CN115429797A - Composition containing oxygen clopidogrel or salts thereof and preparation thereof - Google Patents
Composition containing oxygen clopidogrel or salts thereof and preparation thereof Download PDFInfo
- Publication number
- CN115429797A CN115429797A CN202211051927.9A CN202211051927A CN115429797A CN 115429797 A CN115429797 A CN 115429797A CN 202211051927 A CN202211051927 A CN 202211051927A CN 115429797 A CN115429797 A CN 115429797A
- Authority
- CN
- China
- Prior art keywords
- oxygen
- clopidogrel
- containing clopidogrel
- composition
- isomer
- 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.)
- Pending
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
- A61K31/435—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a composition for preventing or treating side effects in the aspect of digestive tract caused by anticoagulant and a preparation method thereof, in particular to a pharmaceutical composition containing (7 aS,2' S) -2-oxy-clopidogrel or salts and derivatives thereof and a preparation method thereof. The pharmaceutical composition provided by the invention has stable property, and can effectively improve gastrointestinal side effects such as dyspepsia caused by long-term administration of (7aS,2' S) -2-O-clopidogrel.
Description
Technical Field
The invention relates to the technical field of medicines, and particularly relates to a pharmaceutical composition containing (7 aS,2' S) -2-oxy-clopidogrel or a salt thereof and a preparation method thereof.
Background
(7 aS,2' S) -2-oxy-clopidogrel (the following compound A) is a metabolite of clopidogrel in a human body, and has a chemical name: (S) -methyl 2- (2-chlorophenyl) -2- ((S) -2-oxo-2, 6,7 a-tetrahydrothiophene [3,2-c ] bipyridin-5 (4H) -yl) acetate:
like clopidogrel, the compound A can be further metabolized and activated in a human body to form an active metabolite H4 capable of inhibiting platelet aggregation, and then the combination of Adenosine Diphosphate (ADP) and a platelet P2Y12 receptor thereof and the activation of a secondary ADP-mediated glycoprotein GPIIb/IIIa compound are selectively inhibited, so that the effect of inhibiting platelet aggregation is achieved. Recent studies have shown that in long-term administration tests, adverse reactions of the digestive gastrointestinal tract, including gastrointestinal hemorrhage, dyspepsia, gastrointestinal inflammatory reactions, etc., occur due to the risk of bleeding of high doses of compound a. Therefore, in order to improve the safety of the medicine, control the quality of the medicine and ensure the effectiveness of the medicine, the problem to be solved clinically in the field is solved urgently.
Disclosure of Invention
In view of the above, in order to solve at least one of the above technical problems, the present invention provides a pharmaceutical composition containing (7 aS, 2's) -2-oxo-clopidogrel (hereinafter, referred to aS "compound a") and a preparation method thereof, and the pharmaceutical composition provided by the present invention has few adverse reactions, stable properties, and is suitable for clinical needs.
The invention provides a pharmaceutical composition, which comprises a compound A or a salt and a derivative thereof, wherein the derivative comprises one or more of oxygen-containing clopidogrel oxide, oxygen-containing clopidogrel isomer Z2, oxygen-containing clopidogrel isomer Z3, oxygen-containing clopidogrel isomer Z4 and oxygen-containing clopidogrel enolate.
The above derivatives have the following structures:
further, the above composition comprises compound a or a salt thereof and a derivative thereof comprising an oxypidogrel enolate.
Further, the derivative also comprises one or more of oxygen-containing clopidogrel oxide, oxygen-containing clopidogrel isomer Z2, oxygen-containing clopidogrel isomer Z3 and oxygen-containing clopidogrel isomer Z4; preferably, the above derivatives comprise oxygen-containing clopidogrel oxides, oxygen-containing clopidogrel isomers Z2 and oxygen-containing clopidogrel enolates.
Further, the amount of compound a or a salt thereof in the above composition is not less than 97wt%; preferably not less than 98.5wt%; or/and the amount of derivative in the composition does not exceed 3wt%; preferably not more than 1.5wt%.
Further, the composition comprises the following substances by weight: the compound A or the salt thereof is not less than 97wt%, and the oxygen-containing clopidogrel enolate is not more than 0.5wt%.
Preferably, the above composition comprises the following materials by weight: the compound A or its salt is not less than 98.5wt%, and the oxygen-containing clopidogrel enolate is not more than 0.2wt%.
More preferably, the above composition comprises the following materials by weight: the compound A or the salt thereof is not less than 98.5wt%, and the oxygen-containing clopidogrel enolate is not more than 0.1wt%.
Most preferably, the above composition comprises by weight: the compound A or the salt thereof is not less than 98.5wt%, and the oxygen-containing clopidogrel enolate is 0.1-0.2 wt%.
Further, the composition also comprises any one or more of the following substances by weight: oxygen-containing clopidogrel oxide is not more than 0.5wt%, oxygen-containing clopidogrel isomer Z2 is not more than 2.0wt%, oxygen-containing clopidogrel isomer Z3 is not more than 0.5wt%, and oxygen-containing clopidogrel isomer Z4 is not more than 0.5wt%; preferably, the above composition further comprises the following materials by weight: oxygen-containing clopidogrel oxide is not more than 0.5wt% and oxygen-containing clopidogrel isomer Z2 is not more than 2.0wt%.
Preferably, the composition further comprises any one or more of the following substances by weight: oxygen-containing clopidogrel oxide is not more than 0.1wt%, oxygen-containing clopidogrel isomer Z2 is not more than 1.0wt%, oxygen-containing clopidogrel isomer Z3 is not more than 0.1wt%, and oxygen-containing clopidogrel isomer Z4 is not more than 0.1wt%; preferably, the above composition further comprises the following materials by weight: oxygen-containing clopidogrel oxide is not more than 0.1wt% and oxygen-containing clopidogrel isomer Z2 is not more than 1.0wt%.
Further, the composition comprises the following substances by weight: the compound A or its salt is not less than 97wt%, oxygen-containing clopidogrel oxide is not more than 0.5wt%, oxygen-containing clopidogrel isomer Z2 is not more than 2.0wt%, and oxygen-containing clopidogrel enolate is not more than 0.5wt%.
Preferably, the above composition comprises the following materials by weight: the compound A or its salt is not less than 98.5wt%, oxygen-containing clopidogrel oxide is not more than 0.1wt%, oxygen-containing clopidogrel isomer Z2 is not more than 1.0wt%, and oxygen-containing clopidogrel enolate is not more than 0.1wt%.
Further, the composition also comprises any one or two of the following substances by weight: oxygen-containing clopidogrel isomer Z3 is not more than 0.5wt%, and oxygen-containing clopidogrel isomer Z4 is not more than 0.5wt%.
Preferably, the above composition further comprises any one or two of the following by weight: oxygen-containing clopidogrel isomer Z3 is not more than 0.1wt%, and oxygen-containing clopidogrel isomer Z4 is not more than 0.1wt%.
Further, the composition comprises the following substances in parts by weight:
compound a or a salt thereof: 97.0 to 99.9 portions;
oxygen-containing clopidogrel enolate: 0.01 to 0.5 portion.
Preferably, the composition comprises the following substances in parts by weight:
compound a or a salt thereof: 98.5 to 99.9 portions;
oxygen-containing clopidogrel enolate: 0.01 to 0.2 portion.
More preferably, the above composition comprises the following materials in parts by weight:
compound a or a salt thereof: 98.5 to 99.9 portions;
clopidogrel oxoenolate: 0.01 to 0.1 portion.
Most preferably, the above composition comprises the following materials in parts by weight:
compound a or a salt thereof: 98.5-99.9 parts;
clopidogrel oxoenolate: 0.1 to 0.2 portion.
Further, the composition also comprises any one or more of the following substances in parts by weight:
oxygen-containing clopidogrel oxide: 0.01 to 0.5 portion;
oxygenated clopidogrel isomer Z2:0.01 to 2.0 portions;
oxygenated clopidogrel isomer Z3:0.01 to 0.5 portion;
oxygen-containing clopidogrel isomer Z4:0.01 to 0.5 portion.
Preferably, the composition further comprises any one or more of the following substances in parts by weight:
oxygen-containing clopidogrel oxide: 0.01 to 0.1 portion;
oxygenated clopidogrel isomer Z2:0.01 to 1.0 portion;
oxygen-containing clopidogrel isomer Z3:0.01 to 0.1 portion;
oxygen-containing clopidogrel isomer Z4:0.01 to 0.1 portion.
Further, the composition comprises the following substances in parts by weight:
compound a or a salt thereof: 97.0 to 99.9 portions;
oxygen-containing clopidogrel oxide: 0.01 to 0.5 portion;
oxygen-containing clopidogrel isomer Z2:0.01 to 2.0 portions;
clopidogrel oxoenolate: 0.01 to 0.5 portion.
Preferably, the above composition comprises the following materials in parts by weight:
compound a or a salt thereof: 98.5-99.9 parts;
oxygen-containing clopidogrel oxide: 0.01 to 0.1 portion;
oxygen-containing clopidogrel isomer Z2:0.01 to 1.0 portion;
oxygen-containing clopidogrel enolate: 0.01 to 0.1 portion.
Further, the composition also comprises any one or two of the following substances in parts by weight:
oxygenated clopidogrel isomer Z3:0.01 to 0.5 portion;
oxygen-containing clopidogrel isomer Z4:0.01 to 0.5 portion.
Preferably, the composition further comprises any one or two of the following substances in parts by weight:
oxygenated clopidogrel isomer Z3:0.01 to 0.1 portion;
oxygen-containing clopidogrel isomer Z4:0.01 to 0.1 portion.
Further, the present invention also provides a pharmaceutical formulation comprising any one of the pharmaceutical compositions described above and a pharmaceutically acceptable carrier.
Further, the above pharmaceutical preparation is selected from a tablet, a capsule or a granule.
Further, the pharmaceutically acceptable carrier includes: one or more of lubricant, disintegrant and diluent.
Preferably, the diluent includes, but is not limited to, any one or more of mannitol, microcrystalline cellulose, lactose, starch, pregelatinized starch, powdered sugar, dextrin, and inorganic salts.
Preferably, the disintegrating agent includes, but is not limited to, any one or more of low-substituted hydroxypropyl cellulose, crospovidone, croscarmellose sodium, carboxymethyl starch sodium and dry starch.
Preferably, the lubricant comprises any one or more of magnesium stearate, sodium stearyl fumarate, talcum powder, polyethylene glycol and hydrogenated vegetable oil.
Further, the invention also provides a preparation method of the pharmaceutical preparation, which comprises the following steps: weighing the composition according to the prescription amount, adding the pharmaceutically acceptable carrier according to the prescription amount, uniformly mixing, and pressing into tablets or filling capsules or preparing into granules.
Further, the salt of the above compound a includes pharmaceutically acceptable inorganic salts or organic salts.
Preferably, the salt of compound a includes, but is not limited to, hydrochloride, sulfate, bisulfate and other pharmaceutically acceptable salts.
Further, the above "pharmaceutically acceptable carrier" refers to a diluent, adjuvant, excipient, or vehicle with which the active ingredient is administered and which is, within the scope of sound medical judgment, suitable for contact with the tissues of humans and/or other animals without excessive toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit/risk ratio.
Advantageous effects: the invention provides a composition of (7 aS,2 'S) -2-oxy-clopidogrel or salt and derivative thereof for the first time, which unexpectedly reduces or treats gastrointestinal dyspepsia side reaction caused by long-term use of (7 aS,2' S) -2-oxy-clopidogrelThe obtained product has less adverse reaction and stable property, and can meet more clinical requirements.
Detailed Description
The scheme of the present invention will be explained below with reference to experimental examples and examples. It will be appreciated by those skilled in the art that the following examples are illustrative only and should not be taken as limiting the scope of the invention. The particular techniques or conditions not specified in the examples are performed according to the techniques or conditions described in the literature in the field or according to the product specifications. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products obtained commercially.
Sources of materials
The compound A, the compound A bisulfate, the oxygen-containing clopidogrel isomer Z2, the oxygen-containing clopidogrel isomer Z3, the oxygen-containing clopidogrel isomer Z4 and the oxygen-containing clopidogrel enolate have the pharmaceutical purity of 99.9 percent, are synthesized by the Doudoshukang biological medicine science and technology company according to the prior art, and do not contain other substances (for example, the compound A and the salt thereof do not contain the derivative).
Experimental example 1 Effect of continuous administration of drugs to rats on general Condition and food intake
1. Purpose of the test
The influence of the drug on the general state and food intake of rats after the continuous gavage administration of the rats for 14 days under the condition of equimolar dose is considered, and the prevention and/or treatment effect of each pharmaceutical composition on gastrointestinal adverse reactions caused by the compound A is further indirectly evaluated.
Capsule wall testing and preparation thereof
Example 1:
(1) Sample composition: 98.5mg of the compound A, 1.0mg of oxygen-containing clopidogrel oxide, 2.0mg of oxygen-containing clopidogrel isomer Z2 and 0.1mg of oxygen-containing clopidogrel enolate.
(2) Sample treatment: putting the materials into a clean administration container, adding a proper amount of Solutol for dissolving, carrying out spiral oscillation, adding pure water, carrying out ultrasonic treatment, and carrying out spiral oscillation until the compound is completely dissolved (for use in preparation).
Examples 2 to 18 and comparative examples 1 to 4:
the sample compositions of examples 2 to 17 are shown in Table 1, and the sample treatment method is the same as that of example 1.
Example 18: compound A is its hydrogen sulfate salt and is weighed as compound A, otherwise the same as in example 4.
Comparative example 1: a sample of the composition prepared in accordance with CN111150731A, example 12, was processed in the same manner as in example 1.
Comparative example 2: the API samples in the table on page 17 of WO2021070200A2 were processed as in example 1.
Comparative example 3: a sample of Compound A bisulfate prepared according to CN 10424707A example 3 was treated in the same manner as in example 1.
Comparative example 4: the sample (drug) consisted of compound a only and was processed in the same manner as in example 1.
\9354
The above dose of administration: calculated as compound a. The multiple gavage dosing schedule for the groups of examples 2-18 and comparative examples 1-4 was the same as for the group of example 1.
\9355
The SD rats are male and female simultaneously and are randomly grouped into 10 rats each group; the effect of the drug on the general condition and food intake of the rats was observed and recorded after 14 consecutive days, once a day, with the corresponding drug or saline administered by gavage.
\9356
(1) In the general state study of rats 14 days after continuous gavage administration in each group, more than half of the rats in the example 1 group, the example 10 group, the example 15 group and the comparative examples 1 to 4 have hair erection, hypomotility and abdominal distension; no exception was found in the remaining example groups.
(2) The results of observing food intake of rats 14 days after continuous gavage administration in each group are shown in Table 3.
Description of the invention: * P<0.01 vs blank group; ▲▲ p < 0.01 vs. comparative example 4.
As seen from Table 3, compared with the blank group, the rats of examples 2-9, 11-14 and 16-18 had food intake within 24 hours after the last administration substantially identical to that of the blank group, and had no statistical difference; in particular, examples 4, 5, 7, 8, 13, 14, 18 are relatively closer together. Compared with the group of the comparative example 4, the rats in the groups of the examples 2 to 9, 11 to 14 and 16 to 18 have very significant improvement of food intake within 24 hours after the last administration compared with the group of the comparative example 4, and have statistical difference (P < 0.01). On the other hand, the rats in the example 1 group, the example 10 group, the example 15 group and the comparative examples 1 to 4 had a very significant decrease in food consumption within 24 hours after the last administration compared with the blank group and had a statistical difference (P < 0.01).
The above results show that the composition has an unexpected improvement in the side effect of dyspepsia in the treatment of compound a when the amount of compound a or its salt is 97% or more and the amount of the compound a derivative is not more than 3%. Specifically, when the derivative in the composition is an oxygen-containing clopidogrel enolate and the content is not more than 0.5 percent, the composition has the effect of remarkably improving the side effect of dyspepsia; when the derivative simultaneously contains oxygen-containing clopidogrel oxide, oxygen-containing clopidogrel isomer Z2 and oxygen-containing clopidogrel enolate, and the dosage of the oxygen-containing clopidogrel oxide is not more than 0.5 percent, the dosage of the oxygen-containing clopidogrel isomer Z2 is not more than 2.0 percent, and the dosage of the oxygen-containing clopidogrel enolate is not more than 0.5 percent, the effect of obviously improving the dyspepsia side effect is better; especially, when the dosage of the oxygen-containing clopidogrel oxide is not more than 0.1%, the dosage of the oxygen-containing clopidogrel isomer Z2 is not more than 1.0%, and the dosage of the oxygen-containing clopidogrel enolate is not more than 0.1%, the pharmaceutical composition has the best effect of treating dyspepsia, and basically achieves the effect of completely curing dyspepsia side effects or the effect of completely avoiding the dyspepsia side effects of the compound A. When the amount of the derivatives exceeds the range, for example, the amount of the oxygen-containing clopidogrel oxide exceeds 0.5% (example 1 is about 1%), the amount of the oxygen-containing clopidogrel isomer Z2 exceeds 2% (example 10 is about 3%), or the amount of the oxygen-containing clopidogrel enolate exceeds 0.5% (example 15 is about 1%), the food consumption is remarkably reduced, and obvious digestive adverse reactions occur. In addition, when the composition of the present invention further comprises any one or more other derivatives, including but not limited to oxygen-containing clopidogrel isomer Z3, oxygen-containing clopidogrel isomer Z4, formula IIB in CN111150731A, and other impurities mentioned in patent WO2021070200A2, the efficacy of the above composition is not affected. That is, when the pharmaceutical composition of the present invention contains an oxygenated clopidogrel enolate, the kind of other derivatives does not affect the therapeutic and ameliorating effects of the composition of the present invention on dyspepsia, and the effect is the best when the composition contains an oxygenated clopidogrel enolate, an oxygenated clopidogrel isomer Z2, and an oxygenated clopidogrel oxide at the same time.
Experimental example 2: study of pharmaceutical stability
1. Tablet preparation
(1) Prescription: examples 19 to 25 are shown in Table 4.
Remarking: (1) In the formulas of example 19 and example 25, the compound A was prepared as compound A sample (batch numbers: 39201, 39209, respectively) from Doudosbeck biomedical science and technology Ltd, wherein the content of the compound A was 98.0%. (2) The amount of compound a bisulphate salt of example 23 is calculated as compound a.
(2) The preparation process comprises the following steps: a) Weighing raw and auxiliary materials, premixing the compound A composition and mannitol accounting for 30% of the total amount, uniformly mixing a mixture of the compound A composition and the mannitol, the rest mannitol, microcrystalline cellulose, pregelatinized starch and croscarmellose sodium, and then adding sodium stearyl fumarate to be uniformly mixed; b) And tabletting the uniformly mixed mixture by using a tabletting machine.
Consideration of the stability of the Components of the Tunnel
(1) The investigation method comprises the following steps: the tablets of examples 19 to 25 were left to stand in a high humidity environment (high temperature 25 ℃ C., high humidity 92.5%) for 10 days, and the content and the change of substances on the 0 th and 10 th days of each preparation were examined.
(2) And (4) investigation results: the results of 0-day and 10-day high humidity examinations of examples 19 to 25 are shown in tables 5 and 6.
The above experimental results show that after 10 days of investigation under a high-humidity environment, the content of the compound A changes within 0.6% in 10 days compared with 0 days, which indicates that the content is stable; the number of related substances is unchanged, and the absolute value of the change of the derivative and the total impurity content of the compound is below 0.10%, indicating that the derivative and the impurity are stable. Therefore, the pharmaceutical preparation has safe and reliable quality and is suitable for clinical medication.
The above description is only a preferred embodiment of the present invention, and it should be noted that various modifications to these embodiments can be implemented by those skilled in the art without departing from the technical principle of the present invention, and these modifications should be construed as the scope of the present invention.
Claims (10)
1. A pharmaceutical composition comprising compound a or a salt thereof and a derivative thereof, said derivative comprising an oxoclopidogrel enolate.
2. The composition of claim 1, wherein the derivative further comprises one or more of an oxygenated clopidogrel oxide, an oxygenated clopidogrel isomer Z2, an oxygenated clopidogrel isomer Z3, an oxygenated clopidogrel isomer Z4; preferably, the derivatives comprise an oxygen-containing clopidogrel oxide, an oxygen-containing clopidogrel isomer Z2, and an oxygen-containing clopidogrel enolate.
3. The composition according to any one of claims 1 to 2, wherein the amount of compound a or a salt thereof in the composition is not less than 97wt%; preferably not less than 98.5wt%; or/and the amount of derivative in the composition does not exceed 3wt%; preferably not more than 1.5wt%.
4. A composition according to any one of claims 1 to 3, characterized in that it comprises the following by weight: the compound A or its salt is not less than 97wt%, and the oxygen-containing clopidogrel enolate is not more than 0.5wt%.
5. The composition of claim 4, further comprising any one or more of the following by weight: oxygen-containing clopidogrel oxide is not more than 0.5wt%, oxygen-containing clopidogrel isomer Z2 is not more than 2.0wt%, oxygen-containing clopidogrel isomer Z3 is not more than 0.5wt%, and oxygen-containing clopidogrel isomer Z4 is not more than 0.5wt%; preferably, the composition further comprises the following materials by weight: oxygen-containing clopidogrel oxide is not more than 0.5wt% and oxygen-containing clopidogrel isomer Z2 is not more than 2.0wt%.
6. The composition according to any one of claims 1 to 5, characterized in that it comprises, in parts by weight:
compound a or a salt thereof: 97.0 to 99.9 portions;
oxygen-containing clopidogrel enolate: 0.01 to 0.5 portion.
7. The composition of claim 6, further comprising any one or more of the following in parts by weight:
oxygen-containing clopidogrel oxide: 0.01 to 0.5 portion;
oxygenated clopidogrel isomer Z2:0.01 to 2.0 portions;
oxygen-containing clopidogrel isomer Z3:0.01 to 0.5 portion;
oxygen-containing clopidogrel isomer Z4:0.01 to 0.5 portion; preferably, the composition further comprises the following materials in parts by weight:
oxygen-containing clopidogrel oxide: 0.01 to 0.5 portion;
oxygen-containing clopidogrel isomer Z2:0.01 to 2.0 portions.
8. A pharmaceutical formulation comprising the pharmaceutical composition of any one of claims 1 to 7 and a pharmaceutically acceptable carrier.
9. The pharmaceutical formulation of claim 8, wherein the pharmaceutical formulation is selected from a tablet, capsule or granule; preferably, the pharmaceutically acceptable carrier comprises one or more of a lubricant, a disintegrant, and a diluent.
10. A process for preparing a pharmaceutical formulation according to any one of claims 8 to 9, comprising the steps of: weighing the composition according to the prescription, adding the pharmaceutically acceptable carrier according to the prescription, uniformly mixing, and pressing into tablets or filling into capsules or preparing into granules.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211051927.9A CN115429797A (en) | 2022-08-31 | 2022-08-31 | Composition containing oxygen clopidogrel or salts thereof and preparation thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211051927.9A CN115429797A (en) | 2022-08-31 | 2022-08-31 | Composition containing oxygen clopidogrel or salts thereof and preparation thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115429797A true CN115429797A (en) | 2022-12-06 |
Family
ID=84244906
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211051927.9A Pending CN115429797A (en) | 2022-08-31 | 2022-08-31 | Composition containing oxygen clopidogrel or salts thereof and preparation thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115429797A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104245707A (en) * | 2011-06-27 | 2014-12-24 | Ipca实验室有限公司 | Anti-thrombotic compounds |
| CN108685913A (en) * | 2018-07-31 | 2018-10-23 | 成都施贝康生物医药科技有限公司 | The composition and preparation method and application of oxygen-containing pyrrole Gray optical isomer or its salt |
| CN111150731A (en) * | 2020-01-19 | 2020-05-15 | 成都施贝康生物医药科技有限公司 | Composition containing oxirangol optical isomer or salt thereof and application |
| CN111166745A (en) * | 2020-01-19 | 2020-05-19 | 成都施贝康生物医药科技有限公司 | Composition containing racemic oxypyramine or salt thereof and application |
-
2022
- 2022-08-31 CN CN202211051927.9A patent/CN115429797A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104245707A (en) * | 2011-06-27 | 2014-12-24 | Ipca实验室有限公司 | Anti-thrombotic compounds |
| CN108685913A (en) * | 2018-07-31 | 2018-10-23 | 成都施贝康生物医药科技有限公司 | The composition and preparation method and application of oxygen-containing pyrrole Gray optical isomer or its salt |
| CN111150731A (en) * | 2020-01-19 | 2020-05-15 | 成都施贝康生物医药科技有限公司 | Composition containing oxirangol optical isomer or salt thereof and application |
| CN111166745A (en) * | 2020-01-19 | 2020-05-19 | 成都施贝康生物医药科技有限公司 | Composition containing racemic oxypyramine or salt thereof and application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8753679B2 (en) | Capsule formulation of pirfenidone and pharmaceutically acceptable excipients | |
| JP3810079B2 (en) | Composition containing micronized nebivolol | |
| FI101040B (en) | A process for the preparation of an oral dosage form for the treatment of central dopamine deficiency states | |
| SE453797B (en) | THERAPEUTIC, SOLID UNIT DOSAGE FORM WITH EXTENDED DISPOSAL SAMPLES WHERE BERARM MATERIALS INCLUDE HYDROXYPROPYLMETHYL CELLULOSA WITH HIGH MOLECULES WEIGHT | |
| JPS6253920A (en) | Medicine | |
| CN101069675A (en) | A method of alleviating signs and symptons of spasticity | |
| CA2182004C (en) | Film coated tablet of paracetamol and domperidone | |
| CN107812195B (en) | Stable pharmaceutical composition of (6S) -5-methyl-tetrahydrofolate calcium salt | |
| EP3744320A1 (en) | Pharmaceutical tablet composition comprising edoxaban | |
| US20020143058A1 (en) | Process for preparing non-hygroscopic sodium valproate composition | |
| EP4054537B1 (en) | Oral formulation of x842 | |
| JP6476331B2 (en) | Anti-tuberculosis stable pharmaceutical composition in the form of dispersible tablets containing isoniazid granules and rifapentine granules and a process for producing the same | |
| JP5318400B2 (en) | Tablets containing levofloxacin | |
| AU741201B2 (en) | 8-chloro-6,11-dihydro-11-(4-piperidylidene)-5H-benzo(5,6) cyclohepta (1,2-b)pyridine oral compositions | |
| KR20160012706A (en) | Sustained release formulations | |
| CN115429797A (en) | Composition containing oxygen clopidogrel or salts thereof and preparation thereof | |
| CA3198489A1 (en) | Rapidly infusing cannabinoid compositions, processes of manufacture, and methods of use | |
| CN113214065B (en) | Gossypol crystal III substance, preparation method, composition and application thereof | |
| AU2013201986B2 (en) | Capsule Formulation Of Pirfenidone And Pharmaceutically Acceptable Excipients | |
| CN114053282A (en) | Application of tormentic acid and anisodamine capsule in preparing medicament for treating diabetes | |
| EP4267110A1 (en) | Stable prolonged release formulation of vitamin c and a process for preparation thereof | |
| AU2022331317A1 (en) | IMMEDIATE RELEASE FORMULATIONS OF d-LYSERGIC ACID DIETHYLAMIDE FOR THERAPEUTIC APPLICATIONS | |
| WO2024085821A1 (en) | Content uniformity of teriflunomid in pharmaceutical dosage forms | |
| KR20160034983A (en) | Anti-tuberculosis stable pharmaceutical composition in a form of a dispersible tablet comprising granules of isoniazid and granules of rifapentine and its process of preparation | |
| HUE029193T2 (en) | Sustained release pharmaceutical formulations of Thiocolchicoside |
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 |