CN106110328A - A kind of utilize calcium phosphate precipitation auxiliary improve ibuprofen method of dissolubility in water - Google Patents
A kind of utilize calcium phosphate precipitation auxiliary improve ibuprofen method of dissolubility in water Download PDFInfo
- Publication number
- CN106110328A CN106110328A CN201610502441.0A CN201610502441A CN106110328A CN 106110328 A CN106110328 A CN 106110328A CN 201610502441 A CN201610502441 A CN 201610502441A CN 106110328 A CN106110328 A CN 106110328A
- Authority
- CN
- China
- Prior art keywords
- ibuprofen
- dissolubility
- polyvinyl alcohol
- calcium phosphate
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
Abstract
A kind of utilize calcium phosphate precipitation auxiliary improve ibuprofen method of dissolubility in water, belong to technical field of medicine.The most first L glutamic acid, disodium hydrogen phosphate and sodium hydroxide are added in deionized water, add carbamide, calcium nitrate and trisodium citrate until completely dissolved, after being completely dissolved, solution is added to the reaction vessel being placed with polyvinyl alcohol and ibuprofen, it is warming up to 100 DEG C and is incubated furnace cooling after 24 hours, then the supernatant solution obtained after calcium phosphate precipitation and centrifugal separation is the aqueous solution of ibuprofen high-dissolvability.The chemical reagent that this method is used is cheap, technique is simple, it is easy to industrialized production.In preparation-obtained aqueous solution, ibuprofen dissolubility is high, reaches 4.43 ~ 8.80 milligrams every milliliter.
Description
Technical field
A kind of utilize calcium phosphate precipitation auxiliary improve ibuprofen method of dissolubility in water, belong to drug preparation technique neck
Territory.
Background technology
Ibuprofen is widely used in antipyretic, analgesia and the field such as antiinflammatory, and ibuprofen bitter in the mouth, half-life be short, in aqueous solution
Dissolubility little (about 0.07 milligram every milliliter).The low medication effect that greatly limit ibuprofen of dissolubility in water, bag
Include drug absorption speed, bioavailability and play the speed etc. of effect, to maintain the treatment concentration of ibuprofen to be accomplished by frequently
Take medicine, so can increase the gastrointestinal burden of patient, also greatly limit the application of ibuprofen.The dosage form of development at present
Having suspension, slow releasing tablet and slow releasing capsule etc., ibuprofen dissolubility in water then can develop injection type after improving,
While improving the medication effect of ibuprofen, it is also applied for swallowing the crowds such as the child of inconvenience, old man and severely injured patient,
The method that visible exploration improves ibuprofen dissolubility in aqueous is the most necessary.The method improving ibuprofen dissolubility has addition
The cosolvent such as sodium hydroxide or arginine, and the correlational study utilizing calcium phosphate precipitation auxiliary to improve ibuprofen dissolubility is reported non-
The fewest.
Summary of the invention
It is an object of the invention to provide a kind of utilize calcium phosphate precipitation auxiliary improve ibuprofen method of dissolubility in water,
Will be put in the solution of calcium ions and phosphate anion by ibuprofen, in water-heat process calcium phosphate precipitate, ibuprofen
Melt and be gradually dissolved in aqueous solution.For achieving the above object, technical scheme step is as follows:
(1) first Pidolidone, disodium hydrogen phosphate and sodium hydroxide are added in deionized water, make Pidolidone, disodium hydrogen phosphate
It is respectively 0.091,0.024 and 0.039 mole every liter with the concentration of sodium hydroxide, adds carbamide, calcium nitrate until completely dissolved
And trisodium citrate, make the concentration of carbamide, calcium nitrate and trisodium citrate be 0.056 ~ 0.222,0.026 and 0.013 mole every
Rising, add in the reaction vessel containing polyvinyl alcohol and ibuprofen after being completely dissolved, polyvinyl alcohol selects molecular weight to be 105000
The addition of polyvinyl alcohol 124, ibuprofen and polyvinyl alcohol and the mol ratio of calcium nitrate are respectively 1.65:1 and 1.22 × 10-3:
1；
(2) furnace cooling after the reaction solution that step (1) is prepared being warming up to 100 DEG C and being incubated 24 hours, then calcium phosphate is sunk
The supernatant solution obtained after the centrifugation of shallow lake is the aqueous solution of ibuprofen high-dissolvability.
The beneficial effects of the present invention is:
1. the chemical reagent that this method is used is cheap, technique is simple, it is easy to industrialized production；
2. the chemical reagent biocompatibility used by this method is high, and the calcium phosphate chemistry precipitation that reaction generates is easily by routine point
Separate from means；
3. the preparation-obtained pH value of water solution of this method is neutral or slant acidity, is in the pH value range of Human Tolerance；
4. in the preparation-obtained aqueous solution of this method, ibuprofen dissolubility is high, reaches 4.43 ~ 8.80 milligrams every milliliter.
Detailed description of the invention
Embodiment 1
(1) first Pidolidone, disodium hydrogen phosphate and sodium hydroxide are added in 90 ml deionized water, make Pidolidone, phosphoric acid
The concentration of disodium hydrogen and sodium hydroxide is respectively 0.091,0.024 and 0.039 mole every liter, add until completely dissolved carbamide,
Calcium nitrate and trisodium citrate, make the concentration of carbamide, calcium nitrate and trisodium citrate be 0.056,0.026 and 0.013 mole every
Rising, add in the reaction vessel being placed with polyvinyl alcohol and ibuprofen after being completely dissolved, polyvinyl alcohol selects molecular weight to be 105000
Polyvinyl alcohol 124, the addition of ibuprofen and polyvinyl alcohol and the mol ratio of calcium nitrate are respectively 1.65:1 and 1.22 × 10-3:1；
(2) furnace cooling after the reaction solution that step (1) is prepared being warming up to 100 DEG C and being incubated 24 hours, then calcium phosphate is sunk
The supernatant solution obtained after the centrifugation of shallow lake is the aqueous solution of ibuprofen high-dissolvability.
After tested, the pH value of the aqueous solution of ibuprofen high-dissolvability is 6.38, and ibuprofen dissolubility in aqueous reaches
To 4.43 milligrams every milliliter.
Embodiment 2
(1) first Pidolidone, disodium hydrogen phosphate and sodium hydroxide are added in 90 ml deionized water, make Pidolidone, phosphoric acid
The concentration of disodium hydrogen and sodium hydroxide is respectively 0.091,0.024 and 0.039 mole every liter, add until completely dissolved carbamide,
Calcium nitrate and trisodium citrate, make the concentration of carbamide, calcium nitrate and trisodium citrate be 0.222,0.026 and 0.013 mole every
Rising, add in the reaction vessel being placed with polyvinyl alcohol and ibuprofen after being completely dissolved, polyvinyl alcohol selects molecular weight to be 105000
Polyvinyl alcohol 124, the addition of ibuprofen and polyvinyl alcohol and the mol ratio of calcium nitrate are respectively 1.65:1 and 1.22 × 10-3:1；
(2) furnace cooling after the reaction solution that step (1) is prepared being warming up to 100 DEG C and being incubated 24 hours, then calcium phosphate is sunk
The supernatant solution obtained after the centrifugation of shallow lake is the aqueous solution of ibuprofen high-dissolvability.
After tested, the pH value of the aqueous solution of ibuprofen high-dissolvability is 7.20, and ibuprofen dissolubility in aqueous reaches
To 8.80 milligrams every milliliter.
Claims (1)
1. utilize calcium phosphate precipitation auxiliary to improve ibuprofen method of dissolubility in water, it is characterized in that including following step
Rapid:
Pidolidone, disodium hydrogen phosphate and sodium hydroxide are first added in deionized water by step 1., make Pidolidone, phosphoric acid hydrogen
The concentration of disodium and sodium hydroxide is respectively 0.091,0.024 and 0.039 mole every liter, adds carbamide, nitre until completely dissolved
Acid calcium and trisodium citrate, making the concentration of carbamide, calcium nitrate and trisodium citrate is 0.056 ~ 0.222,0.026 and 0.013 to rub
You have every liter, is added to the reaction vessel being placed with polyvinyl alcohol and ibuprofen by solution after being completely dissolved, and polyvinyl alcohol selects to divide
Son amount is the polyvinyl alcohol 124 of 105000, and the addition of ibuprofen and polyvinyl alcohol and the mol ratio of calcium nitrate are respectively 1.65:
1 and 1.22 × 10-3:1；
The reaction solution that step 1 is prepared by step 2. is warming up to 100 DEG C and is incubated furnace cooling after 24 hours, then by calcium phosphate
The supernatant solution obtained after precipitation and centrifugal separation is the aqueous solution of ibuprofen high-dissolvability.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610502441.0A CN106110328A (en) | 2016-06-30 | 2016-06-30 | A kind of utilize calcium phosphate precipitation auxiliary improve ibuprofen method of dissolubility in water |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610502441.0A CN106110328A (en) | 2016-06-30 | 2016-06-30 | A kind of utilize calcium phosphate precipitation auxiliary improve ibuprofen method of dissolubility in water |
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| Publication Number | Publication Date |
|---|---|
| CN106110328A true CN106110328A (en) | 2016-11-16 |
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|---|---|---|---|
| CN201610502441.0A Pending CN106110328A (en) | 2016-06-30 | 2016-06-30 | A kind of utilize calcium phosphate precipitation auxiliary improve ibuprofen method of dissolubility in water |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513442A (en) * | 2003-06-26 | 2004-07-21 | 昆明市延安医院 | Prepn. and use of mixture of arginine-burfenum |
| CN1562966A (en) * | 2004-03-19 | 2005-01-12 | 中国药科大学 | New method for preparing brufen arginine salt |
| CN101175485A (en) * | 2005-03-22 | 2008-05-07 | 洛桑药物有限公司 | Solubilized ibuprofen |
| CN102727443A (en) * | 2012-06-29 | 2012-10-17 | 陈士忠 | Clathrate of mesoporous silicon oxide/Fe3O4 magnetic nano-grade complex and ibuprofen |
| CN104027313A (en) * | 2014-06-25 | 2014-09-10 | 山东理工大学 | Preparation method of octocalcium phosphate double-layer composite particle containing ibuprofen |
| CN104069073A (en) * | 2014-07-16 | 2014-10-01 | 山东理工大学 | Method for preparing calcium carbonate/octacalcium phosphate particles containing ibuprofen |
-
2016
- 2016-06-30 CN CN201610502441.0A patent/CN106110328A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513442A (en) * | 2003-06-26 | 2004-07-21 | 昆明市延安医院 | Prepn. and use of mixture of arginine-burfenum |
| CN1562966A (en) * | 2004-03-19 | 2005-01-12 | 中国药科大学 | New method for preparing brufen arginine salt |
| CN101175485A (en) * | 2005-03-22 | 2008-05-07 | 洛桑药物有限公司 | Solubilized ibuprofen |
| CN102727443A (en) * | 2012-06-29 | 2012-10-17 | 陈士忠 | Clathrate of mesoporous silicon oxide/Fe3O4 magnetic nano-grade complex and ibuprofen |
| CN104027313A (en) * | 2014-06-25 | 2014-09-10 | 山东理工大学 | Preparation method of octocalcium phosphate double-layer composite particle containing ibuprofen |
| CN104069073A (en) * | 2014-07-16 | 2014-10-01 | 山东理工大学 | Method for preparing calcium carbonate/octacalcium phosphate particles containing ibuprofen |
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| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20161116 |
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| RJ01 | Rejection of invention patent application after publication |