CN103494792B - Compound phloroglucinol freeze-dried orally-disintegrating tablet and preparation method - Google Patents
Compound phloroglucinol freeze-dried orally-disintegrating tablet and preparation method Download PDFInfo
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- CN103494792B CN103494792B CN201310377383.XA CN201310377383A CN103494792B CN 103494792 B CN103494792 B CN 103494792B CN 201310377383 A CN201310377383 A CN 201310377383A CN 103494792 B CN103494792 B CN 103494792B
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Abstract
The invention provides a compound phloroglucinol freeze-dried orally-disintegrating tablet and a preparation method. The compound phloroglucinol freeze-dried orally-disintegrating tablet contains phloroglucinol and trimethoxyphloroglucinol as active components, has disintegration time within 10s and is not broken easily. The compound phloroglucinol freeze-dried orally-disintegrating tablet (also known as a compound phloroglucinol freeze-dried tablet) comprises main drugs and auxiliary materials, and the auxiliary materials comprise four raw materials. The compound phloroglucinol freeze-dried orally-disintegrating tablet is prepared by a freeze drying technology. The compound phloroglucinol freeze-dried orally-disintegrating tablet has high porosity, just melts in the mouth, has a good taste and no gravel feel, contains a small amount of the auxiliary materials, has small tablet weight and volume, is not broken easily, and can be taken without water and produce effects fast. The compound phloroglucinol freeze-dried orally-disintegrating tablet can disintegrate under the tongue in 10s, can prevent degradation by stomach acid and first-pass hepatic metabolism, can obviously reduce side effects and can reduce stimulation effects on the alimentary canal.
Description
Technical field
The invention belongs to pharmaceutical arts, particularly a kind of compound recipe phloroglucinol freeze-dry orally disintegrating tablet and preparation method.
Background technology:
Brown algae polyphenols is the natural product of a class formation uniqueness, and its basic structural unit is phloroglucinol.Phloroglucinol has another name called root bark former times phenol, phloroglucinol, and phloroglucinol has more than 40 year in France and the application of other European countries, has also had nearly 8 years in China.Its spasmolysis is rapid, Be very effective and do not have the feature of toxic and side effects to be approved by people widely.A large amount of clinical test results has affirmed fully the using value of phloroglucinol in fields such as department of obstetrics and gynecology, urology department, liver-divisions of gastroenterology.
Phloroglucinol/TRIMETHYL PHLOROGLUCINOL belongs to a kind of novel spasmolytic antalgica, and it directly acts on gastrointestinal tract and urogenital tract smooth muscle, is the pure flat sliding flesh spasmolytic of the non-atropine of close muscular non-Semen Papaveris bases.Compared with other smooth muscle spasmolysis medicine, the feature of phloroglucinol/TRIMETHYL PHLOROGLUCINOL does not have cholinolytic effect, while releasing smooth muscle spasm, can not produce the side effect of a series of cholinolytic sample.Phloroglucinol and TRIMETHYL PHLOROGLUCINOL all can not cause the symptoms such as hypotension, increased heart rate, arrhythmia, do not affect cardiovascular function.Animal pharmacological test shows, and it only acts on spasm smooth muscle, minimum on normal smooth muscle impact.Subacute toxicity and long term toxicity test display, phloroglucinol and TRIMETHYL PHLOROGLUCINOL do not have harmful effect to the both macro and micro histology of growth of animal, vitals, blood and biochemical indicator: special toxicity test research shows, phloroglucinol, 1,3,5-trimethoxy benzene does not have teratogenesis, mutagenesis (carcinogenic) property.
After phloroglucinol, TRIMETHYL PHLOROGLUCINOL administration, the highest at liver, kidney and small intestine's distributed density, cerebral tissue is minimum, a small amount of drug residue is only had in body after 48 hours, the metabolism in vivo of this medicine is mainly through the glucose coupling of liver, through urinary tract and defecate, medicine is all discharged with the form of glucose conjugates through urinary tract excretion.
This phloroglucinol compound preparation is applicable to the acute painful muscle spasms that digestive system and biliary tract function of patients obstacle cause; Acute spastic urethra, bladder, renal colic; Gynecological's spasmic pain.
Phloroglucinol alleviate puerpera's spontaneous labor painful in be with a wide range of applications.Result of study shows, phloroglucinol injection significantly can shorten delivery time, accelerates dilatation of cervix, shortens delivery time, thus alleviates puerpera's misery.
On current domestic and international market, the dosage form of existing phloroglucinol has injection and freeze-dry orally disintegrating tablet.Its injection has domestic manufacturer and produces; Phloroglucinol freeze-dry orally disintegrating tablet (having another name called phloroglucinol oral freeze-dried slices) is domestic does not still have launch; Phloroglucinol oral freeze-dried slices is produced at French Laboratoire L.Lafon, commodity are called Phloroglucinol (Spasfon-Lyoc), but the weight of its sheet is (about 700 milli gram/piece) greatly, volume large (diameter is about 16 millimeters), easy dry linting, frangible, production cost is high.The adjuvant of lyophilizing orally disintegrating tablet is macrodex, mannitol.Its technique is freeze drying process.Result of extraction is poor.France LaboratoireL.Lafon produces the oral coated tablet Spasfon-comprime (rose) of compound recipe phloroglucinol in addition, active component is phloroglucinol, TRIMETHYL PHLOROGLUCINOL, product goes on the market, and this sheet obviously absorbs slow than oral cavity disintegration tablet, onset is slow.
The final technical purpose of oral disintegrated preparation is that disintegrate is rapid, and good mouthfeel makes patient be easy to accept, improves the compliance of patient.According to research, the time of staying of general foreign body in mouth, people just had the trained reflex chewing foreign body more than 15 seconds.Disintegration time was a goldstandard within 15 seconds.Inventor of the present invention finds under study for action, the phloroglucinol oral freeze-dried slices of France's listing, and because adjuvant addition is too much, disintegration time has exceeded 30 seconds, and the frangible easy dry linting of the lyophilizing sheet of this listing.
Current nothing adopts lyophilization to obtain the pertinent literature report of compound recipe phloroglucinol freeze-dry orally disintegrating tablet both at home and abroad.
Summary of the invention:
The present invention is directed to Problems existing in the above-mentioned technology of existing product, existing compound recipe phloroglucinol normal packet garment piece is modified into compound recipe phloroglucinol freeze-dry orally disintegrating tablet, the advantage of novel formulation is: can take in anhydrous conditions and quick acting, i.e. disintegratable release within Sublingual 10 second, then buccal absorption is passed through, by mucosa before stomach, enter superior vena cava, the drug effect of such absorption is fast, bioavailability is high, gastric acid degradation and first pass effect of hepar can be avoided simultaneously, obviously can reduce side effect, reduce advantages such as alimentary canal mucous membrane zest are little.
Compound recipe phloroglucinol freeze-dry orally disintegrating tablet prepared by the present invention, the porosity of slice, thin piece is high, has the sensation of just melt in the mouth, and mouthfeel is good, supplementary product consumption is few, and the heavy volume of sheet is little, non-friable.
Present inventor, by research to this lyophilizing tablet preparation technique, finds to add a certain amount of low polyxylose alcohol in binding agent sodium alginate, can greatly shorten disintegrate drug release time, makes this lyophilizing sheet can in i.e. disintegratable release in Sublingual 10 seconds.
Present inventor is through further investigation, have been surprisingly found that in the preparation technology of this oral cavity disintegration tablet, add a small amount of zein, significantly can increase the toughness of lyophilizing sheet, make it not easily fragmentation not easily dry linting, solve the problem of the ubiquitous frangible easy dry linting of conventional freeze dry tablet.
The object of the present invention is to provide a kind of freeze-dry orally disintegrating tablet of phloroglucinol compound preparation; It comprises active component phloroglucinol and TRIMETHYL PHLOROGLUCINOL, and major auxiliary burden sodium alginate, low polyxylose alcohol and zein.
Described freeze-dry orally disintegrating tablet is i.e. disintegratable release in Sublingual 10 seconds, is more preferably less than or equal to 8 seconds; Be more preferably less than or equal to 6 seconds; And/or the hardness of described freeze-dry orally disintegrating tablet is less than or equal to 1%, is more preferably less than or equal to 0.6%; And/or described compositions unit dose is less than 700mg, is preferably less than or equal to 600mg, is more preferably less than or equal to 500mg, be less than or equal to 400mg, be less than or equal to 300mg, most preferably 270-290mg.。
The freeze-dry orally disintegrating tablet of described phloroglucinol compound preparation, by: in dihydrate, the phloroglucinol of 80 weight portions; The TRIMETHYL PHLOROGLUCINOL of 80 weight portions; The sodium alginate of 60-80 weight portion; The low polyxylose alcohol of 30 weight portions; The zein of 5 weight portions; Form with the stevioside of 1 weight portion.
Preferably described weight portion unit is mg.
In one preferred embodiment, the freeze-dry orally disintegrating tablet of described phloroglucinol compound preparation, the component of every sheet consists of:
A principal agent: 80 milligrams of phloroglucinol (by dihydrate), 80 milligrams of TRIMETHYL PHLOROGLUCINOLs.
B adjuvant: 60-80 milligram sodium alginate, 30 milligrams of low polyxylose alcohols, 5 milligrams of zeins, 1 milligram of stevioside.
The preparation method that present invention also offers this freeze-dry orally disintegrating tablet comprises the following steps:
Phloroglucinol, TRIMETHYL PHLOROGLUCINOL are dissolved in aqueous solution, add sodium alginate, oligomeric xylose, stevioside dissolving, make solution A; Zein is added in the ethanol water of appropriate 75% and dissolve, make solution A; By solution A and solution B mixing, and add appropriate water dilution, be fully mixed; Dividing is filled in the mould of suitable volumes, and through sharp freezing, putting into freeze dryer evacuation, and sublime up into material bone dry, press seal, packaging, is lyophilizing sheet.
Detailed description of the invention:
In further detail the present invention is described below by way of embodiments and comparative examples.
Prepare compound recipe phloroglucinol freeze-dry orally disintegrating tablet according to the composition shown in table 1 and quantity thereof, its concrete grammar is as follows:
Phloroglucinol, TRIMETHYL PHLOROGLUCINOL are dissolved in aqueous solution, add sodium alginate, oligomeric xylose, stevioside dissolving, make solution A; Zein is added in the ethanol water of appropriate 75% and dissolve, make solution A; By solution A and solution B mixing, and add appropriate water dilution, be fully mixed; Dividing is filled in the mould of suitable volumes, and through sharp freezing, putting into freeze dryer evacuation, and sublime up into material bone dry, press seal, packaging, is lyophilizing sheet.
Table 1
For a better understanding of the present invention, by the mouthfeel experiment of compound recipe phloroglucinol freeze-dry orally disintegrating tablet of preparation, disintegration time mensuration, friability mensuration, advantage of the present invention is described below:
1, disintegration:
Get preparation prepared by experimental example 1-3 and first comparative example 1-3, compound recipe Spaston orally disintegrating tablets prepared by second comparative example 1-3, measure by the following method: get 1, each sample, put in the test tube being added with 2m1 water (37 DEG C ± 1 DEG C) respectively, timing is started with stopwatch, until the complete disintegrate of tablet by No. 2 sieves, suitable quantity of water can be added if desired and get screen cloth express developed.According to said method each sample respectively checks 10.
2, mouthfeel experiment:
Compound recipe phloroglucinol freeze-dry orally disintegrating tablet respectively prepared by Example 1-3, after 10 healthy volunteer's mouths are tasted, this preparation good mouthfeel: be placed in after on tongue that disintegrate is rapid, sugariness is moderate, without bitter, without husky walk about sense.
3, friability test:
10 lyophilizing sheets are put into the CS-II type friability instrument of Tianjin Guo Ming Pharmaceuticals Ltd, 25 revs/min, after rotating 100 turns, measuring the percentage ratio of loss of weight is friability, be no more than 1% be certified products.
The disintegration time of the oral cavity disintegration tablet prepared with the formula of the first and second comparative example 1-3 according to embodiment 1-3, mouthfeel test, friability test result (tablet prepared of each identical embodiment and comparative example all measures 10, gets its meansigma methods) as shown in table 2.
Table 2 each routine average disintegration time limit, mouthfeel experiment, friability result
| Meansigma methods (n=5) | Disintegration | Mouthfeel is tested | Friability result |
| Embodiment 1 | 5 seconds | Just melt in the mouth, mouthfeel is good | 0.6%, non-friable not dry linting |
| First comparative example 1 | 5 seconds | Just melt in the mouth, mouthfeel is good | 8%, there is the easy dry linting of fracture |
| Second comparative example 1 | 30 seconds | Chew foreign body sensation | 6%, there is the easy dry linting of fracture |
| Embodiment 2 | 5 seconds | Just melt in the mouth, mouthfeel is good | 0.5%, non-friable not dry linting |
| First comparative example 2 | 6 seconds | Just melt in the mouth, mouthfeel is good | 7%, there is fracture |
| Second comparative example 2 | 35 seconds | Chew foreign body sensation | 5%, there is fracture to split |
| Embodiment 3 | 6 seconds. | Just melt in the mouth, mouthfeel is good | 0.4%, non-friable not dry linting |
| First comparative example 3 | 7 seconds | Just melt in the mouth, mouthfeel is good | 6%, there is fracture |
| Second comparative example 3 | 36 seconds | Chew foreign body sensation | 5%, there is fracture to split |
As can be seen from Table 2, add the embodiment 1-3 first comparative example 1-3 after low polyxylose alcohol to compare the second comparative example 1-3 disintegration time not adding oligomeric xylose and greatly shorten within 10 seconds.
As can be seen from Table 2, the friability adding the lyophilizing sheet of the embodiment 1-3 after a small amount of zein is all less than 1%, belongs to acceptability limit.And the friability not adding the first comparative example 1-3 of a small amount of zein and the lyophilizing sheet of second comparative example 1-3 is all greater than 5%, belong to defective scope, the effect that lyophilizing sheet adds the anti-friability of zein is amazing.
The heavy volume of sheet of the compound recipe phloroglucinol freeze-dry orally disintegrating tablet prepared in embodiments of the invention also reduces greatly, sheet is heavily only 280mg, compare the heavy 700mg of sheet that French Laboratoire L.Lafon on market produces phloroglucinol oral freeze-dried slices, the heavy volume-diminished of sheet is over half, and adjuvant materials are few.
Compound recipe phloroglucinol freeze-dry orally disintegrating tablet of the present invention is by sublingual administration, and common compound recipe phloroglucinol coated tablet Spasfon-comprime (rose) that French Lafon can be avoided to produce also exists medicine by the risk of stomach acids destroy.
It should be noted, can revise arbitrarily for various details of the present invention, but certainly, these amendments will fall within protection scope of the present invention.
Claims (1)
1. a freeze-dry orally disintegrating tablet for compound recipe phloroglucinol, is characterized in that described freeze-dry orally disintegrating tablet is by dihydrate, the phloroglucinol of 80 weight portions; The TRIMETHYL PHLOROGLUCINOL of 80 weight portions; The sodium alginate of 60-80 weight portion; The low polyxylose alcohol of 30 weight portions; The zein of 5 weight portions; Form with the stevioside of 1 weight portion.
2. freeze-dry orally disintegrating tablet according to claim 1, is characterized in that the i.e. disintegratable release in Sublingual 10 seconds of described freeze-dry orally disintegrating tablet; The friability of described freeze-dry orally disintegrating tablet is less than or equal to 1%; Described compositions unit dose is less than 700mg.
3. freeze-dry orally disintegrating tablet according to claim 1 and 2, is characterized in that described freeze-dry orally disintegrating tablet is by dihydrate, the phloroglucinol of 80 weight portions; The TRIMETHYL PHLOROGLUCINOL of 80 weight portions; The sodium alginate of 60 weight portions; The low polyxylose alcohol of 30 weight portions; The zein of 5 weight portions; Form with the stevioside of 1 weight portion; Freeze-dry orally disintegrating tablet i.e. disintegratable release in 5 seconds in Sublingual; The friability of freeze-dry orally disintegrating tablet is 0.6%.
4. freeze-dry orally disintegrating tablet according to claim 1 and 2, is characterized in that described freeze-dry orally disintegrating tablet is by dihydrate, the phloroglucinol of 80 weight portions; The TRIMETHYL PHLOROGLUCINOL of 80 weight portions; The sodium alginate of 70 weight portions; The low polyxylose alcohol of 30 weight portions; The zein of 5 weight portions; Form with the stevioside of 1 weight portion; Freeze-dry orally disintegrating tablet i.e. disintegratable release in 5 seconds in Sublingual; The friability of freeze-dry orally disintegrating tablet is 0.5%.
5. freeze-dry orally disintegrating tablet according to claim 1 and 2, is characterized in that described freeze-dry orally disintegrating tablet is by dihydrate, the phloroglucinol of 80 weight portions; The TRIMETHYL PHLOROGLUCINOL of 80 weight portions; The sodium alginate of 80 weight portions; The low polyxylose alcohol of 30 weight portions; The zein of 5 weight portions; Form with the stevioside of 1 weight portion; Freeze-dry orally disintegrating tablet i.e. disintegratable release in 6 seconds in Sublingual; The friability of freeze-dry orally disintegrating tablet is 0.4%.
6. according to the freeze-dry orally disintegrating tablet described in claim 1, it is characterized in that, described freeze-dry orally disintegrating tablet, the component of every sheet consists of:
A principal agent: in dihydrate, 80 milligrams of phloroglucinol; 80 milligrams of TRIMETHYL PHLOROGLUCINOLs;
B adjuvant: 60-80 milligram sodium alginate; 30 milligrams of low polyxylose alcohols; 5 milligrams of zeins; 1 milligram of stevioside.
7. according to the freeze-dry orally disintegrating tablet described in claim 1, it is characterized in that the preparation method of described freeze-dry orally disintegrating tablet comprises the following steps:
Phloroglucinol, TRIMETHYL PHLOROGLUCINOL are dissolved in aqueous solution, add sodium alginate, low polyxylose alcohol, stevioside dissolving, make solution A; Zein is added in the ethanol water of appropriate 75% and dissolve, make solution B; By solution A and solution B mixing, and add appropriate water dilution, be fully mixed; Dividing is filled in the mould of suitable volumes, and through sharp freezing, putting into freeze dryer evacuation, and sublime up into material bone dry, press seal, packaging, is freeze-dry orally disintegrating tablet.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3107183A1 (en) * | 2020-02-19 | 2021-08-20 | Jean-Paul AMSELLEM | Composition for the treatment of vertigo |
| JP7323451B2 (en) | 2017-03-08 | 2023-08-08 | シンリックス ファーマ、エルエルシー | Pharmaceutical preparations of phloroglucinol and trimethylphloroglucinol |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109157520B (en) * | 2018-09-07 | 2021-04-02 | 苏州科技城医院 | Tadalafil tablet and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101209249A (en) * | 2006-12-26 | 2008-07-02 | 海南高升医药科技开发有限公司 | Spaston orally disintegrating tablets and preparation thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101209249A (en) * | 2006-12-26 | 2008-07-02 | 海南高升医药科技开发有限公司 | Spaston orally disintegrating tablets and preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| 间苯三酚口服冻干制剂影响因素的考察;陈丹等;《中国医院药学杂志》;20130715(第16期);第1-4页 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7323451B2 (en) | 2017-03-08 | 2023-08-08 | シンリックス ファーマ、エルエルシー | Pharmaceutical preparations of phloroglucinol and trimethylphloroglucinol |
| FR3107183A1 (en) * | 2020-02-19 | 2021-08-20 | Jean-Paul AMSELLEM | Composition for the treatment of vertigo |
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