CN101464446A - Measuring method for inclusion rate of cyclodextrin inclusion compound - Google Patents
Measuring method for inclusion rate of cyclodextrin inclusion compound Download PDFInfo
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- CN101464446A CN101464446A CNA2007100931573A CN200710093157A CN101464446A CN 101464446 A CN101464446 A CN 101464446A CN A2007100931573 A CNA2007100931573 A CN A2007100931573A CN 200710093157 A CN200710093157 A CN 200710093157A CN 101464446 A CN101464446 A CN 101464446A
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- medicine
- inclusion
- inclusion compound
- rate
- cyclodextrin
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 28
- 229920000858 Cyclodextrin Polymers 0.000 title claims abstract description 24
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 56
- 229940079593 drug Drugs 0.000 claims abstract description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 239000000843 powder Substances 0.000 claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000007787 solid Substances 0.000 claims description 11
- 238000003556 assay Methods 0.000 claims description 7
- 239000002075 main ingredient Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 4
- 238000000967 suction filtration Methods 0.000 claims description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 238000000605 extraction Methods 0.000 abstract 2
- 238000001914 filtration Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 238000005303 weighing Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- 238000004108 freeze drying Methods 0.000 description 6
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 5
- 229960000711 alprostadil Drugs 0.000 description 5
- 238000007598 dipping method Methods 0.000 description 5
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 229960002117 triamcinolone acetonide Drugs 0.000 description 4
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 3
- 230000002421 anti-septic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 102000013142 Amylases Human genes 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940111205 diastase Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
Landscapes
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a method for measuring the inclusion rate of a cyclodextrin inclusion compound that is a trace drug, which adopts a menstruum extraction method that comprises the steps as follows: drug powders are infused in an organic solvent such as absolute ethyl alcohol, acetone and the like for a period of time and then processed through extraction filtration; residues are washed with the organic solvent and dried to obtain the inclusion compound or a mixture including the inclusion compound and a residual assistant agent; and the content of a main drug is measured, namely, the content of the inclusion compound is measured. The method solves the problem that the inclusion rate of the inclusion compound can be measured under the circumstances that free drugs are nonvolatile insoluble components and the concentrations of the inclusion compound and the free drugs are very low; in addition, the operation is simple, and the error is small; and no special instruments are needed.
Description
Technical field
The present invention relates to adopt the solvent partition method to measure the method for trace drug inclusion rate of cyclodextrin inclusion compound.
Background technology
Cyclodextrin (cyclodextrin, be called for short CD) be by diastase through the enzymolysis cyclization and the cyclic oligomer sugar compounds that connects with α-1,4 glycosidic bond of 6 to 8 glucose.Common have 3 kinds of α, β, γ.Wherein, β-CD is widely used in every field such as chemical industry, medicine, food, dyestuff, photographic material.Because cyclodextrin molecular has the characteristic of " interior hydrophobic, outer hydrophilic ", can comprise that organic and inorganic, biological micromolecule etc. forms inclusion compound with many guest molecules.Form the ripe preparation method of inclusion compound and have three kinds; Recrystallization method or coprecipitation (saturated water solution method), polishing, freeze-drying. wherein preceding two methods are more commonly used.
At present, for the mensuration of inclusion compound inclusion rate, existing method can only be used for the mensuration of volatile medicine inclusion rate mostly.After forming inclusion compound, volatile free drug is vapored away, remaining inclusion medicine, by freeze drying, spray drying etc., obtain pure inclusion compound.The content of measuring inclusion compound just can calculate inclusion rate.
When drug concentration is bigger, also can place a period of time by low temperature, allow inclusion compound separate out, obtain pure inclusion compound, also can calculate inclusion rate.
Because inclusion compound and free drug molecular weight difference are little, generally can not adopt gel column to separate.
In the solution there be much the assay method of inclusion rate, bibliographical information phase solubility method, mole ratio method, equimolar series method, Benesi-Hildebrand method etc. are arranged.Solid clathrates does not generally have strict inclusion rate, but can estimate the inclusion ratio by the content of mensuration guest molecule or by the DSC method.
These methods are operated all more complicated, and require that special instrument is arranged, and also require the amount of medicine can not be very low.
Existing technology is used for the mensuration of the inclusion rate of volatile matter cyclodextrin inclusion compound more, the mensuration of inclusion rate when perhaps the inclusion compound amount is very big.Under all extremely low situation of saturate and free drug concentration, be difficult to be collected pure inclusion compound exactly by above method, calculate inclusion rate.Under the very low situation of concentration, with the above-mentioned method of measuring inclusion rate in solution, error is very big.So above method all is not suitable for the mensuration of inclusion rate that low concentration, main ingredient are the medicine of solid powder substance.
Summary of the invention
Purpose of the present invention is at the deficiencies in the prior art, and the technical matters that solve is to propose a kind of free drug at the awkward water-soluble solid of normal temperature, and under all extremely low situation of inclusion compound and free drug concentration, accurately measures the method for inclusion rate.
In order to solve the problems of the technologies described above, technical conceive of the present invention is to adopt the solvent partition method, utilize one or more can dissolve free medicine but can not dissolve the organic solvent of inclusion compound and assistant, dipping medicine powder suction filtration after a period of time, use the organic solvent washing residue again, dry residue promptly obtains the potpourri of inclusion compound and residual assistant, and mensuration is through the content of the sample Chinese traditional medicine of above-mentioned processing with without the medicament contg of the sample of above-mentioned processing.Untreated samples Chinese traditional medicine content is the summation of inclusion medicine and free drug.Inclusion rate=medicament contg/medicament contg is untreated in the processing back.
This method is used for cyclodextrin inclusion compound, wherein contains cyclodextrin, main ingredient and pharmaceutically acceptable assistant.Wherein cyclodextrin comprises, 3 kinds of α, β, γ.Described pharmaceutic adjuvant comprises solubilizer, skeleton supporting agent, antioxidant, antiseptic etc.Because drug concentration is low, thus add a certain amount of assistant, to increase the volume of dry product.
Because medicament contg is very low, the error of this method also is very little.The amount of main ingredient is respectively 1% (g/g), 0.1% (g/g), and the actual inclusion rate that is is 50%.After the process solvent processing, inclusion rate only exceeds 0.25%, 0.025% than actual value respectively.If the main ingredient amount is littler, perhaps inclusion rate is higher, and this error is just littler.
The concrete operations step is as follows: main ingredient and cyclodextrin, advance cyclodextrin by paddling process with the medicine inclusion.In solution, add the skeleton supporting agent, can add antioxidant, antiseptic etc. if necessary.Solution by freezing or additive method is dry, is obtained the potpourri of inclusion medicine, free drug and cyclodextrin.Use absolute ethyl alcohol, perhaps other organic solvents dipping freeze-drying samples suction filtration after a period of time is used the organic solvent washing residue again, and dry residue promptly obtains the potpourri of inclusion compound and residual assistant.Mensuration is through the content of the sample Chinese traditional medicine of above-mentioned processing.Mensuration is without the medicament contg of the sample of above-mentioned processing.Untreated samples Chinese traditional medicine content is the summation of bag and medicine and free drug.Inclusion rate=medicament contg/medicament contg is untreated in the processing back.
Relative prior art, this method can be used for measuring the non-volatile material that is insoluble in water that normal temperature is solid, and under all extremely low situation of inclusion compound and free drug concentration, measure its inclusion rate, and under very micro-situation, also can accurately measure its inclusion rate, and error simple to operate is little, does not need very special instrument.This method also can be used for PGE
1The mensuration of inclusion rate of cyclodextrin inclusion compound.
Embodiment
Embodiment 1 takes by weighing PGE
15mg, beta-schardinger dextrin-300mg, sweet mellow wine 13g is equipped with inclusion compound by the solution stirring legal system, adds water to 250ml; Be filled into glass injection bottle, loading amount is the 1ml/ bottle, freeze drying; Get 20 bottles of dried frozen aquatic products mixings, precision takes by weighing 10 bottles amount and added 10ml absolute ethyl alcohol dipping 10 minutes; Decompress filter is removed absolute ethyl alcohol, uses 15ml absolute ethanol washing solid residue again; The drying under reduced pressure solid residue; Accurately take by weighing an amount of drying solid, measure the wherein content of PGE1; It is an amount of that precision takes by weighing untreated powder, measures the wherein content of PGE1; Can obtain its inclusion rate, inclusion rate=(handling the amount g/g of PGE1 in the inclusion compound)/(the amount g/g of PGE1 in the dried frozen aquatic products that is untreated) according to following formula calculating.The inclusion rate that records is 65.6%.
The investigation of dip time: get the same PGE1 Cyclodextrin saturate dried frozen aquatic products, when flooding 1 minute, the envelop rate that records is 97.5%; When flooding 2 minutes, the envelop rate that records is 86.5%; When flooding 20 minutes, the envelop rate that records is 65.4%.After adding solvent, dipping, up to no block, the freeze-drying piece all becomes powder.For free drug can dissolve fully, dip time is more than 10 minutes.
Embodiment 2 takes by weighing Triamcinolone Acetonide 6mg, beta-schardinger dextrin-300mg, and lactose 27g is equipped with inclusion compound by the solution stirring legal system, adds water to 200ml; Be filled into glass injection bottle, loading amount is the 1ml/ bottle, freeze drying; Get 20 bottles of dried frozen aquatic products mixings, precision takes by weighing 10 bottles amount and added 10ml acetone dipping 10 minutes; Decompress filter is removed acetone, washs solid residue with small amount of acetone again, the drying under reduced pressure solid residue; Accurately take by weighing an amount of drying solid, measure the wherein content of Triamcinolone Acetonide; It is an amount of that precision takes by weighing untreated powder, measures the wherein content of Triamcinolone Acetonide; (7) it is an amount of that precision takes by weighing untreated powder, measures the wherein content of Triamcinolone Acetonide; (9) calculate its inclusion rate.Inclusion rate is 75.9%.
Claims (6)
1. method of measuring the medicine inclusion rate of cyclodextrin inclusion compound, may further comprise the steps: flood medicine powder with organic solvent, suction filtration, use the organic solvent washing residue, dry residue, obtain the potpourri of inclusion compound and residual assistant, measure the wherein content and the untreated samples Chinese traditional medicine content of main ingredient, be calculated as follows inclusion rate:
Inclusion rate=medicament contg/medicament contg is untreated in the processing back.
2. as the assay method of the medicine inclusion rate of cyclodextrin inclusion compound of claim 1, it is characterized in that medicine embarrasses water-soluble solid, the weight ratio that medicine cyclodextrin inclusion compound and free drug account for is less than 0.01g/g.
3. as the assay method of the medicine inclusion rate of cyclodextrin inclusion compound of claim 1, it is characterized in that weight ratio that medicine cyclodextrin inclusion compound and free drug account for is less than 0.001g/g.
4. as the assay method of the medicine inclusion rate of cyclodextrin inclusion compound of claim 1, it is characterized in that organic solvent is ethanol, acetone, methyl alcohol, or their arbitrary proportion mixes.
5. the assay method of the medicine inclusion rate of cyclodextrin inclusion compound of claim 1 is characterized in that dip time is more than 10 minutes.
6. as the assay method of the medicine inclusion rate of cyclodextrin inclusion compound of claim 1, it is characterized in that medicine is a PGE
1
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100931573A CN101464446A (en) | 2007-12-18 | 2007-12-18 | Measuring method for inclusion rate of cyclodextrin inclusion compound |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100931573A CN101464446A (en) | 2007-12-18 | 2007-12-18 | Measuring method for inclusion rate of cyclodextrin inclusion compound |
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| Publication Number | Publication Date |
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| CN101464446A true CN101464446A (en) | 2009-06-24 |
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| CNA2007100931573A Pending CN101464446A (en) | 2007-12-18 | 2007-12-18 | Measuring method for inclusion rate of cyclodextrin inclusion compound |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104781283A (en) * | 2012-09-24 | 2015-07-15 | 罗门哈斯公司 | Method for measuring encapsulation efficiency for hydrophobic actives |
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2007
- 2007-12-18 CN CNA2007100931573A patent/CN101464446A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104781283A (en) * | 2012-09-24 | 2015-07-15 | 罗门哈斯公司 | Method for measuring encapsulation efficiency for hydrophobic actives |
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Open date: 20090624 |