CN1919184A - Mycophenolate mofetile dispersed tablet and preparation method thereof - Google Patents
Mycophenolate mofetile dispersed tablet and preparation method thereof Download PDFInfo
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- CN1919184A CN1919184A CN 200610126992 CN200610126992A CN1919184A CN 1919184 A CN1919184 A CN 1919184A CN 200610126992 CN200610126992 CN 200610126992 CN 200610126992 A CN200610126992 A CN 200610126992A CN 1919184 A CN1919184 A CN 1919184A
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- mycophenolate mofetil
- dispersible tablet
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- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 title description 7
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 title description 4
- 229940014456 mycophenolate Drugs 0.000 title 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims abstract description 44
- 229960004866 mycophenolate mofetil Drugs 0.000 claims abstract description 37
- 239000007919 dispersible tablet Substances 0.000 claims abstract description 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 19
- 239000000945 filler Substances 0.000 claims abstract description 7
- 239000000314 lubricant Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 5
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 5
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 5
- 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 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 235000019202 steviosides Nutrition 0.000 claims description 4
- 229920003081 Povidone K 30 Polymers 0.000 claims description 3
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 3
- 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 description 2
- 108010011485 Aspartame Proteins 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- 206010013786 Dry skin Diseases 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 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 description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical group O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000007779 soft material Substances 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 229940013618 stevioside Drugs 0.000 claims description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 230000008901 benefit Effects 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 5
- 238000010521 absorption reaction Methods 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 2
- 239000006185 dispersion Substances 0.000 abstract 1
- 235000003599 food sweetener Nutrition 0.000 abstract 1
- 230000009747 swallowing Effects 0.000 abstract 1
- 239000003765 sweetening agent Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 7
- 229960003444 immunosuppressant agent Drugs 0.000 description 6
- 230000001861 immunosuppressant effect Effects 0.000 description 6
- 239000003018 immunosuppressive agent Substances 0.000 description 6
- 238000002054 transplantation Methods 0.000 description 5
- 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 4
- 108010036949 Cyclosporine Proteins 0.000 description 4
- 229960001265 ciclosporin Drugs 0.000 description 4
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 210000003714 granulocyte Anatomy 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 229960000951 mycophenolic acid Drugs 0.000 description 3
- 230000003448 neutrophilic effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 1
- -1 2-ethyl Chemical group 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
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- 206010047115 Vasculitis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
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- 238000004458 analytical method Methods 0.000 description 1
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- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
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- 230000008859 change Effects 0.000 description 1
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- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 235000013928 guanylic acid Nutrition 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention relates to a mycophenolate mofetil dispersible tablet and process for preparation, wherein the dispersible tablet comprises the following raw materials (by weight ratio): mycophenolate mofetil 125-500 parts, filling agent 30-120 parts, crumbling agent 25-150 parts, sweetener 6-24 parts, and lubricant 0.5-5 parts. The mycophenolate mofetil has the advantages of shorter disintegration period, better dispersion state, faster medicament dissolving, quicker absorption, and higher biological availability, thus is especially suitable for the elder people and patients suffering from swallowing difficulty.
Description
Technical field
The present invention relates to pharmaceutical preparation, specifically, is a kind of immunosuppressant, i.e. mycophenolate mofetil dispersible tablet.
Background technology
In accepting the immunosuppressant that the organ transplant patient takes all the life now, Mycophenolate Mofetil (Mycophenolate Mofetil, MMF) be a kind of representative drugs with milestone significance, become the immunosuppressant of world's sales volume first, be widely used among adult and child's kidney, heart and the liver transplant patient.MMF combines efficiently originally, low toxicity, good and clinical curative effect and safety, and reliable characteristics such as pharmacokinetic properties, obtain generally acknowledging of domestic and international clinical boundary, be applied to the treatment of the heart, renal transplantation rejection and immune disease such as lupus nephritis, vasculitis etc. at present.
(mycophenolate mofetil is that (mycophenolic acid, 2-ethyl ester analog derivative MPA) take off esterification and form the metabolite MPA with immunosuppressive activity Mycophenolic Acid in vivo after the oral absorption MMF) to Mycophenolate Mofetil.MPA is efficient, selectivity, noncompetitive, reversible hypoxanthine mononucleotide dehydrogenase (IMPDH) inhibitor, the classical route of synthesis that can suppress guanylic acid, the propagation of selective exclusion T and bone-marrow-derived lymphocyte, transplant rejection and autoimmune disease all there is significant curative effect, and few side effects has shown good prospects for application.Summary is got up, and the mechanism of action of MMF has following specificity: (1) selectivity suppresses the classical route of synthesis of lymphocyte guanine, to non-lymphocyte and/or organ free of toxic effects; (2) directly suppress B cell proliferation, and ciclosporin does not suppress the effect that antibody forms; (3) efficiently reduce the activity of adhesion molecule, suppress vascular smooth muscle cell proliferation, can prevent and treat the vascular rejection and reduce the generation of chronic rejection.MMF can be used for accepting kidney of the same race, heart or liver transplantation patient's organ rejection response in addition, can use simultaneously with ciclosporin and adrenocortical hormone.The U.S. (ATC 2004) has the following advantages based on the immunosuppressant scheme of MMF: 1. help improving patient's survival rate to surpassing studies show that of 61000 routine cases; 2. toxicity is low; 3. acute and chronic rejection significantly reduces.Studies confirm that through Clinical Application: after MMF replaces AZA (azathioprine), it can effectively prevent and treat posttransplantation acute rejection, reduced the incidence rate of 50% acute cellular rejection, prolong the graft long-term surviving, and intractable repulsion and the vascular of anti-hormone and anti-ATG/ALG are repelled the effect that " treatment of treatment property " also arranged.
Summary of the invention
First purpose of the present invention provides a kind of mycophenolate mofetil dispersible tablet.
Another object of the present invention provides the preparation method of this mycophenolate mofetil dispersible tablet.
In order to achieve the above object, the present invention is by the following technical solutions:
This kind mycophenolate mofetil dispersible tablet, contain the raw material of following weight portion:
Mycophenolate Mofetil 125-500 part
Filler 30-120 part
Disintegrating agent 25-150 part
Sweeting agent 6-24 part
Lubricant 0.5-5 part.
In the described disintegrating agent, add in 20-100 part, 5-50 adds especially.
Described filler is selected from a kind of or its combination in lactose, mannitol, starch, pregelatinized Starch, microcrystalline Cellulose, micropowder silica gel, the sucrose.
Described disintegrating agent is selected from a kind of or its combination in low-substituted hydroxypropyl cellulose, carboxymethylstach sodium, polyvinylpolypyrrolidone, the crosslinked carboxymethyl fecula sodium.
Described sweeting agent is selected from stevioside, Aspartame, glucide and/or xylitol.
Described lubricant is selected from magnesium stearate or/and Pulvis Talci.
Preferably, described raw material and weight portion thereof are: 250 parts of Mycophenolate Mofetil, 40 parts of microcrystalline Cellulose, 30 parts of polyvinylpolypyrrolidone, 20 parts of low-substituted hydroxypropyl celluloses, 12 parts of steviosides, 2 parts of magnesium stearates.
This mycophenolate mofetil dispersible tablet makes by the following technical solutions:
A, each raw material pulverizing is crossed 80 mesh sieves;
B, take by weighing Mycophenolate Mofetil, filler, in the disintegrating agent and the sweeting agent that add, mix homogeneously;
C, adding 5% 30 POVIDONE K 30 BP/USP
30Alcoholic solution system soft material is with 24 mesh sieve system wet granulars;
D, wet granular be in 50 ℃ of dryings, and dry back is with 24 mesh sieve granulate, and even with the disintegrating agent that adds, mix lubricant again, tabletting is packed promptly.
The experimenter puts into mouth with 4 of mycophenolate mofetil dispersible tablets, takes with 200ml warm water.
First dose of dosage this product of prevention renal transplantation rejection should be oral within post-transplantation 72 hours.In renal transplant patient's usefulness, recommend each 1 gram, one day twice (daily dose is 2 grams).Though each 1.5 grams, one day twice (daily dose is 3 grams) used in clinical trial, and was safety and effective, not the advantage on the effect.The patient who accepts this product 2 grams every day is better than the patient who accepts 3 grams aspect overall security.This product should be used simultaneously with the ciclosporin and the corticosteroid of standard dose.
Treat the dosage of intractable renal transplant rejection clinical in, be each 1.5 grams to the treatment and the maintenance dose of intractable repulsion, one day twice (daily dose is 3 grams).So, every day 3 gram dosage recommended be used for clinical.This product should be used simultaneously with the ciclosporin and the corticosteroid of standard dose.
The patient that special consumption instructs neutrophilic granulocyte to reduce: (the neutrophilic granulocyte counting, absolute number is less than 1.3 * 10 if neutrophilic granulocyte reduces
3/ microlitre), answers interruption of the administration or decrement, should examine patient simultaneously.
The patient of severe renal functional lesion: for the renal transplant patient that severe chronic renal function injury (glomerular filtration rate less than 25 ml/min/1.73 square metre) is arranged, tiding over postoperative after date early, should avoid share greater than each 1 gram, semidiurnal dosage.And these patients need tight the observation.
The patient that renal transplantation thing function postpones: the patient to the postoperative graft function postpones need not to adjust dosage.
The patient of serious hepatic insufficiency: the renal transplant patient with serious liver parenchyma disease be need not dose titration.(see [pharmacokinetics].
Old man (more than or equal to 65 years old): to the renal transplant patient, oral each 1 gram of being recommended, every day, 2 times dosage was suitable to the old people.
The anaphylaxis of [contraindication] this product is observed.Therefore, this product is forbidden in the patient that allergy is arranged for Mycophenolate Mofetil and Mycophenolic Acid.
The patient of immunosuppressant treatment is accepted in warning, comprises drug combination, accepts this product as the partial immunity suppression therapy, and the danger that lymphoma and other malignant tumor take place increases, particularly skin.(seeing [untoward reaction]).Dangerous relevant with the immunosuppressant intensity and the course of treatment, have nothing to do and press down agent with specific immunity.Increase because the danger of skin carcinoma takes place all patients, should come limit exposure under sunlight and ultraviolet by the sunscreen cream of wearing protective clothing or high protection factor.
Immune excessive inhibition can increase the susceptibility that infects, and comprises that opportunistic pathogenesis infects, and causes death to infect and sepsis.
The invention has the advantages that, disintegrating agent adopt add and in add the form that combines, the mycophenolate mofetil dispersible tablet of gained have disintegration time weak point, good dispersing state, medicine stripping rapidly, absorb soon, advantage that bioavailability is high.And taking convenience, both can swallow, chewed, contain and suck, also available water is taken after disperseing, and especially is fit to the old man and the patient of difficulty that swallows.The present invention makes the oral formulations dosage form variation of Mycophenolate Mofetil, provides more choices for clinicist and patient's medication simultaneously.
The specific embodiment
Be embodiments of the invention below, described embodiment just is used for illustrating the present invention, and should not be considered to be limitation of the present invention.
The part material source:
Microcrystalline Cellulose: Zhejiang eyot prospect Pharmaceutical chemistry company limited meets two quality standards of Chinese Pharmacopoeia version in 2000.
Low-substituted hydroxypropyl cellulose: Zhejiang eyot prospect Pharmaceutical chemistry company limited meets two quality standards of Chinese Pharmacopoeia version in 2000.
Polyvinylpolypyrrolidone: international special product company limited meets import drugs registered standard JX20020242.
30 POVIDONE K 30 BP/USP 30: Zhejiang eyot prospect Pharmaceutical chemistry company limited meets two quality standards of Chinese Pharmacopoeia version in 2000.
Magnesium stearate: Zhejiang eyot prospect Pharmaceutical chemistry company limited meets two quality standards of Chinese Pharmacopoeia version in 2000.
Embodiment 1-35
Please refer to the 7th page of table 1 and table 2 to last page.
Carry out factors influencing by embodiment 35, the results are shown in Table 2.
The result shows that mycophenolate mofetil dispersible tablet provided by the invention meets the regulation of Chinese Pharmacopoeia (version in 2000) about dispersible tablet.
The test of embodiment 36 bioequivalences
The main pharmacokinetic parameter C of reference preparation Mycophenolate Mofetil capsule (R) and test preparation mycophenolate mofetil dispersible tablet (A)
Max, T
Max, AUC
0 → 24And AUC
0 → ∞(mean ± standard deviation) is respectively: 20.16 ± 3.47 and 19.88 ± 3.55 μ g/ml; 0.80 ± 0.17 and 0.74 ± 0.19h; 49.96 ± 18.01 and 48.63 ± 16.53 μ g * h/ml; 55.38 ± 18.68 and 54.34 ± 16.63 μ g * h/ml.Test preparation to the relative bioavailability F of reference preparation (with AUC
0 → 24As estimating foundation) be: 99% ± 17% (72%～132%).T
MaxTest through non-engaging in an inspection, and different preparation differences there was no significant differences (U=0.2670, p=0.7895).AUC
0 → 24, AUC
0 → ∞And C
MaxAfter to number conversion, carry out variance analysis, the result shows: both do not have significance meaning (p＞0.05) with the different cycles differences between different preparations.C
Max, AUC
0 → 24And AUC
0 → ∞Two one-side t-assays show that thigh and tlow are all greater than one-side t 0.05.Test preparation AUC
0 → 24And AUC
0 → ∞90% credibility interval all do not exceed the corresponding AUC of reference preparation
0 → 24And AUC
0 → ∞80%～125% scope; The C of test preparation
Max90% credibility interval, do not exceed reference preparation C yet
Max70%～143% scope.Above result shows that the Mycophenolate Mofetil capsule that mycophenolate mofetil dispersible tablet of the present invention is identical with dosage does not have the significance meaning in absorption by human body speed and absorbtivity difference, and two test preparations all have bioequivalence with reference preparation.
More than mycophenolate mofetil dispersible tablet provided by the present invention and preparation method thereof is described in detail, used specific case herein principle of the present invention and embodiment are set forth, the explanation of above embodiment just is used for helping to understand method of the present invention and core concept thereof; Simultaneously, for one of ordinary skill in the art, according to thought of the present invention, the part that all can change in specific embodiments and applications, in sum, this description should not be construed as limitation of the present invention.
Table 1
Continuous table 1
Continuous table 1
Continuous table 1
Continuous table 1
Table 2
Claims (8)
1. a mycophenolate mofetil dispersible tablet is characterized in that, contains the raw material of following weight portion:
Mycophenolate Mofetil 125-500 part
Filler 30-120 part
Disintegrating agent 25-150 part
Sweeting agent 6-24 part
Lubricant 0.5-5 part.
2. mycophenolate mofetil dispersible tablet as claimed in claim 1 is characterized in that: in the described disintegrating agent, add in 20-100 part, 5-50 adds especially.
3. mycophenolate mofetil dispersible tablet as claimed in claim 1 is characterized in that: described filler is selected from a kind of or its combination in lactose, mannitol, starch, pregelatinized Starch, microcrystalline Cellulose, micropowder silica gel, the sucrose.
4. mycophenolate mofetil dispersible tablet as claimed in claim 1 is characterized in that: described disintegrating agent is selected from a kind of or its combination in low-substituted hydroxypropyl cellulose, carboxymethylstach sodium, polyvinylpolypyrrolidone, the crosslinked carboxymethyl fecula sodium.
5. mycophenolate mofetil dispersible tablet as claimed in claim 1 is characterized in that: described sweeting agent is selected from stevioside, Aspartame, glucide and/or xylitol.
6. mycophenolate mofetil dispersible tablet as claimed in claim 1 is characterized in that: described lubricant is selected from magnesium stearate or/and Pulvis Talci.
7. as any described mycophenolate mofetil dispersible tablet in the claim 1 to 6, it is characterized in that described raw material and weight portion thereof are: 250 parts of Mycophenolate Mofetil, 40 parts of microcrystalline Cellulose, 30 parts of polyvinylpolypyrrolidone, 20 parts of low-substituted hydroxypropyl celluloses, 12 parts of steviosides, 2 parts of magnesium stearates.
8. the preparation method of mycophenolate mofetil dispersible tablet as claimed in claim 1 is characterized in that, is made by following steps:
A, each raw material pulverizing is crossed 80 mesh sieves;
B, take by weighing Mycophenolate Mofetil, filler, in the disintegrating agent and the sweeting agent that add, mix homogeneously;
C, adding 5% 30 POVIDONE K 30 BP/USP
30Alcoholic solution system soft material is with 24 mesh sieve system wet granulars;
D, wet granular be in 50 ℃ of dryings, and dry back is with 24 mesh sieve granulate, and even with the disintegrating agent that adds, mix lubricant again, tabletting is packed promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610126992 CN1919184A (en) | 2006-09-18 | 2006-09-18 | Mycophenolate mofetile dispersed tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610126992 CN1919184A (en) | 2006-09-18 | 2006-09-18 | Mycophenolate mofetile dispersed tablet and preparation method thereof |
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ID=37777125
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|---|---|---|---|
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018167628A1 (en) | 2017-03-13 | 2018-09-20 | Ftf Pharma Private Limited | Pharmaceutical composition of oral suspension of immunosuppressive agents |
| CN114569570A (en) * | 2022-03-15 | 2022-06-03 | 浙江长典药物技术开发有限公司 | Mycophenolate mofetil and preparation method thereof |
| US12097284B2 (en) | 2018-08-18 | 2024-09-24 | Liqmeds Worldwide Limited | Mycophenolate oral suspension |
-
2006
- 2006-09-18 CN CN 200610126992 patent/CN1919184A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018167628A1 (en) | 2017-03-13 | 2018-09-20 | Ftf Pharma Private Limited | Pharmaceutical composition of oral suspension of immunosuppressive agents |
| US12097284B2 (en) | 2018-08-18 | 2024-09-24 | Liqmeds Worldwide Limited | Mycophenolate oral suspension |
| US12097285B2 (en) | 2018-08-18 | 2024-09-24 | Liqmeds Worldwide Limited | Mycophenolate oral suspension |
| US12194143B2 (en) | 2018-08-18 | 2025-01-14 | Liqmeds Worldwide Limited | Mycophenolate oral suspension |
| US12226526B2 (en) | 2018-08-18 | 2025-02-18 | Liqmeds Worldwide Limited | Mycophenolate oral suspension |
| CN114569570A (en) * | 2022-03-15 | 2022-06-03 | 浙江长典药物技术开发有限公司 | Mycophenolate mofetil and preparation method thereof |
| CN114569570B (en) * | 2022-03-15 | 2023-03-24 | 浙江长典药物技术开发有限公司 | Mycophenolate mofetil and preparation method thereof |
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