CN107865871B - Tegiloi composition and preparation method thereof - Google Patents
Tegiloi composition and preparation method thereof Download PDFInfo
- Publication number
- CN107865871B CN107865871B CN201710863623.5A CN201710863623A CN107865871B CN 107865871 B CN107865871 B CN 107865871B CN 201710863623 A CN201710863623 A CN 201710863623A CN 107865871 B CN107865871 B CN 107865871B
- Authority
- CN
- China
- Prior art keywords
- parts
- tegafur
- gimeracil
- composition
- filler
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a tegafur and gimeracil composition and a preparation method thereof. Specifically, the invention relates to a composition containing tegafur, gimeracil and oteracil potassium, which comprises the following components in parts by weight: 5 to 50 parts of tegafur, 1 to 20 parts of gimeracil, 5 to 50 parts of oteracil potassium, 10 to 300 parts of filler and 0.1 to 10 parts of lubricant, and is characterized in that the composition does not contain a disintegrating agent or a binder, preferably a disintegrating agent and a binder. The tegafur composition does not contain a disintegrating agent and a binding agent, and can be prepared by adopting a powder mixing and direct filling process. The tegafur composition prepared by the process has the characteristics of rapid dissolution and good stability, and the preparation method is simple to operate and is suitable for industrial production.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a composition containing tegafur, gimeracil and oteracil potassium, which has the characteristics of rapid dissolution and good stability.
Background
Tegafur is a fluorouracil derivative oral anticancer agent, which comprises tegafur (FT) and the following two types of regulators: gimeracil (CDHP) and oteracil (Oxo). The effects of the three components are as follows: FT is a prodrug of 5-Fu, has excellent oral bioavailability, and can be converted into 5-Fu in vivo. CDHP inhibits catabolism of 5-Fu released from FT by dihydropyrimidine dehydrogenase, and contributes to the effective depth of 5-Fu in blood and tumor tissue for a long period of time, thereby achieving a therapeutic effect similar to that of continuous intravenous infusion of 5-Fu. Oxo is capable of blocking phosphorylation of 5-Fu, and after oral administration, Oxo has high distribution concentration in gastrointestinal tissues, thereby influencing the distribution of 5-Fu in gastrointestinal tract and further reducing the toxic effect of 5-Fu. Tegafur has the following advantages compared with 5-Fu: can maintain higher blood concentration and improve anticancer activity; obviously reducing the toxicity of the medicine; the administration is convenient. Currently tegafur is mainly used for the treatment of advanced gastric cancer.
Tegafur is slightly dissolved in water, gimeracil is slightly dissolved in water, oteracil potassium is slightly dissolved in water, but the medicine is required to be quickly dissolved and quickly take effect clinically, so that the medicine is required to be improved to be dissolved by adopting a proper prescription and a proper process in the production of the preparation. Meanwhile, as the tegafur is an alkaline medicament and the gimeracil and the oteracil potassium are acidic medicaments, the stability of the tegafur is reduced to a certain extent by the medicinal composition. Therefore, the dissolution rate and the preparation stability need to be considered when preparing the tegafur and gimeracil and aol capsule.
CN 101574326A discloses a preparation method of tegafur, gimeracil and oteracil potassium capsules, which is characterized in that the capsules contain tegafur micro-pills, gimeracil micro-pills and oteracil potassium micro-pills, although the stability problem of the preparation is solved, the preparation process is more complex and is not suitable for industrial production, the particle sizes and the densities of the three micro-pills are different, and the difference of the filling amount in the capsule filling process is difficult to guarantee.
CN 103816159A discloses a method for preparing tegafur capsules, which comprises the steps of heating and melting poloxamer, dissolving gimeracil in poloxamer melt, granulating with a mixture of tegafur and oteracil potassium, and filling capsules. Although the method solves the problem of dissolution, the preparation process is complex and is not suitable for industrial production.
CN 102302499 a discloses a method for preparing tegafur, which adopts sodium dodecyl sulfate aqueous solution as wetting agent and wet granulation. Although the dissolution problem in vitro is solved, the sodium dodecyl sulfate may promote the absorption of tegafur and gimeracil in vivo, thereby possibly enhancing the toxic and side effects of the medicine.
CN101843621A discloses tegafur hydrochloride granules, which are prepared by a method of preparing cyclodextrin inclusion compounds from active ingredients of drugs, so as to improve the dissolution rate and bioavailability of the drugs, however, the cyclodextrin inclusion process is complicated, and the industrial production in a workshop is inconvenient.
CN101711765A discloses a tegafur dispersible tablet, wherein gimeracil and oteracil potassium can be released in the stomach before tegafur, so that oteracil potassium can better play a role in protecting the gastrointestinal tract, gimeracil can better play a role in coordinating with tegafur, the compliance of patients is improved, but the process adopts a pellet coating technology, and the production process of a workshop is complex.
CN 102614183 a discloses a tegafur oral solid preparation, which adopts a wet granulation process, needs to add additional disintegrating agent and adhesive, and has a complicated process, and the process may cause product instability and poor dissolution.
Therefore, it is necessary to provide a tegafur preparation which has a simple formulation and a simple preparation process and is excellent in preparation stability and dissolution.
Disclosure of Invention
The invention aims to provide a tegafur and gimeracil composition, and the capsule is quick in dissolution, good in preparation stability, simple in preparation process and more suitable for industrialized production.
The invention provides a tegafur composition which comprises the following components in parts by weight: 5 to 50 parts of tegafur, 1 to 20 parts of gimeracil, 5 to 50 parts of oteracil potassium, 10 to 300 parts of filler and 0.1 to 10 parts of lubricant, and is characterized in that the composition does not contain a disintegrating agent or a binder, preferably a disintegrating agent and a binder.
The disintegrant is conventional in the art, and is, for example, one or more selected from crospovidone, croscarmellose sodium, sodium starch glycolate, and low-substituted hydroxypropylcellulose. The adhesive can be one or more selected from high-substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose and polyvidone.
In a preferred embodiment, the composition of the invention is free of surfactant.
Preferably, the composition consists of the following components in parts by weight: 5-50 parts of tegafur, 1-20 parts of gimeracil, 5-50 parts of oteracil potassium, 10-300 parts of a filler and 0.1-10 parts of a lubricant.
In a more preferred embodiment, the composition comprises the following components: 20 parts of tegafur, 5 parts of gimeracil, 19.6 parts of oteracil potassium, 10-300 parts of a filler and 0.1-10 parts of a lubricant.
The filler in the invention can be selected from lactose or sugar alcohols, and the sugar alcohols are preferably one or more of mannitol, xylitol, sorbitol and erythritol.
The lubricant in the present invention is not particularly limited, and a lubricant conventional in the art, such as one or more of magnesium stearate, talc, and silica, may be used.
On the other hand, the invention provides a composition containing tegafur, gimeracil and oteracil potassium, which comprises the following components in parts by weight: 5-50 parts of tegafur, 1-20 parts of gimeracil, 5-50 parts of oteracil potassium, 10-300 parts of filler and 0.1-10 parts of lubricant, wherein the preparation process of the composition comprises the following steps: uniformly mixing tegafur, gimeracil, potassium oteracil and a filler with a lubricant, wherein the mixing is performed without adding a wetting agent. Wherein the wetting agent is water or a mixed solvent of water and ethanol.
The composition of the present invention may be a tablet or capsule. The preparation process also comprises the step of directly tabletting or filling the powder obtained after uniform mixing into capsules.
On the other hand, the invention provides a preparation method of a composition containing tegafur, gimeracil and oteracil potassium, which comprises the following components in parts by weight: 5-50 parts of tegafur, 1-20 parts of gimeracil, 5-50 parts of oteracil potassium, 10-300 parts of filler and 0.1-10 parts of lubricant, wherein the preparation method of the composition comprises the following steps: uniformly mixing tegafur, gimeracil, potassium oteracil and a filler with a lubricant, wherein no solvent is added in the mixing. Wherein the solvent is water or a mixed solvent of water and ethanol.
In a most preferred embodiment, the present invention provides a process for the preparation of a tegafur capsule consisting of: 5-50 parts of tegafur, 1-20 parts of gimeracil, 5-50 parts of oteracil potassium, 10-300 parts of a filler and 0.1-10 parts of a lubricant; wherein the filler is lactose or mannitol; the preparation method of the capsule comprises the steps of uniformly mixing tegafur, gimeracil, potassium oteracil, a filler and a lubricant, and directly filling the mixture into the capsule.
Compared with the prior art, the tegafur and gimeracil Okayama capsule preparation has the following advantages:
(1) the prescription is simple, and the prescription does not contain a surfactant, so that the in-vivo absorption of the medicine is not influenced. The medicine is dissolved out quickly and completely. Meanwhile, the preparation stability is good.
(2) The capsule preparation adopts a process of directly filling the capsule by mixing the powder, has simple preparation process and is very suitable for industrialized production.
Detailed Description
The present invention is further illustrated in detail by the following examples. These examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
Examples 1 to 5
The preparation process comprises the following steps: according to the proportion in the table 1, the raw and auxiliary materials are sieved by a sieve of 80 meshes, are uniformly mixed and are directly filled into capsules to prepare the tegafur and gimerak capsules.
TABLE 1
Comparative examples 1 to 3
The preparation process comprises the following steps: according to the proportion in the table 2, the raw and auxiliary materials are sieved by a sieve of 80 meshes, are uniformly mixed and are directly filled into capsules to prepare the tegafur and gimerak capsules.
TABLE 2
Comparative examples 4 to 7
The preparation process comprises the following steps: according to the proportion in the table 3, the raw and auxiliary materials are sieved by a sieve of 80 meshes, mixed uniformly, then granulated by taking purified water as a wetting agent, dried at 60 ℃, granulated, added with magnesium stearate, mixed uniformly, filled into capsules and prepared into tegafur capsules.
TABLE 3
Examples 1 to 5 and comparative examples 1 to 3: dissolution determination
The dissolution method (second method of 0931 on the general rule of the national pharmacopoeia 2015 edition) is adopted, capsules in examples 1-5 and comparative examples 1-3 are taken, a purified aqueous solution is used as a dissolution medium, the rotating speed is 50 revolutions per minute, the temperature is 37 +/-0.5 ℃, the operation is carried out according to the method, 10ml of dissolution liquid is taken at 15min, the dissolution liquid is filtered by a 0.45 mu m filter membrane, the dissolution rates of tegafur, gimeracil and oteracil potassium in the tegafur capsules are measured by high performance liquid chromatography, the limit is 85% of the marked amount, and the dissolution results are shown in table 4.
TABLE 4
The dissolution test result shows that: in examples 1 to 5 (lactose or sugar alcohols as fillers) the active ingredient has a dissolution rate of more than 85% in 15min, and the dissolution is rapid. In contrast, the dissolution rates of the active ingredients in the comparative examples 1-3 in 15min are all significantly less than 85%, and the dissolution rates are not qualified.
Examples 1 to 5 and comparative examples 4 to 7: investigation of formulation stability
(1) Influence factor test: appropriate amounts of the tegafur capsules of examples 1 to 5 and comparative examples 4 to 7 were placed under intense light irradiation (4500 lx. + -. 500lx) and high temperature (60 ℃ C., high humidity 90%) and sampled and examined on the 5 th and 10 th days, respectively, to find the results shown in Table 5:
TABLE 5
(2) And (3) accelerated test: the tegafur capsules of examples 1 to 5 and comparative examples 4 to 7 were placed in a constant temperature and humidity chamber at 40 ℃ and 75% relative humidity in a commercially available package for 6 months, and samples were taken at the end of 1, 2, 3 and 6 months to examine the relevant substances, and the results are shown in Table 6:
TABLE 6
The influence factor test and the accelerated test result show that related substances of the capsule are basically not obviously changed, which shows that the tegafur and gimeracil Ok capsule preparation prepared by the invention has good stability, and the comparative example has more degraded impurities.
Claims (5)
1. The composition containing tegafur, gimeracil and oteracil potassium is characterized by comprising the following components in parts by weight: 5-50 parts of tegafur, 1-20 parts of gimeracil, 5-50 parts of oteracil potassium, 10-300 parts of filler and 0.1-10 parts of lubricant, wherein the composition is a capsule, and the preparation process of the composition comprises the following steps: uniformly mixing tegafur, gimeracil, oteracil potassium, a filler and a lubricant, and filling the powder obtained after uniform mixing into capsules, wherein the wetting agent is not added in the mixing, and the filler is selected from one or more of lactose, mannitol, xylitol, sorbitol and erythritol.
2. The composition of claim 1, wherein the composition comprises the following components: 20 parts of tegafur, 5 parts of gimeracil, 19.6 parts of oteracil potassium, 10-300 parts of a filler and 0.1-10 parts of a lubricant.
3. A preparation method of a composition containing tegafur, gimeracil and oteracil potassium comprises the following components in parts by weight: 5-50 parts of tegafur, 1-20 parts of gimeracil, 5-50 parts of oteracil potassium, 10-300 parts of filler and 0.1-10 parts of lubricant, wherein the composition is a capsule, and the preparation method of the composition comprises the following steps: uniformly mixing tegafur, gimeracil, oteracil potassium, a filler and a lubricant, and filling the powder obtained after uniform mixing into capsules, wherein the wetting agent is not added in the mixing, and the filler is selected from one or more of lactose, mannitol, xylitol, sorbitol and erythritol.
4. The method of claim 3, wherein the composition comprises the following components: 20 parts of tegafur, 5 parts of gimeracil, 19.6 parts of oteracil potassium, 10-300 parts of a filler and 0.1-10 parts of a lubricant.
5. A preparation method of a tegafur, gimeracil and oteracil potassium capsule comprises the following components: 5-50 parts of tegafur, 1-20 parts of gimeracil, 5-50 parts of oteracil potassium, 10-300 parts of a filler and 0.1-10 parts of a lubricant; wherein the filler is lactose or mannitol; the preparation method of the capsule comprises the steps of uniformly mixing tegafur, gimeracil, potassium oteracil, a filler and a lubricant, and directly filling the mixture into the capsule.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2016108466155 | 2016-09-23 | ||
| CN201610846615 | 2016-09-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107865871A CN107865871A (en) | 2018-04-03 |
| CN107865871B true CN107865871B (en) | 2021-09-03 |
Family
ID=61761232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710863623.5A Active CN107865871B (en) | 2016-09-23 | 2017-09-22 | Tegiloi composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107865871B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009084216A1 (en) * | 2007-12-27 | 2009-07-09 | Taiho Pharmaceutical Co., Ltd. | Oral powder and granular antitumor agent |
| CN102302499A (en) * | 2011-07-12 | 2012-01-04 | 山东新时代药业有限公司 | Capsule preparation containing tegafur, gimeracil and potassium oxonate |
| CN103142607A (en) * | 2013-04-10 | 2013-06-12 | 山东新时代药业有限公司 | Preparation method of tegafur gimeracil oteracil potassium capsule |
| CN103816159A (en) * | 2014-03-20 | 2014-05-28 | 山东新时代药业有限公司 | Tegafur gimeracil oteracil potassium capsule and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG194922A1 (en) * | 2011-05-25 | 2013-12-30 | Taiho Pharmaceutical Co Ltd | Dry-coated tablet containing tegafur, gimeracil and oteracil potassium |
-
2017
- 2017-09-22 CN CN201710863623.5A patent/CN107865871B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009084216A1 (en) * | 2007-12-27 | 2009-07-09 | Taiho Pharmaceutical Co., Ltd. | Oral powder and granular antitumor agent |
| CN102302499A (en) * | 2011-07-12 | 2012-01-04 | 山东新时代药业有限公司 | Capsule preparation containing tegafur, gimeracil and potassium oxonate |
| CN103142607A (en) * | 2013-04-10 | 2013-06-12 | 山东新时代药业有限公司 | Preparation method of tegafur gimeracil oteracil potassium capsule |
| CN103816159A (en) * | 2014-03-20 | 2014-05-28 | 山东新时代药业有限公司 | Tegafur gimeracil oteracil potassium capsule and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 替吉奥胶囊处方优选;戚苏明 等;《中国药业》;20061231;第15卷(第11期);第44-45页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107865871A (en) | 2018-04-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6560289B2 (en) | New pharmaceutical composition | |
| JP5775464B2 (en) | Delayed release oral dosage composition containing amorphous CDDO-ME | |
| JP5794650B2 (en) | Solubility improving preparation for poorly soluble drugs | |
| KR101977785B1 (en) | Composite formulation for oral administration comprising ezetimibe and rosuvastatin and a process for the preparation thereof | |
| TW202112376A (en) | Oral solid tablet comprising bruton's tyrosine kinase inhibitor and preparation method therefor | |
| CN107812195B (en) | Stable pharmaceutical composition of (6S) -5-methyl-tetrahydrofolate calcium salt | |
| JP2011500548A (en) | Dibotentan composition comprising mannitol and / or microcrystalline cellulose | |
| ES2414384T3 (en) | Modified release composition comprising ranolazine | |
| EP3148513B1 (en) | Ceritinib formulation | |
| JP2015054851A (en) | Coated oral solid preparation | |
| CN107865871B (en) | Tegiloi composition and preparation method thereof | |
| CN102068415B (en) | Carbazole sulfonamide anti-tumor medicine dispersible tablets and preparation method thereof | |
| CN106619646B (en) | A kind of preparation method of tegafur, gimeracil and oteracil potassium composition | |
| JP2020518611A (en) | Compositions with improved water solubility and bioavailability | |
| CN106913537B (en) | Abiraterone acetate sublingual tablet and preparation method thereof | |
| WO2020111089A1 (en) | Pharmaceutical composition | |
| CN111617048A (en) | Erlotinib sustained-release preparation for treating non-small cell lung cancer | |
| JP2010001242A (en) | Rebamipide solid preparation, and method for producing the same | |
| JP2020176090A (en) | Method for Producing Solid Formulation Containing Dasatinib Anhydride | |
| KR102363727B1 (en) | Composition for preparing solid formulation containing pranlukast having enhanced bioavailability and production method thereof | |
| TWI746418B (en) | Pharmaceutical dosage forms comprising sodium 1-[6-(morpholin-4-yl)pyrimidin-4-yl]-4-(1h-1,2,3-triazol-1-yl)-1h-pyrazol-5-olate | |
| CN113893222B (en) | Pharmaceutical composition and preparation method and application thereof | |
| CN114716417B (en) | Bulk drug of compound and fumaric acid in crystal form, pharmaceutical composition and application thereof | |
| CN106420759B (en) | A kind of preparation method of tegafur, gimeracil and oteracil potassium composition | |
| JP7492370B2 (en) | Fingolimod hydrochloride-containing preparation and method for producing the preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |