CN115804760A - Tacrolimus nanocrystal capsule and preparation method thereof - Google Patents
Tacrolimus nanocrystal capsule and preparation method thereof Download PDFInfo
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- CN115804760A CN115804760A CN202211475033.2A CN202211475033A CN115804760A CN 115804760 A CN115804760 A CN 115804760A CN 202211475033 A CN202211475033 A CN 202211475033A CN 115804760 A CN115804760 A CN 115804760A
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- tacrolimus
- capsule
- nanocrystal
- preparation
- polysorbate
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- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 title claims abstract description 56
- 229960001967 tacrolimus Drugs 0.000 title claims abstract description 56
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 title claims abstract description 56
- 239000002775 capsule Substances 0.000 title claims abstract description 44
- 239000002159 nanocrystal Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 18
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims abstract description 10
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims abstract description 10
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 10
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 10
- 229940068968 polysorbate 80 Drugs 0.000 claims abstract description 10
- 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 claims abstract description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000008101 lactose Substances 0.000 claims abstract description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910002012 Aerosil® Inorganic materials 0.000 claims abstract description 7
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 7
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims abstract description 7
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims abstract description 7
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 7
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 7
- 239000008213 purified water Substances 0.000 claims abstract description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims abstract description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960000913 crospovidone Drugs 0.000 claims abstract description 3
- 238000000227 grinding Methods 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 7
- 238000011049 filling Methods 0.000 claims description 4
- 239000007902 hard capsule Substances 0.000 claims description 4
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 4
- 238000001694 spray drying Methods 0.000 claims description 4
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims description 3
- 239000011324 bead Substances 0.000 claims description 3
- 229910052726 zirconium Inorganic materials 0.000 claims description 3
- 238000001727 in vivo Methods 0.000 abstract description 8
- 238000010521 absorption reaction Methods 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 229940100691 oral capsule Drugs 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 description 5
- 238000002054 transplantation Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 241001647839 Streptomyces tsukubensis Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- PHTXVQQRWJXYPP-UHFFFAOYSA-N ethyltrifluoromethylaminoindane Chemical compound C1=C(C(F)(F)F)C=C2CC(NCC)CC2=C1 PHTXVQQRWJXYPP-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012716 precipitator Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a tacrolimus nanocrystal capsule, which consists of the following components: tacrolimus, polyethylene glycol 6000, polysorbate 80, microcrystalline cellulose, hydroxypropyl methylcellulose acetate succinate or hydroxypropyl cellulose phthalate, lactose, crospovidone, aerosil, magnesium stearate and purified water. The invention also discloses a preparation method of the tacrolimus nanocrystal capsule. The tacrolimus nanocrystal capsule provided by the invention is prepared and developed into an oral capsule preparation by taking tacrolimus as a medicinal active ingredient and adding some specific types and proportions of auxiliary materials according to the technical means described by the invention, the capsule preparation has improved bioavailability and small absorption difference in vivo.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a tacrolimus nanocrystal capsule and a preparation method thereof.
Background
Tacrolimus (acrolimus), a fermentation product isolated from streptomyces tsukubaensis, the chemical structure of which belongs to the 23-membered macrolide antibiotic. Is a strong novel immunosuppressant, mainly inhibits the release of interleukin-2 (L-2) to comprehensively inhibit the action of T lymphocytes, and is 100 times stronger than that of cyclosporine (CsA). In recent years, first line drugs for liver and kidney transplantation have been marketed in 14 countries such as japan and the usa. Clinical experiments show that the medicine has good curative effect when being applied to transplantation of heart, lung, intestine, bone marrow and the like. Meanwhile, tacrolimus also plays an active role in treating autoimmune diseases such as Atopic Dermatitis (AD), systemic Lupus Erythematosus (SLE), autoimmune ocular diseases and the like.
Tacrolimus is mainly used for preventing graft rejection after liver or kidney transplantation. And for the treatment of graft rejection uncontrolled by other immunosuppressive drugs applied after liver or kidney transplantation.
The existing tacrolimus oral preparations have 2 dosage forms of common capsules and slow-release capsules, but the existing tacrolimus oral preparations have the defects of low bioavailability, incomplete absorption of the preparations in gastrointestinal tracts after oral administration, large in-vivo absorption difference and the like. For example, after the oral preparation is taken, the absorption of some patients is rapid, and the peak is reached within 0.5 hour; in some patients, the drug appears to be continuously absorbed over a longer period of time, exhibiting a more or less plateau absorption effect.
Therefore, there is a need for a novel tacrolimus formulation that overcomes the above problems.
Disclosure of Invention
In order to solve the problems, the invention provides a tacrolimus nanocrystal capsule and a preparation method thereof, which improve the bioavailability of the medicine and have small absorption difference in vivo.
The invention discloses a tacrolimus nanocrystal capsule, which consists of the following components: tacrolimus, polyethylene glycol 6000, polysorbate 80, microcrystalline cellulose, hydroxypropyl methylcellulose acetate succinate or hydroxypropyl cellulose phthalate, lactose, crospovidone, aerosil, magnesium stearate and purified water.
The invention also discloses a preparation method of the tacrolimus nanocrystal capsule, which comprises the following steps:
a. micronizing tacrolimus;
b. adding polyethylene glycol 6000 and polysorbate 80 into appropriate amount of water, and stirring; b, adding the tacrolimus crushed in the step a, and uniformly stirring; then adding hydroxypropyl methylcellulose acetate succinate or hydroxypropyl cellulose phthalate, and mixing uniformly;
c. circularly grinding by using a grinder, and controlling the particle size of tacrolimus to obtain a nanocrystal suspension;
d. c, spray drying the nanocrystal suspension in the step c to obtain a drug-containing nanocrystal dry mixture; adding microcrystalline cellulose, lactose, polyvinylpolypyrrolidone, aerosil and magnesium stearate into the mixture, mixing uniformly, and filling into hard capsules.
Compared with the prior art, the invention has the beneficial effects that:
the tacrolimus nanocrystal capsule provided by the invention is prepared and developed into an oral capsule preparation by taking tacrolimus as a medicinal active ingredient and adding some specific types and proportions of auxiliary materials according to the technical means described by the invention, the capsule preparation has improved bioavailability and small absorption difference in vivo.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to specific embodiments, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
Example 1
The tacrolimus nanocrystal capsule disclosed by the embodiment comprises the following components in parts by weight:
| composition (A) | Content (wt.) |
| Tacrolimus | 5g |
| Polyethylene glycol 6000 | 3g |
| Polysorbate 80 | 1g |
| Microcrystalline cellulose | 100g |
| Hydroxypropyl cellulose phthalate | 15g |
| Lactose | 150g |
| Cross-linked polyvidone | 2g |
| Silica gel micropowder | 2g |
| Magnesium stearate | 2g |
| Purified water | Proper amount of |
The preparation method of the tacrolimus nanocrystal capsule comprises the following steps:
a. micronizing tacrolimus; specifically, a jet mill is used, the grinding pressure is controlled to be 0.6-0.8MPa, and the tacrolimus is subjected to superfine grinding;
b. adding polyethylene glycol 6000 and polysorbate 80 into appropriate amount of water, and stirring; b, adding the tacrolimus crushed in the step a, and uniformly stirring; adding hydroxypropyl cellulose phthalate, and mixing uniformly;
c. circularly grinding by using a grinder, wherein the grinding medium is 70% of zirconium beads with the diameter of 0.3mm, and the particle size of tacrolimus is controlled; starting a peristaltic pump at 10-30rpm, starting circular grinding at 1200rpm of a grinding machine for 1h, and sampling and detecting to obtain a nanocrystal suspension;
the particle size of tacrolimus in this example is required to be as follows:
d. c, spray drying the nanocrystal suspension in the step c to obtain a drug-containing nanocrystal dry mixture; adding microcrystalline cellulose, lactose, polyvinylpolypyrrolidone, aerosil and magnesium stearate into the mixture, mixing uniformly, and filling into hard capsules.
Example 2
The tacrolimus nanocrystal capsule disclosed by the embodiment comprises the following components in parts by weight:
| composition (I) | Content (wt.) |
| Tacrolimus | 5g |
| Polyethylene glycol 6000 | 2g |
| Polysorbate 80 | 1g |
| Microcrystalline cellulose | 100g |
| Hydroxypropyl methylcellulose acetate succinate | 15g |
| Lactose | 120g |
| Cross-linked polyvidone | 2g |
| Silica gel micropowder | 2g |
| Magnesium stearate | 2g |
| Purified water | Proper amount of |
The preparation method of the tacrolimus nanocrystal capsule comprises the following steps:
a. micronizing tacrolimus; specifically, a jet mill is used, the grinding pressure is controlled to be 0.6-0.8MPa, and the tacrolimus is subjected to superfine grinding;
b. adding appropriate amount of water into polyethylene glycol 6000 and polysorbate 80, and stirring; b, adding the tacrolimus crushed in the step a, and uniformly stirring; adding hydroxypropyl methylcellulose acetate succinate, and mixing;
c. circularly grinding by a grinder, wherein the grinding medium is 70% of zirconium beads with the diameter of 0.3mm, so as to control the particle size of tacrolimus; starting a peristaltic pump at 10-30rpm, starting circular grinding at 1200rpm of a grinding machine for 1h, and sampling and detecting to obtain a nanocrystal suspension;
the particle size of tacrolimus in this example is required to be as follows:
d. c, spray drying the nanocrystal suspension in the step c to obtain a drug-containing nanocrystal dry mixture; adding microcrystalline cellulose, lactose, polyvinylpolypyrrolidone, aerosil and magnesium stearate into the mixture, mixing uniformly, and filling into hard capsules.
Example 3
In vitro dissolution data and in vivo pharmacodynamic study were performed with the tacrolimus nanocrystal capsules prepared in example 2
1) In vitro dissolution test of tacrolimus nanocrystal capsules and ampleteprednol (tacrolimus capsules) -marketed capsules prepared in example 2
Table 1 shows the results of dissolution profile of the capsules prepared in example 2 in a solution having pH4.5
Table 2 shows the results of dissolution curves of marketed capsules in a pH4.5 solution
As can be seen from the in vitro dissolution data of the marketed capsules of tables 1 and 2 and example 2, the drug dissolution of the capsule formulation of example 2 is greater than that of the marketed capsules, and the Relative Standard Deviation (RSD) of each sample of example 2 is less than that of the marketed capsules at each sampling time point, indicating that the capsule of example 2 is better.
2) Tacrolimus nanocrystal capsules and Etai Tacrolimus capsules prepared in example 2-marketed capsules for in vivo pharmacodynamic study
12 healthy adult beagle dogs are randomly and alternately orally taken 5mg each of the capsule (T) and the marketed capsule (R, tacrolimus sustained release capsule, ansteilay pharmaceutical (China) Co., ltd.) of example 2, then blood is taken from the hind leg vein, 1ml of blood is taken at 0h (before administration), 0.5h, 1.0h, 1.5h, 2.0h, 3.0h, 4.0h, 6.0h, 8.0h, 12h and 24h respectively, serum is obtained by centrifugation, precipitator-containing precipitated protein is added, supernatant is collected, the supernatant is dried at room temperature by blowing, 100 microliters of acetonitrile aqueous solution is added for redissolving, and then the Tacrolimus content is detected on a machine. The results are shown in Table 3.
Table 3 shows data for capsules (T) and reference commercial preparations (R)
As can be seen from the above table, the mean value of the Cmax ratio of tacrolimus for capsule (T) and reference commercial preparation (R) is 1.14 and CV% is 0.93, indicating that capsule (T) (example 2) is more absorbed in vivo than the reference preparation, and the coefficient of variation in vivo is less than that of the reference commercial preparation (R).
While only certain embodiments of the present invention have been described, it should be understood that various other changes and modifications could be made by one skilled in the art without departing from the spirit and scope of the invention.
Claims (4)
1. A tacrolimus nano crystal capsule is characterized in that,
the capsule consists of the following components:
tacrolimus, polyethylene glycol 6000, polysorbate 80, microcrystalline cellulose, hydroxypropyl methylcellulose acetate succinate or hydroxypropyl cellulose phthalate, lactose, crospovidone, aerosil, magnesium stearate and purified water;
the preparation method of the capsule comprises the following steps:
a. micronizing tacrolimus;
b. adding appropriate amount of water into polyethylene glycol 6000 and polysorbate 80, and stirring; b, adding the tacrolimus crushed in the step a, and uniformly stirring; then adding hydroxypropyl methylcellulose acetate succinate or hydroxypropyl cellulose phthalate, and mixing uniformly;
c. circularly grinding by using a grinder, and controlling the particle size of tacrolimus to obtain a nanocrystal suspension;
d. c, spray drying the nanocrystal suspension in the step c to obtain a drug-containing nanocrystal dry mixture; adding microcrystalline cellulose, lactose, polyvinylpolypyrrolidone, aerosil and magnesium stearate into the mixture, mixing uniformly, and filling into hard capsules.
2. The tacrolimus nanocrystal capsule of claim 1, wherein the total amount of the polyethylene glycol 6000 and the polysorbate 80 is 1-6% of the capsule.
3. A tacrolimus nanocrystal capsule according to claim 2 wherein the particle size of tacrolimus in step c requires: d10 is 0.01-0.1 μm, D50 is 0.08-0.15 μm, and D90 is 1.0-4.5 μm.
4. A tacrolimus nanocrystal capsule according to claim 3 wherein the grinding media in step c is zirconium beads of 0.2mm to 0.8mm diameter loaded at 40 to 90%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211475033.2A CN115804760A (en) | 2022-11-23 | 2022-11-23 | Tacrolimus nanocrystal capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211475033.2A CN115804760A (en) | 2022-11-23 | 2022-11-23 | Tacrolimus nanocrystal capsule and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN115804760A true CN115804760A (en) | 2023-03-17 |
Family
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|---|---|---|---|
| CN202211475033.2A Pending CN115804760A (en) | 2022-11-23 | 2022-11-23 | Tacrolimus nanocrystal capsule and preparation method thereof |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1820759A (en) * | 2006-03-20 | 2006-08-23 | 复旦大学 | Tacrolimus solid dispersion and its preparing method |
| US20110021553A1 (en) * | 2008-02-05 | 2011-01-27 | Rodrigo Ivan Ramirez Monetta | Immunosuppressive macrolide powder for oral suspension |
| CN104887626A (en) * | 2015-05-29 | 2015-09-09 | 沈阳药科大学 | Preparation method of nano suspension |
| CN105534943A (en) * | 2015-12-26 | 2016-05-04 | 蔡丝英 | Tacrolimus quick-release preparation and preparation method thereof |
| WO2016119114A1 (en) * | 2015-01-27 | 2016-08-04 | 上海秀新臣邦医药科技有限公司 | Puerarin nanocrystalline capsule and preparation method therefor |
| CN106137971A (en) * | 2015-11-17 | 2016-11-23 | 南京瑞捷医药科技有限公司 | A kind of tacrolimus dispersion and slow releasing composition thereof and preparation method |
| CN108904459A (en) * | 2018-09-11 | 2018-11-30 | 南京瑞捷医药科技有限公司 | A kind of preparation method of tacrolimus solid dispersion tablet |
-
2022
- 2022-11-23 CN CN202211475033.2A patent/CN115804760A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1820759A (en) * | 2006-03-20 | 2006-08-23 | 复旦大学 | Tacrolimus solid dispersion and its preparing method |
| US20110021553A1 (en) * | 2008-02-05 | 2011-01-27 | Rodrigo Ivan Ramirez Monetta | Immunosuppressive macrolide powder for oral suspension |
| WO2016119114A1 (en) * | 2015-01-27 | 2016-08-04 | 上海秀新臣邦医药科技有限公司 | Puerarin nanocrystalline capsule and preparation method therefor |
| CN104887626A (en) * | 2015-05-29 | 2015-09-09 | 沈阳药科大学 | Preparation method of nano suspension |
| CN106137971A (en) * | 2015-11-17 | 2016-11-23 | 南京瑞捷医药科技有限公司 | A kind of tacrolimus dispersion and slow releasing composition thereof and preparation method |
| CN105534943A (en) * | 2015-12-26 | 2016-05-04 | 蔡丝英 | Tacrolimus quick-release preparation and preparation method thereof |
| CN108904459A (en) * | 2018-09-11 | 2018-11-30 | 南京瑞捷医药科技有限公司 | A kind of preparation method of tacrolimus solid dispersion tablet |
Non-Patent Citations (1)
| Title |
|---|
| 吴正红等主编: "《药剂学》", 30 April 2020, 北京：中国医药科技出版社 * |
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