the maltose is 1: 0.5-1.25: 0.25-1.25; Adhesive is the 3-5% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution, Gonak; Lubricant is a magnesium stearate.
3. according to the described low dose diclofenac sodium lozenge of claim 2, wherein adhesive is 4% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution.
4. according to the arbitrary described low dose diclofenac sodium lozenge among the claim 1-3, its prescription is dichlorophen sodium 1 weight portion, Icing Sugar 150 weight portions, mannitol 150 weight portions, maltodextrin 100 weight portions, 4% 30 POVIDONE K 30 BP/USP
3050% alcoholic solution, 40 weight portions, magnesium stearate 1 weight portion.
5. according to the described low dose diclofenac sodium lozenge of claim 1, wherein can also contain correctives, coloring agent.
6. according to the described low dose diclofenac sodium lozenge of claim 5, wherein correctives is a Mentholum, and it accounts for the 0.3-0.7% of buccal tablet weight; Coloring agent is a lemon yellow, and it accounts for the 0.1-0.3% of buccal tablet weight.
7. according to the described low dose diclofenac sodium lozenge of claim 6, wherein Mentholum is 0.5% of a buccal tablet weight; Lemon yellow is 0.25% of a buccal tablet weight.
8. according to the arbitrary described low dose diclofenac sodium buccal tablet among the claim 1-7, wherein every contains diclofenac sodium buccal tablet 1-5mg.
9. according to the described low dose diclofenac sodium buccal tablet of claim 8, wherein every contains diclofenac sodium buccal tablet 2mg.
10. as the preparation method of low dose diclofenac sodium buccal tablet as described in the claim 1-9, it comprises the following steps: Icing Sugar, mannitol, maltodextrin are crossed 100 sieves, and mix homogeneously is dissolved in diclofenac sodium, flavoring agent Mentholum and contains 4% 30 POVIDONE K 30 BP/USP
30Ethanol 50% solution adhesive in, be dispersed in the diluent, make soft material, granulate, oven dry, dried granule adds the magnesium stearate lubricant, mixing, arrangement, tabletting makes.
11. each method of system as low dose diclofenac sodium buccal tablet as described in the claim 1-9, it comprises the following steps: Icing Sugar, mannitol, maltodextrin are crossed 100 sieves, mix homogeneously, make binding agent with Gonak, one-step palletizing becomes blank granule, diclofenac sodium, correctives Mentholum is dissolved in contain 4% 30 POVIDONE K 30 BP/USP
30Ethanol 50% solution in, evenly send forth on blank granule, make granule, dried granule adds magnesium stearate, mixing, granulate, tabletting makes.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01136082 CN1204883C (en) | 2001-10-08 | 2001-10-08 | Low dose diclofenac sodium lozenge and its preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01136082 CN1204883C (en) | 2001-10-08 | 2001-10-08 | Low dose diclofenac sodium lozenge and its preparation method |
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| CN1413583A true CN1413583A (en) | 2003-04-30 |
| CN1204883C CN1204883C (en) | 2005-06-08 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823167A (en) * | 2017-12-15 | 2018-03-23 | 湖南千金协力药业有限公司 | A kind of silybin meglumine tablets and preparation method thereof |
-
2001
- 2001-10-08 CN CN 01136082 patent/CN1204883C/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107823167A (en) * | 2017-12-15 | 2018-03-23 | 湖南千金协力药业有限公司 | A kind of silybin meglumine tablets and preparation method thereof |
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| Publication number | Publication date |
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| CN1204883C (en) | 2005-06-08 |
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