CN109718221B - Icariin preparation - Google Patents
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- CN109718221B CN109718221B CN201711043933.9A CN201711043933A CN109718221B CN 109718221 B CN109718221 B CN 109718221B CN 201711043933 A CN201711043933 A CN 201711043933A CN 109718221 B CN109718221 B CN 109718221B
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- icariin
- preparation
- beta cyclodextrin
- hydroxypropyl beta
- sodium carboxymethyl
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- TZJALUIVHRYQQB-XFDQAQKOSA-N Icariin Natural products O(C)c1ccc(C2=C(O[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)C(=O)c3c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O4)c(C/C=C(\C)/C)c3O2)cc1 TZJALUIVHRYQQB-XFDQAQKOSA-N 0.000 title claims abstract description 55
- TZJALUIVHRYQQB-UHFFFAOYSA-N icariine Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(C)O2)O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-UHFFFAOYSA-N 0.000 title claims abstract description 55
- TZJALUIVHRYQQB-XLRXWWTNSA-N icariin Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-XLRXWWTNSA-N 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title claims abstract description 44
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 25
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 25
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 25
- 238000000227 grinding Methods 0.000 claims abstract description 20
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims abstract description 19
- 239000000725 suspension Substances 0.000 claims abstract description 16
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 14
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 14
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 14
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 14
- 239000007864 aqueous solution Substances 0.000 claims abstract description 13
- 238000003756 stirring Methods 0.000 claims abstract description 12
- 239000011324 bead Substances 0.000 claims abstract description 11
- 238000001694 spray drying Methods 0.000 claims abstract description 11
- 239000002775 capsule Substances 0.000 claims abstract description 9
- 239000008187 granular material Substances 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000008188 pellet Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 33
- 238000004090 dissolution Methods 0.000 abstract description 22
- 229940079593 drug Drugs 0.000 abstract description 18
- 239000006187 pill Substances 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 4
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 102220042174 rs141655687 Human genes 0.000 description 8
- 238000007873 sieving Methods 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- TUUXBSASAQJECY-UHFFFAOYSA-N 3,5,7-trihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C(CC=C(C)C)=C2O1 TUUXBSASAQJECY-UHFFFAOYSA-N 0.000 description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 6
- 239000003223 protective agent Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000001238 wet grinding Methods 0.000 description 5
- 241000893536 Epimedium Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- CTGVBHDTGZUEJZ-UHFFFAOYSA-N Noricaritin Natural products CC(C)(O)CCC1=C(O)C=C(O)C(C(C=2O)=O)=C1OC=2C1=CC=C(O)C=C1 CTGVBHDTGZUEJZ-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 235000018905 epimedium Nutrition 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 2
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 2
- 239000012738 dissolution medium Substances 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- -1 flavonoid glycoside compounds Chemical class 0.000 description 2
- 229910021485 fumed silica Inorganic materials 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 241000133570 Berberidaceae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003262 anti-osteoporosis Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- 229960000878 docusate sodium Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 229930182486 flavonoid glycoside Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007056 liver toxicity Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and in particular relates to an icariin preparation which contains icariin, sodium carboxymethyl cellulose and hydroxypropyl beta cyclodextrin. The preparation method comprises adding icariin into aqueous solution of sodium carboxymethylcellulose and hydroxypropyl beta cyclodextrin, stirring, grinding with bead mill, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and making into corresponding capsule, granule or other pharmaceutical preparation. Compared with the prior art, the invention has the advantages of good drug stability, quick dissolution and simple process.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an icariin preparation.
Background
Icaritin (IT) is a polyhydroxy flavonoid monomer component in Epimedium plant of berberidaceae, and has the following structural formula:
pharmacological research shows that IT has stronger anti-osteoporosis activity than other flavonoid glycoside compounds in epimedium, and has the functions of promoting osteoblast activity and inhibiting osteoclast activity in vitro. Icariin is taken as one of main active ingredients, attracts attention of a plurality of scholars at home and abroad in recent years, and carries out intensive and extensive research on pharmacological actions of the icariin, and the results so far find that the main physiological activity of the icariin is in improving cardiovascular and cerebrovascular system functions, enhancing organism immunity and regulating endocrine, and has the effects of resisting tumor, resisting liver toxicity, resisting hypoxia reoxygenation, strengthening bones and the like.
Icariin is poorly soluble, slightly soluble in methylene chloride and ethyl acetate, practically insoluble in methanol, absolute ethanol and water, practically insoluble or insoluble in buffers of different pH. Its extremely low solubility necessarily affects drug absorption. There is no icariin preparation in clinic. It is therefore particularly important to find a formulation that increases the dissolution rate of icariin.
CN101485630B discloses an icariin liposome, which overcomes the defects of poor in vitro dissolution and low bioavailability of icariin. However, the liposome is produced in a low yield and is difficult to handle in practical production.
CN101513388A discloses an icariin microemulsion and a preparation method thereof, which is prepared by dissolving active ingredients in grease, adding emulsifying agent, auxiliary emulsifying agent and water, and the microemulsion with the particle size of 10-100 nm. However, a large amount of surfactant brings a large amount of toxic and side effects to human body.
CN101637467a discloses an icariin phospholipid complex or a cycloicariin phospholipid complex, which greatly improves their solubility and solves the disadvantages of poor water solubility and fat solubility and low bioavailability. However, the preparation process is complex, and a large amount of organic solvent is used, which is not beneficial to environmental protection.
CN105982869a icariin tablet is prepared by dissolving icariin and hydroxypropyl cellulose in diethylene glycol monoethyl ether, adding fumed silica, adsorbing, and making into tablet. However, after long-term storage, as the solvent volatilizes, the icariin will precipitate, resulting in slow dissolution of the drug.
Disclosure of Invention
The inventors have tried to improve the solubility of the medicine by increasing the specific surface area by reducing the particle size of the medicine in consideration of the poor water solubility of epimedium, and have found that the solubility is only slightly increased when the medicine is pulverized to about 5 microns, and the promotion of in vivo absorption is estimated to be limited.
Further, the inventors consider that wet grinding technology can be adopted to reduce the granularity of the medicine to about 200nm, and the solubility is obviously increased, but the wet grinding needs to use surfactants such as sodium dodecyl sulfate, docusate sodium, cetyl trimethyl ammonium bromide and the like, and the surfactants have certain toxicity as charge protective agents. In addition, three-dimensional protecting agent such as hydroxypropyl cellulose, povidone, tween, etc. is also required. In the experiment, if no charge protective agent is added, the granularity of the medicine can only be ground to about 600nm, and the medicine is mainly aggregated after grinding.
The inventor tries to adopt wet grinding technology, but does not add charge protective agent to improve the safety of medicine taking, after a large number of exploratory experiments, the inventor's hypothesis is proved by experimental results because if sodium carboxymethylcellulose with good safety is selected as a thickener, the sodium carboxymethylcellulose plays a role of a three-dimensional protective agent and also plays a role of a charge protective agent due to sodium ions. The drug particles can be ground to 170nm, and the solubility is also greatly improved, but when the drug particles are further processed into tablets or capsules and subjected to dissolution test, the drug is slowly dissolved, probably because sodium carboxymethyl cellulose is used as a powerful adhesive, so that the drug release is delayed.
To solve the problem of slow dissolution of the drug, the inventors tried to add a disintegrant, but the effect was not obvious because the disintegrant such as with the drug, sodium carboxymethyl cellulose was ground, the particle size of the disintegrant became small, the disintegrating effect became poor; if the medicine and sodium carboxymethyl cellulose are ground and then the disintegrating agent is added, only the tablet or capsule can be disintegrated quickly, and the dissolution of the medicine after the preparation is disintegrated can not be promoted. Therefore, the inventor continues to carry out experiments, and selects substances with larger viscosity in aqueous solution, such as hydroxypropyl cellulose, and the like, so as to reduce the concentration of sodium cellulose; and finally, only hydroxypropyl beta cyclodextrin and sodium carboxymethyl cellulose are used together, so that the effect of improving the drug dissolution is best, and experiments show that the drug dissolution is rapid.
The invention is realized by the following technical scheme:
an icariin preparation contains icariin, sodium carboxymethyl cellulose, and hydroxypropyl beta cyclodextrin; the preparation method comprises the following steps:
(1) Adding proper amount of icariin into aqueous solution of sodium carboxymethyl cellulose and hydroxypropyl beta cyclodextrin, and stirring uniformly;
(2) Grinding the aqueous solution in the step (1) through a bead mill to obtain a mixed solution;
(3) Spray drying the suspension of step (2) on microcrystalline cellulose pellets by a fluidized bed.
The icariin preparation is characterized in that the icariin preparation in the preparation method step (1) is crushed and screened by a 100-120-mesh sieve.
The icariin preparation is characterized in that the weight ratio of the icariin to the sodium carboxymethyl cellulose is 1:0.02-0.08.
The icariin preparation is characterized in that the weight ratio of the icariin to the hydroxypropyl beta cyclodextrin is 1:1-8.
According to the technical scheme, the medicine dissolution rate is more than 96.9%.
The weight ratio of the icariin to the sodium carboxymethyl cellulose of the icariin preparation is 1:0.02-0.06, preferably 1:0.03.
The weight ratio of the icariin to the hydroxypropyl beta cyclodextrin of the icariin preparation is 1:1-5, preferably 1:3.
The dissolution rate of the medicine in the technical proposal is more than 98.5 percent.
The icariin preparation can be a capsule, a tablet, a granule and a pharmaceutically acceptable dosage form.
A method for preparing the capsule comprises encapsulating microcrystalline cellulose pill core into capsule shell.
A method for preparing the granule comprises packaging microcrystalline cellulose pill core.
The icariin preparation provided by the invention has the following advantages:
1. the icariin preparation is combined with sodium carboxymethyl cellulose and hydroxypropyl beta cyclodextrin in a certain proportion, and a wet grinding technology is adopted to increase the dissolution rate of the medicine.
2. The wet grinding does not use a surfactant with certain toxicity, so that the safety is higher
3. The manufacturing method is simple to operate and suitable for industrial mass production.
Detailed Description
The following examples further describe the beneficial effects of the present invention and are intended to be illustrative only and not to limit the scope of the present invention, as obvious changes and modifications to those skilled in the art in light of the present invention are intended to be included within the scope of the present invention.
Example 1
The preparation process comprises the following steps:
grinding icariin, sieving with 100 mesh sieve, adding into aqueous solution of sodium carboxymethylcellulose and hydroxypropyl beta cyclodextrin, stirring, grinding with bead mill for 45min for D90=220 nm, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and encapsulating.
Example 2
The preparation process comprises the following steps:
grinding icariin, sieving with 120 mesh sieve, adding into aqueous solution of sodium carboxymethylcellulose and hydroxypropyl beta cyclodextrin, stirring, grinding with bead mill for 60min for D90=210 nm, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and encapsulating.
Example 3
The preparation process comprises the following steps:
grinding icariin, sieving with 100 mesh sieve, adding into aqueous solution of sodium carboxymethylcellulose and hydroxypropyl beta cyclodextrin, stirring, grinding with bead mill for 45min for D90=180nm, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and encapsulating.
Example 4
The preparation process comprises the following steps:
grinding icariin, sieving with 120 mesh sieve, adding into aqueous solution of sodium carboxymethylcellulose and hydroxypropyl beta cyclodextrin, stirring, grinding with bead mill for 60min for D90=280 nm, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and encapsulating.
Comparative example 1
The preparation process comprises the following steps:
grinding icariin, sieving with 100 mesh sieve, adding into aqueous solution of sodium dodecyl sulfate and hydroxypropyl beta cyclodextrin, stirring, grinding with bead mill for 45min for D90=540 nm, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and encapsulating.
Comparative example 2
The preparation process comprises the following steps:
grinding icariin, sieving with 100 mesh sieve, adding into aqueous solution of sodium carboxymethylcellulose and hydroxypropyl cellulose, stirring, grinding with bead mill for 45min for D90=240 nm, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and encapsulating.
Comparative example 3
The preparation process comprises the following steps:
grinding icariin, sieving with 100 mesh sieve, adding into water solution of hexadecyl trimethyl ammonium bromide and hydroxypropyl beta cyclodextrin, stirring, grinding with bead mill for 45min for D90=450 nm, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and encapsulating.
Comparative example 4
The preparation process comprises the following steps:
dissolving icariin in diethylene glycol monoethyl ether, adding hydroxypropyl cellulose, stirring to dissolve, adding fumed silica of prescribed amount for adsorption, mixing with microcrystalline cellulose, sodium carboxymethyl starch, and magnesium stearate, and tabletting
Comparative example 5
The preparation process comprises the following steps:
grinding icariin, sieving with 100 mesh sieve, adding into aqueous solution of sodium carboxymethylcellulose and hydroxypropyl beta cyclodextrin, stirring, grinding with bead mill for 45min for D90=2.1 μm, spray drying the suspension on microcrystalline cellulose pill core with fluidized bed, and encapsulating.
Verification embodiment
Dissolution test of Epimedium preparation:
measuring the dissolution rate of the preparation by high performance liquid chromatography, and using octadecylsilane chemically bonded silica chromatographic column; taking 0.1% phosphoric acid solution-methanol (20:80) as a mobile phase; the flow rate is 1.0ml per minute; the detection wavelength was 270nm. The dissolution rate measurement method refers to the second method of the second appendix of 2010 edition of Chinese pharmacopoeia. The dissolution medium is self-defined. Taking the preparation prepared in each example, taking water (900 ml) as a dissolution medium, operating at 75rpm according to law, filtering a proper amount of the solution after 5min, discarding at least 10ml of primary filtrate, and taking the subsequent filtrate as a sample solution. And taking a proper amount of icariin reference substance, precisely weighing, adding methanol for dissolving and diluting to prepare a solution with the concentration of about 5.5 mug in each 1ml serving as the reference substance solution. Precisely measuring 10 μl of each of the above two solutions, respectively injecting into a liquid chromatograph, recording the chromatogram, and calculating the dissolution of icariin in the sample solution according to external standard method and peak area.
Results of the measurements of the examples
In the embodiments 1-4 of the invention, the particle size of the drug suspension is small, and the drug is dissolved out quickly; example 4 the drug particles were able to grind to 280nm with slightly lower dissolution compared to examples 1-3. In comparative example 1, sodium dodecyl sulfate is used to replace sodium carboxymethyl cellulose, the particle size of the suspension is large, the dissolution of the medicine is slow, and after accelerated investigation, the dissolution drop is obvious, because the dosage of sodium dodecyl sulfate is small, the medicine is easy to aggregate in the suspension, and after the prepared preparation is placed, the medicine is also aggregated to cause slow dissolution; comparative example 2, hydroxypropyl cellulose was used instead of hydroxypropyl beta cyclodextrin, the particle size of the suspension was almost the same, but the dissolution was slow; comparative example 3, replacing sodium carboxymethyl cellulose with cetyltrimethylammonium bromide, was as effective as sodium dodecyl sulfate; comparative example 4, using the prior art, accelerated investigation, the dissolution was slow, probably due to precipitation of the drug by solvent evaporation, despite rapid dissolution; in comparative example 5, sodium carboxymethyl starch was used instead of sodium carboxymethyl cellulose, and the particle size of the suspension was large, probably because sodium carboxymethyl starch did not have a suspending agent effect, and the drug dissolution was slow.
Claims (6)
1. An icariin preparation is characterized in that the preparation contains icariin, sodium carboxymethyl cellulose and hydroxypropyl beta cyclodextrin; the weight ratio of the icariin to the sodium carboxymethyl cellulose is 1:0.02-0.04; the weight ratio of the icariin to the hydroxypropyl beta cyclodextrin is 1:1-3; the preparation method comprises the following steps:
(1) Adding proper amount of icariin into aqueous solution of sodium carboxymethyl cellulose and hydroxypropyl beta cyclodextrin, and stirring uniformly;
(2) Grinding the aqueous solution in the step (1) through a bead mill to obtain a mixed solution;
(3) Spray drying the suspension of step (2) on microcrystalline cellulose pellets by a fluidized bed.
2. The icariin preparation according to claim 1, wherein the icariin preparation in the preparation method step (1) is crushed and screened through a 100-120 mesh screen.
3. The icariin preparation according to any one of claims 1-2, wherein the preparation is a pharmaceutically acceptable dosage form.
4. The icariin preparation according to claim 3, wherein the preparation is a capsule, a tablet or a granule.
5. A process for preparing a capsule according to claim 4, wherein the product obtained in step (3) according to claim 1 is filled into a capsule shell.
6. A process for preparing the granules according to claim 4, wherein the product obtained in the step (3) according to claim 1 is packaged.
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| CN114224873B (en) * | 2021-11-19 | 2023-03-24 | 安徽金源药业有限公司 | Preparation method of icariin sustained-release nano capsule |
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| CN105412002A (en) * | 2014-09-17 | 2016-03-23 | 山东新时代药业有限公司 | Anhydroicaritin oral preparation and preparation method thereof |
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| CN105412002A (en) * | 2014-09-17 | 2016-03-23 | 山东新时代药业有限公司 | Anhydroicaritin oral preparation and preparation method thereof |
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