CN1807440A - Sodium menadiol diphosphate ester and its pharmaceutical formulation - Google Patents
Sodium menadiol diphosphate ester and its pharmaceutical formulation Download PDFInfo
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- CN1807440A CN1807440A CN 200610002615 CN200610002615A CN1807440A CN 1807440 A CN1807440 A CN 1807440A CN 200610002615 CN200610002615 CN 200610002615 CN 200610002615 A CN200610002615 A CN 200610002615A CN 1807440 A CN1807440 A CN 1807440A
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- dispersible tablet
- menadiol
- sodium diphosphate
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Abstract
The invention relates to a compound of a-haphthyl hydroquinone diphosphonate natrium and its medicinal preparation which used to treat hypoprothrom-binemia caused by various reasons, especially referring to dispersed piece and Process for the manufacture of a-haphthyl hydroquinone diphosphonate natrium. Selecting thinner contains calcium hydrogen phosphate and disintegration agent contains microcrystalline cellulose and crosslinking sodium carboxymethylcellulose as findings of dispersed piece, during the process, the granules are uniform, the liquidity is fine, the dispersed piece of a-haphthyl hydroquinone diphosphonate natrium can disperse quickly and disintegrate in the water, improving availability of pharmaceutical biology. The technology is simple and stable; the dispersed pieces are accord with the requirement of clinical application.
Description
Technical field
The present invention relates to the Menadiol sodium diphosphate hexahydrate compound and the pharmaceutical preparation thereof of the Hypoprothrombinemia that a kind of treatment causes because of a variety of causes, especially relate to Menadiol sodium diphosphate hexahydrate dispersible tablet and preparation method thereof.
Background technology
Vitamin K is the essential material of the synthetic thrombogen (factor II) of liver, and it is synthetic to go back participation factors VII, factors IX and factor X.The K that is deficient in vitamin can cause above-mentioned thrombin dyssynthesis, influences coagulation process and causes bleeding.
Menadiol sodium diphosphate hexahydrate is a vitamin K
3The synthetic product, change vitamin k4 (vitamin K in vivo into
3), can be used for suffering from biliary tract or the hepatic diseases relevant with the courage function, part patient suffers from functional gastrointestinal disorder relevant with vitamin K deficiency or serious septicemia.
Summary of the invention
The invention provides a kind of vitamin K class therapeutic active substance menadiol sodium diphosphate and its drug preparation, especially Menadiol sodium diphosphate hexahydrate dispersible tablet and preparation method thereof.
For achieving the above object, technical scheme of the present invention is;
A kind of Menadiol sodium diphosphate hexahydrate of Formula I structure:
Formula I
Its molecular formula is C
11H
8Na
4O
8P
26H
2O, molecular weight is 530.17, chemical name is: the 2-methyl isophthalic acid, two (dihydrogen phosphoric acid ester) the tetra-na salt hexahydrates of 4-naphthalene quinhydrones, active medicine for vitamin K, can be used for treating the Hypoprothrombinemia that causes because of a variety of causes, be used to suffer from biliary tract or the hepatic diseases relevant with the courage function clinically, part patient suffers from functional gastrointestinal disorder relevant with vitamin K deficiency or serious septicemia.
The present invention also provides a kind of pharmaceutical composition, and it comprises the Menadiol sodium diphosphate hexahydrate of the above-mentioned Formula I structure for the treatment of significant quantity and pharmaceutically conventional auxiliary material.
Especially, the invention provides a kind of Menadiol sodium diphosphate hexahydrate dispersible tablet, comprise Menadiol sodium diphosphate hexahydrate, thinner, disintegrating agent, tackiness agent and lubricant, it is characterized in that described thinner comprises secondary calcium phosphate, described disintegrating agent comprises Microcrystalline Cellulose and croscarmellose sodium.
Wherein, above-mentioned described dispersible tablet of the present invention, wherein said thinner also can further comprise micropowder silica gel.
Above-mentioned described dispersible tablet, tackiness agent wherein is used to the usefulness of granulating, and can be tackiness agent pharmaceutically commonly used, for example can be in polyvidone, Vltra tears, starch slurry or the dextrin one or more; Wherein, preferred adhesive is a polyvidone.
Above-mentioned described dispersible tablet, lubricant wherein can be lubricant pharmaceutically commonly used, for example is in stearic acid, Magnesium Stearate, polyoxyethylene glycol, micropowder silica gel or the talcum powder one or more; Preferred emollient of the present invention is a Magnesium Stearate.
If desired, the above-mentioned described dispersible tablet of the present invention also can comprise correctives or effervescent.Correctives for example is N.F,USP MANNITOL, Xylitol, stevioside, lactose, fructose, sucrose, protein sugar, maltose alcohol, glycyrrhizin, Sodium Cyclamate, gelatin, aspartame, banana flavour, flavoring pineapple essence, vanillin food grade,1000.000000ine mesh, fragrant citrus essence, flavoring orange essence, peppermint essence, ginseng essence, strawberry flavour, Citric Acid, citric acid etc., can use use also capable of being combined separately.Effervescent for example is the mixture of oxysuccinic acid, citric acid or Citric Acid and sodium bicarbonate or yellow soda ash.
As the present invention's one preferred embodiment, shown dispersible tablet, wherein calculate by weight, 10 parts of Menadiol sodium diphosphate hexahydrates, 70 parts of secondary calcium phosphates, 140 parts of Microcrystalline Celluloses, 24 parts of croscarmellose sodiums, 10 parts of micropowder silica gels, 2.6 parts of Magnesium Stearates, the tackiness agent polyvidone of granulation usefulness is an amount of.
Another purpose of the present invention has provided a kind of preparation method of above-mentioned described Menadiol sodium diphosphate hexahydrate dispersible tablet, and it comprises Menadiol sodium diphosphate hexahydrate and auxiliary materials and mixing, granulates with tackiness agent, and particle adds the lubricant mixing, carries out compressing tablet.
As preferred implementation, the above-mentioned described method for preparing the Menadiol sodium diphosphate hexahydrate dispersible tablet comprises
(1) with Menadiol sodium diphosphate hexahydrate and micropowder silica gel and croscarmellose sodium mixing partly;
(2) with Microcrystalline Cellulose and secondary calcium phosphate and step (1) gained material mixing;
(3) step (2) gained material is granulated with tackiness agent;
(4) step (3) gained particle is added lubricant and remaining croscarmellose sodium, mixing carries out compressing tablet.
Wherein, described tackiness agent can be the 5% polyvidone aqueous solution, and prepared wet granular can be 50～60 ℃ of forced air dryings.
Menadiol sodium diphosphate hexahydrate dispersible tablet of the present invention and preparation method thereof, by selecting for use secondary calcium phosphate, micropowder silica gel as thinner, the uniform particles that makes; Select for use Microcrystalline Cellulose and croscarmellose sodium as disintegrating agent, the dispersible tablet that makes has good disintegration, thereby obtains good preparation effect, has overcome the deficiency that Menadiol sodium diphosphate hexahydrate exists.In addition, the present invention adopts unique prescription to form, and Menadiol sodium diphosphate hexahydrate is made dispersible tablet, following characteristics are arranged: (1) can disperse rapidly in 3 minutes in water, and disintegration forms uniform suspension, disperse strong attitude good, disintegration time is short, and the medicine stripping is rapid; Absorb soon the bioavailability height; (2) easy administration.It is various that dispersible tablet is taken mode, can swallow, chew to contain and suck or with taking after the water-dispersion, especially is fit to the elderly, paralytic or the patient of the difficulty of swallowing takes; (3) production technique of dispersible tablet is identical with conventional tablet, need not particular requirement, and technology is simple, and the technology cost is low, and the dispersible tablet of production is stable, has good preparation effect.
Concrete aforesaid way
Further specify and explain the present invention by the following examples, but this should not be interpreted as limiting the scope of the invention.
Embodiment 1:
Menadiol sodium diphosphate hexahydrate 10g, micropowder silica gel 10g, Microcrystalline Cellulose 140g, secondary calcium phosphate 70g, croscarmellose sodium 24g, the 5% polyvidone aqueous solution is an amount of, Magnesium Stearate 2.6g.Recipe quantity Menadiol sodium diphosphate hexahydrate, micropowder silica gel are mixed with the 12g croscarmellose sodium, cross 100 mesh sieves; Microcrystalline Cellulose, secondary calcium phosphate mix with the equivalent incremental method with above-mentioned fine powder after crossing 100 mesh sieves respectively, with the 5% polyvidone aqueous solution is tackiness agent system softwood, 24 mesh sieves are granulated, wet granular 55-60 ℃ forced air drying 3 hours, the whole grain of dried particle 22 mesh sieves, add 12g croscarmellose sodium and Magnesium Stearate and mix, measure content, it is heavy to calculate slice.
Specification: 5mg: with 7mm drift compressing tablet
Specification: 10mg: with 9mm drift compressing tablet
With the tablet inspection that makes, packing promptly.
Embodiment 2:
Menadiol sodium diphosphate hexahydrate 10g, micropowder silica gel 10g, Microcrystalline Cellulose 140g, secondary calcium phosphate 70g, croscarmellose sodium 30g, the 5% polyvidone aqueous solution is an amount of, Magnesium Stearate 2.6g.According to embodiment 1 described same procedure, make dispersible tablet.
Embodiment 3:
3a) with lactose 40g, low-substituted hydroxypropyl cellulose 30g, sodium starch glycolate 30g, corresponding secondary calcium phosphate and croscarmellose sodium in the alternative embodiment 1.According to described same procedure, prepare dispersible tablet.
3b) with lactose 40g, low-substituted hydroxypropyl cellulose 40g, corresponding secondary calcium phosphate and micropowder silica gel make dispersible tablet by described same procedure in the alternative embodiment 2.
Measure disintegration and particle situation, compare, the results are shown in Table 1.The result shows: the prescription of embodiment 3a, 3b is formed, and particle is looser, and mobile bad, institute's tablet agent disintegration time was about 4～4.5 minutes.Embodiment 1 and 2 prescription are formed, and particle is more even, and better mobile, institute's tablet agent disintegration time was about 1～1.5 minute.
This shows, Menadiol sodium diphosphate hexahydrate of the present invention is by selecting the thinner that comprises secondary calcium phosphate for use, comprises the auxiliary material of the disintegrating agent etc. of Microcrystalline Cellulose, croscarmellose sodium as dispersible tablet, in the preparation process, uniform particles, good fluidity, the Menadiol sodium diphosphate hexahydrate dispersible tablet of making can disperse disintegration rapidly in 2 minutes in water, form uniform suspension, disperse strong attitude good, disintegration time is short, and the medicine stripping is rapid; Absorb soon the bioavailability height.
Table 1 test-results
Claims (10)
1, a kind of Menadiol sodium diphosphate hexahydrate of Formula I structure:
Formula I
2, a kind of pharmaceutical composition, it comprises the Menadiol sodium diphosphate hexahydrate of the described Formula I structure of the claim 1 for the treatment of significant quantity and pharmaceutically conventional auxiliary material.
3, a kind of Menadiol sodium diphosphate hexahydrate dispersible tablet, comprise Menadiol sodium diphosphate hexahydrate, thinner, disintegrating agent, tackiness agent and lubricant, it is characterized in that described thinner contains secondary calcium phosphate, described disintegrating agent comprises Microcrystalline Cellulose and croscarmellose sodium.
4, dispersible tablet according to claim 3, wherein said thinner also comprises micropowder silica gel.
5, according to the described dispersible tablet of claim 3-4, wherein said tackiness agent can be one or more in polyvidone, Vltra tears, starch slurry or the dextrin; Preferred adhesive is a polyvidone.
6, according to the described dispersible tablet of claim 3-5, wherein said lubricant can be one or more in stearic acid, Magnesium Stearate, polyoxyethylene glycol, micropowder silica gel or the talcum powder; Preferred emollient is a Magnesium Stearate.
7, according to the described dispersible tablet of claim 3-6, wherein also can comprise correctives or effervescent.
8, dispersible tablet according to claim 3 wherein calculates 10 parts of Menadiol sodium diphosphate hexahydrates by weight, 70 parts of secondary calcium phosphates, 140 parts of Microcrystalline Celluloses, 24 parts of croscarmellose sodiums, 10 parts of micropowder silica gels, 2.6 parts of Magnesium Stearates, the tackiness agent polyvidone of granulation usefulness is an amount of.
9, the preparation method of the described dispersible tablet of claim 3-8 comprises Menadiol sodium diphosphate hexahydrate and auxiliary materials and mixing, granulates with tackiness agent, and particle adds the lubricant mixing, carries out compressing tablet.
10, method according to claim 9, wherein:
(1) with Menadiol sodium diphosphate hexahydrate and micropowder silica gel and croscarmellose sodium mixing partly;
(2) with Microcrystalline Cellulose and secondary calcium phosphate and step (1) gained material mixing;
(3) step (2) gained material is granulated with tackiness agent;
(4) step (3) gained particle is added lubricant and remaining croscarmellose sodium, mixing carries out compressing tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100026153A CN100497353C (en) | 2006-01-26 | 2006-01-26 | Sodium menadiol diphosphate ester and its pharmaceutical formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100026153A CN100497353C (en) | 2006-01-26 | 2006-01-26 | Sodium menadiol diphosphate ester and its pharmaceutical formulation |
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| Publication Number | Publication Date |
|---|---|
| CN1807440A true CN1807440A (en) | 2006-07-26 |
| CN100497353C CN100497353C (en) | 2009-06-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100026153A Expired - Fee Related CN100497353C (en) | 2006-01-26 | 2006-01-26 | Sodium menadiol diphosphate ester and its pharmaceutical formulation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106580898A (en) * | 2016-12-15 | 2017-04-26 | 扬子江药业集团有限公司 | Breviscapine dispersible tablet and preparing method thereof |
-
2006
- 2006-01-26 CN CNB2006100026153A patent/CN100497353C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106580898A (en) * | 2016-12-15 | 2017-04-26 | 扬子江药业集团有限公司 | Breviscapine dispersible tablet and preparing method thereof |
| CN106580898B (en) * | 2016-12-15 | 2019-09-20 | 扬子江药业集团有限公司 | A kind of erigeron breviscapus dispersion tablet and preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100497353C (en) | 2009-06-10 |
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Application publication date: 20060726 Assignee: Wuxi Fortune Pharmaceutical Co., Ltd. Assignor: Zhou Zhuohe Contract record no.: 2010440000416 Denomination of invention: Sodium menadiol diphosphate ester and its pharmaceutical formulation Granted publication date: 20090610 License type: Exclusive License Record date: 20100416 |
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Granted publication date: 20090610 Termination date: 20120126 |