CN112438948A - Phloroglucinol composition and preparation method thereof - Google Patents
Phloroglucinol composition and preparation method thereof Download PDFInfo
- Publication number
- CN112438948A CN112438948A CN201910832085.2A CN201910832085A CN112438948A CN 112438948 A CN112438948 A CN 112438948A CN 201910832085 A CN201910832085 A CN 201910832085A CN 112438948 A CN112438948 A CN 112438948A
- Authority
- CN
- China
- Prior art keywords
- phloroglucinol
- trihydroxybenzoic acid
- content
- stabilizer
- composition
- 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.)
- Withdrawn
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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a phloroglucinol composition and a preparation method thereof. A phloroglucinol composition is an aqueous solution of phloroglucinol and 1,3, 5-trimethoxybenzene, wherein the content of phloroglucinol is 9-11 mg/ml, the content of 1,3, 5-trimethoxybenzene is 9-11 mu g/ml, and the phloroglucinol composition contains trihydroxybenzoic acid isomer (OH)3C6H2COOH acts as a stabilizer. The phloroglucinol composition provided by the invention has good stability, and reduces the risk of drug interaction by removing the stabilizer, the pH regulator and the osmotic pressure regulator without adding other components, wherein the stabilizer reduces the oxidative degradation of phloroglucinol and effectively overcomes the defect of poor stability of the prior phloroglucinol product. In addition, the invention provides a chamberThe preparation method of the phloroglucinol composition is simple and feasible, the process is controllable, and the industrial operability is strong, so that a good foundation is laid for developing phloroglucinol injection.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a phloroglucinol composition and a preparation method thereof.
Background
The phloroglucinol is a myotropic, non-atropine and non-papaverine smooth muscle spasmolytic, is widely applied to treating diseases caused by smooth muscle spasm, can directly act on the smooth muscles of gastrointestinal tract, biliary tract and urinary tract to relieve the spasmodic pain of the smooth muscle, has quick spasmolytic effect, does not have any atropine-like adverse reaction, has excellent tolerance of patients, and is applied in Europe and America for more than 60 years, thereby becoming a first choice medicament for the spasmolysis treatment of European women. Is clinically applicable to acute spastic pain caused by dysfunction of the digestive system and biliary tract; acute spasmodic urinary tract, bladder, renal colic; and gynecological spasmodic pain.
Pain caused by smooth muscle spasm is one of the most common clinical emergencies. The pain may occur in urinary system, digestive system, reproductive system, etc. with smooth muscle widely distributed, such as renal colic, biliary colic, gastrointestinal spasm, gynecological spastic pain, etc. The main drugs clinically used for relieving spastic pain: anticholinergic drugs, central analgesics. Anticholinergic drugs (such as atropine) have certain curative effect, but the patients have obvious side effects of dry mouth, flushing, mydriasis, dizziness, palpitation, blurred vision, urinary retention and the like, and are not suitable for the elderly patients who are easy to cause urinary retention, glaucoma and the like. Central analgesic drugs (such as morphine, dolantin and the like) have remarkable analgesic effect, but are easy to addiction after being repeatedly used, and are easy to cover certain acute diseases needing surgical treatment, so that misdiagnosis is caused, and therefore, the central analgesic drugs are not used as preferred drugs.
However, phloroglucinol is easy to oxidize and is sensitive to light because the structure of phloroglucinol contains three phenolic hydroxyl groups, so that the stability of the aqueous solution containing phloroglucinol is relatively poor.
In the current literature, the means to solve the above technical problems is often to introduce antioxidants or stabilizers into the formulation. For example, in patent CN 104323986A, an antioxidant sodium metabisulfite and a cosolvent propylene glycol are introduced to increase the stability of a phloroglucinol aqueous solution, the sodium metabisulfite may be ionized under an acidic condition to interact with a main drug, the central neurotoxicity risk of an organic solvent propylene glycol is high, and the safety of the drug under the prescription needs to be researched; patent CN106539753A finds the stabilizing effect of sorbitol on phloroglucinol aqueous solution, but sorbitol has the limitation of higher risk for patients with renal insufficiency and cardiac insufficiency; in patent CN 104490799A, phloroglucinol, tween 80 and lactose are dissolved in water for injection, and freeze-dried to prepare a freeze-dried preparation with good re-solubility, tween 80 used in the method may have hemolysis risk, and is not recommended to be used for intravenous injection.
Disclosure of Invention
The invention provides a phloroglucinol composition and a preparation method thereof, aiming at solving the problem of stability of phloroglucinol injection which is easy to oxidize and degrade in the production and storage processes.
The invention provides a phloroglucinol composition which is an aqueous solution of phloroglucinol and 1,3, 5-trimethoxybenzene, wherein the content of the phloroglucinol is 9-11 mg/ml, the content of the 1,3, 5-trimethoxybenzene is 9-11 mu g/ml, and the composition also contains trihydroxybenzoic acid isomer (OH)3C6H2COOH acts as a stabilizer.
The phloroglucinol composition is preferably characterized in that the stabilizer is at least one selected from 2,3, 4-trihydroxybenzoic acid, 2,3, 5-trihydroxybenzoic acid, 2,3, 6-trihydroxybenzoic acid, 2,4, 6-trihydroxybenzoic acid, 3,4, 5-trihydroxybenzoic acid and 2,4, 5-trihydroxybenzoic acid, and the content of the stabilizer is 0.001-0.5 mg/ml; the stabilizer is further preferably at least one selected from 2,3, 4-trihydroxybenzoic acid, 2,3, 5-trihydroxybenzoic acid, 2,3, 6-trihydroxybenzoic acid, 2,4, 6-trihydroxybenzoic acid, 3,4, 5-trihydroxybenzoic acid and 2,4, 5-trihydroxybenzoic acid, and the content of the stabilizer is 0.001-0.25 mg/ml; the stabilizer is preferably one or more of 2,4, 6-trihydroxybenzoic acid and 3,4, 5-trihydroxybenzoic acid, and the content of the stabilizer is 0.001-0.25 mg/ml.
In the phloroglucinol composition, when the stabilizer is 3,4, 5-trihydroxybenzoic acid, the content is 0.001-0.25 mg/ml, preferably 0.001-0.1 mg/ml, and more preferably 0.02-0.1 mg/ml.
In the phloroglucinol composition, when the stabilizer is 2,4, 6-trihydroxybenzoic acid, the content is 0.001-0.25 mg/ml, preferably 0.001-0.018 mg/ml, or 0.018-0.025 mg/ml, or 0.025-0.25 mg/ml.
In the phloroglucinol composition, when the stabilizer is 2,4, 6-trihydroxybenzoic acid and 3,4, 5-trihydroxybenzoic acid, the content of the 2,4, 6-trihydroxybenzoic acid is preferably 0.001-0.1 mg/ml, and the content of the 3,4, 5-trihydroxybenzoic acid is preferably 0.005-0.25 mg/ml; further preferably, the content of 2,4, 6-trihydroxybenzoic acid is 0.01-0.05 mg/ml, and the content of 3,4, 5-trihydroxybenzoic acid is 0.025-0.1 mg/ml; further preferably, the content of 2,4, 6-trihydroxybenzoic acid is 0.01 to 0.025mg/ml, and the content of 3,4, 5-trihydroxybenzoic acid is 0.05 to 0.1 mg/ml.
The phloroglucinol composition preferably further comprises a pH regulator, and the pH of a composition solution is 3.0-5.0.
Wherein the pH regulator is preferably one or more selected from hydrochloric acid, boric acid, carbonic acid, tartaric acid, and sodium tartrate.
The phloroglucinol composition preferably also contains an osmotic pressure regulator sodium chloride, and the content of the sodium chloride is 6.5-7.5 mg/ml.
The invention also provides a preparation method of the phloroglucinol composition, which comprises the following steps:
(1) adding phloroglucinol, 1,3, 5-trimethoxybenzene, a stabilizer and sodium chloride in a prescription amount into pure water, heating and stirring for dissolving;
(2) adjusting the pH of the solution obtained in the step (1) to 3.0-5.0 by using a pH regulator to obtain the phloroglucinol composition;
the preparation process is protected by filling conventional inert gas.
The preparation method of the phloroglucinol composition has the advantage that the heating and stirring temperature in the step (1) is preferably 30-60 ℃.
In the preparation method of the phloroglucinol composition, the pH of the composition solution is preferably adjusted to 3.5-4.5 in the step (2).
The conventional inert gas is preferably nitrogen, carbon dioxide or a noble gas.
14. Trihydroxybenzoic acid (OH)3C6H2The application of COOH as a stabilizer in enhancing the stability of phloroglucinol liquid preparations.
Has the advantages that: the phloroglucinol composition prepared by taking trihydroxybenzoic acid as a stabilizer has good stability, and reduces the risk of drug interaction by removing the stabilizer, a pH regulator and an osmotic pressure regulator without adding other components, wherein the stabilizer reduces the oxidative degradation of phloroglucinol and effectively overcomes the defect of poor stability of the prior phloroglucinol product, and the stabilizer is not reported in any safety aspect at present. In addition, the preparation method of the phloroglucinol composition provided by the invention is simple and feasible, the process is controllable, and the industrial operability is strong, so that a good foundation is laid for developing phloroglucinol injection.
Detailed Description
The following are specific embodiments of the present invention, which are intended to be further illustrative, but not limiting, of the invention.
Comparative example 1 No stabilizer
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 30-40 ℃ to dissolve, adding a proper amount of hydrochloric acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen gas in the solution in the preparation process to protect, thereby preparing a comparative medicine solution 1.
Comparative example 2 addition of antioxidant sodium metabisulfite
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 2.8g of sodium chloride and 0.01g of sodium metabisulfite, adding pure water to 400ml, heating and stirring at 30-40 ℃ to dissolve, adding a proper amount of hydrochloric acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen gas in the solution for protection in the preparation process to prepare a comparative medicine solution.
Example 1
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.02g of 2,3, 4-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 30-40 ℃ to dissolve, adding a proper amount of hydrochloric acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen in the solution during the preparation process to protect, thus obtaining the composition solution.
Example 2
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.004g of 2,4, 5-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 30-40 ℃ for dissolving, adding a proper amount of boric acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling argon for protection in the solution during the preparation process to obtain the composition solution.
Example 3
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.008g of 3,4, 5-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 30-40 ℃ for dissolving, adding a proper amount of tartaric acid and sodium tartrate to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen gas into the solution in the preparation process for protection, thus preparing the composition solution.
Example 4
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.04g of 3,4, 5-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 30-40 ℃ to dissolve, adding a proper amount of sodium hydrochloride to adjust the pH value to 3.5-4.5, stirring uniformly, and filling argon in the solution during the preparation process to protect, thus obtaining the composition solution.
Example 5
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.012g of 2,4, 6-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 40-50 ℃ to dissolve, adding a proper amount of hydrochloric acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen in the solution in the preparation process for protection to obtain the composition solution.
Example 6
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.010g of 2,4, 6-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 40-50 ℃ to dissolve, adding a proper amount of carbonic acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen in the solution during the preparation process to protect, thus obtaining the composition solution.
Example 7
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.004g of 2,4, 6-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 40-50 ℃ to dissolve, adding a proper amount of carbonic acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling carbon dioxide into the solution in the preparation process to protect, thus preparing the composition solution.
Example 8
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.007g of 2,4, 6-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 50-60 ℃ to dissolve, adding a proper amount of carbonic acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen in the solution during the preparation process to protect, thus obtaining the composition solution.
Example 9
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.0004g of 2,4, 6-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 40-50 ℃ to dissolve, adding a proper amount of hydrochloric acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling argon in the solution during the preparation process to protect, thus obtaining the composition solution.
Example 10
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.1g of 2,4, 6-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 40-50 ℃ to dissolve, adding a proper amount of tartaric acid and sodium tartrate to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen gas into the solution in the preparation process to protect, thus preparing the composition solution.
Example 11
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.008g of 2,4, 6-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 40-50 ℃ to dissolve, adding a proper amount of hydrochloric acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling argon in the solution during the preparation process to protect, thus obtaining the composition solution.
Example 12
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.010g of 2,4, 6-trihydroxybenzoic acid, 0.020g of 3,4, 5-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 50-60 ℃ for dissolving, adding a proper amount of tartaric acid and sodium tartrate to adjust the pH value to 3.5-4.5, uniformly stirring, and filling nitrogen gas in the solution for protection in the preparation process to obtain a composition solution.
Example 13
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.008g of 2,4, 6-trihydroxybenzoic acid, 0.032g of 3,4, 5-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 40-50 ℃ for dissolving, adding a proper amount of hydrochloric acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling argon gas in the solution for protection in the preparation process to obtain a composition solution.
Example 14
Weighing 4g of phloroglucinol, 0.04g of 1,3, 5-trimethoxybenzene, 0.004g of 2,4, 6-trihydroxybenzoic acid, 0.04g of 3,4, 5-trihydroxybenzoic acid and 2.8g of sodium chloride, adding pure water to 400ml, heating and stirring at 40-50 ℃ for dissolving, adding a proper amount of carbonic acid to adjust the pH value to 3.5-4.5, stirring uniformly, and filling nitrogen gas in the solution for protection in the preparation process to obtain a composition solution.
Example 15
TABLE 1
The properties, pH, content, related substances and the like of the sample are respectively considered, wherein the content of trimethyl phloroglucinol accounts for 10 mu g/ml and 100%, the content of phloroglucinol accounts for 10mg/ml and 100%, the determination method refers to 2015 version Chinese pharmacopoeia and national drug standard phloroglucinol injection YBH00352013, and the determination method of the content of the related substances refers to European pharmacopoeia 9.7. Example 15 is a mass characteristic analysis of the samples of comparative examples 1 to 2 and examples 1 to 14, and the results (table 1) show that the compositions prepared in comparative example 1 and examples have similar properties, pH, phloroglucinol and trimethylphloroglucinol, but have large differences in the contents of the relevant substances, wherein no antioxidant or stabilizer is added in comparative example 1, and the content of the relevant substances is as high as 0.51%, and the antioxidant sodium metabisulfite is added in comparative example 2, but the content of the relevant substances in the samples is 0.35%, while the content of the relevant substances in the compositions in examples 1 to 7 is not more than 0.30%, indicating that the phloroglucinol composition of the present invention has significant advantages in stability.
Example 16 stability study
The stability after placing the samples of comparative examples 1-2 and examples 1-14 under the conditions of 25 ℃. + -. 2 ℃/60% RH. + -. 5% RH for 24 months and 40 ℃. + -. 2 ℃/75% RH. + -. 5% RH for 6 months, respectively, is shown in tables 2 and 3.
TABLE 2 Long term test stability
TABLE 3 stability of accelerated test
Claims (17)
1. A phloroglucinol composition is an aqueous solution containing phloroglucinol and 1,3, 5-trimethoxybenzene, wherein the content of the phloroglucinol is 9-11 mg/ml, the content of the 1,3, 5-trimethoxybenzene is 9-11 mu g/ml,the method is characterized in that: the composition also contains trihydroxybenzoic acid (OH)3C6H2COOH as a stabilizer.
2. The phloroglucinol composition according to claim 1, further characterized by: the composition also contains a pH regulator and an osmotic pressure regulator, wherein the pH regulator regulates the pH of a composition solution to be 3-5, the osmotic pressure regulator is sodium chloride, and the content is preferably 6.5-7.5 mg/ml.
3. Phloroglucinol compositions according to claim 2, characterized in that the pH adjusting agent is selected from one or more of hydrochloric acid, boric acid, carbonic acid, tartaric acid, sodium tartrate.
4. Phloroglucinol compositions according to claim 2, characterized in that: the stabilizer is at least one selected from 2,3, 4-trihydroxybenzoic acid, 2,3, 5-trihydroxybenzoic acid, 2,3, 6-trihydroxybenzoic acid, 2,4, 6-trihydroxybenzoic acid, 3,4, 5-trihydroxybenzoic acid and 2,4, 5-trihydroxybenzoic acid, and the content of the stabilizer is 0.001-0.5 mg/ml.
5. The phloroglucinol composition according to claim 4, wherein the stabilizer is at least one selected from the group consisting of 2,3, 4-trihydroxybenzoic acid, 2,3, 5-trihydroxybenzoic acid, 2,3, 6-trihydroxybenzoic acid, 2,4, 6-trihydroxybenzoic acid, 3,4, 5-trihydroxybenzoic acid, and 2,4, 5-trihydroxybenzoic acid, and is contained in an amount of 0.001 to 0.25 mg/ml.
6. Phloroglucinol compositions according to claim 5, characterized in that: the stabilizer is selected from one or more of 2,4, 6-trihydroxybenzoic acid and 3,4, 5-trihydroxybenzoic acid, and the content is 0.001-0.25 mg/ml.
7. Phloroglucinol compositions according to claim 5, characterized in that: the stabilizer is 3,4, 5-trihydroxybenzoic acid, and the content is 0.001-0.25 mg/ml; the content is preferably 0.001 to 0.1mg/ml, and more preferably 0.02 to 0.1 mg/ml.
8. Phloroglucinol compositions according to claim 5, characterized in that: the stabilizer is 2,4, 6-trihydroxybenzoic acid, and the content is 0.001-0.25 mg/ml.
9. Phloroglucinol compositions according to claim 8, characterized in that: the stabilizer is 2,4, 6-trihydroxybenzoic acid, and the content is 0.001-0.018 mg/ml.
10. Phloroglucinol compositions according to claim 8, characterized in that: the stabilizer is 2,4, 6-trihydroxybenzoic acid, and the content is 0.018-0.025 mg/ml.
11. Phloroglucinol compositions according to claim 8, characterized in that: the stabilizer is 2,4, 6-trihydroxybenzoic acid, and the content is 0.025-0.25 mg/ml.
12. Phloroglucinol compositions according to claim 5, characterized in that: the stabilizer is 2,4, 6-trihydroxybenzoic acid and 3,4, 5-trihydroxybenzoic acid, the content of the 2,4, 6-trihydroxybenzoic acid is 0.001-0.1 mg/ml, and the content of the 3,4, 5-trihydroxybenzoic acid is 0.005-0.25 mg/ml; preferably, the content of 2,4, 6-trihydroxybenzoic acid is 0.01-0.05 mg/ml, and the content of 3,4, 5-trihydroxybenzoic acid is 0.025-0.1 mg/ml; further preferably, the content of 2,4, 6-trihydroxybenzoic acid is 0.01 to 0.025mg/ml, and the content of 3,4, 5-trihydroxybenzoic acid is 0.05 to 0.1 mg/ml.
13. A process for the preparation of a phloroglucinol composition according to any of claims 2-12, characterized by comprising the steps of:
a. adding phloroglucinol, 1,3, 5-trimethoxybenzene, trihydroxybenzoic acid serving as a stabilizer and an osmotic pressure regulator into pure water according to the prescription amount, and heating, stirring and dissolving;
b. adjusting the pH of the solution obtained in the step a to 3.0-5.0 by using a pH regulator to obtain the phloroglucinol composition as claimed in any one of claims 2 to 9.
Wherein, the preparation process is filled with conventional inert gas for protection.
14. The method of manufacturing according to claim 13, wherein: in the step a, the heating and stirring temperature is 30-60 ℃.
15. The method of manufacturing according to claim 13, wherein: and (c) adjusting the pH value of the composition solution to 3.5-4.5 in the step (b).
16. The method of manufacturing according to claim 13, wherein: the conventional inert gas is nitrogen, carbon dioxide or a rare gas.
17. Trihydroxybenzoic acid (OH)3C6H2The application of COOH as a stabilizer in enhancing the stability of phloroglucinol liquid preparations.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910832085.2A CN112438948A (en) | 2019-09-04 | 2019-09-04 | Phloroglucinol composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910832085.2A CN112438948A (en) | 2019-09-04 | 2019-09-04 | Phloroglucinol composition and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112438948A true CN112438948A (en) | 2021-03-05 |
Family
ID=74734900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910832085.2A Withdrawn CN112438948A (en) | 2019-09-04 | 2019-09-04 | Phloroglucinol composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112438948A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115282132A (en) * | 2022-02-10 | 2022-11-04 | 郑州大学第一附属医院 | Compound for relieving ERCP (enterospasm pulmonary cholangitis) and preparation method thereof |
| CN115721631A (en) * | 2022-12-08 | 2023-03-03 | 绪必迪药业(沧州)有限公司 | Preparation method of phloroglucinol injection |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101856324A (en) * | 2010-06-10 | 2010-10-13 | 南京生命能科技开发有限公司 | Method for preparing phloroglucinol injection |
| EP2489347A1 (en) * | 2010-02-26 | 2012-08-22 | Société Delpharm s.a.s. | Process for the production of injectable preparations of phloroglucinol and the injectable preparations so obtained |
-
2019
- 2019-09-04 CN CN201910832085.2A patent/CN112438948A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2489347A1 (en) * | 2010-02-26 | 2012-08-22 | Société Delpharm s.a.s. | Process for the production of injectable preparations of phloroglucinol and the injectable preparations so obtained |
| CN101856324A (en) * | 2010-06-10 | 2010-10-13 | 南京生命能科技开发有限公司 | Method for preparing phloroglucinol injection |
Non-Patent Citations (3)
| Title |
|---|
| BAUR，EMIL等: "Kinetics of phloroglucinolcarboxylic acid", 《HELVETICA CHIMICA ACTA》 * |
| BAUR,EMIL等: "Kinetik der Phloroglueincarbonsaure", HELVETICA CHIMICA ACTA * |
| 彭文达等: "间苯三酚注射液的研制", 中国药物与临床 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115282132A (en) * | 2022-02-10 | 2022-11-04 | 郑州大学第一附属医院 | Compound for relieving ERCP (enterospasm pulmonary cholangitis) and preparation method thereof |
| CN115282132B (en) * | 2022-02-10 | 2024-01-30 | 郑州大学第一附属医院 | Complex for relieving ERCP biliary spasm and its preparation method |
| CN115721631A (en) * | 2022-12-08 | 2023-03-03 | 绪必迪药业(沧州)有限公司 | Preparation method of phloroglucinol injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6635927B2 (en) | Method for Producing a Stable Low Concentration Injectable Solution of Noradrenaline | |
| RU2362560C2 (en) | Pharmaceutical preparative form | |
| KR100533407B1 (en) | Nmda receptor agonist pharmaceutical compositions | |
| CN112438948A (en) | Phloroglucinol composition and preparation method thereof | |
| CN103239684A (en) | Zedoary oil injection and preparation method thereof | |
| CN105078909B (en) | Cisatracurium besilate freeze-dried composition for injection and preparation method thereof | |
| EP3331509B1 (en) | Stable liquid injectable solution of midazolam and pentazocine | |
| WO2021012686A1 (en) | Naloxone hydrochloride injection and preparation method therefor | |
| CN113350276A (en) | Preparation method and packaging method of octreotide acetate injection | |
| CN110090225B (en) | Edaravone sodium chloride injection and preparation method thereof | |
| JP4959335B2 (en) | Methylphenidate solution and related administration and manufacturing methods | |
| CN108324683A (en) | A kind of big infusion Edaravone Injection and its preparation process of stabilization | |
| CN109481459B (en) | Compound electrolyte glucose injection and preparation method thereof | |
| WO2016084099A1 (en) | Soft gelatin capsule composition of anti-tussive agents | |
| CN110693861A (en) | Terbutaline sulfate solution preparation for aerosol inhalation and preparation method thereof | |
| CN111544421B (en) | Ambroxol hydrochloride solution for inhalation and preparation method thereof | |
| CN113546039A (en) | Dalafinil transdermal preparation composition and preparation method of dalafinil transdermal preparation | |
| CN103202805B (en) | Vinpocetine-containing pharmaceutical composition for injection and preparation method thereof | |
| CN102302495A (en) | Tropisetron hydrochloride medicament composition for injection | |
| CN102166185A (en) | Isotonic naloxone injection and preparation method thereof | |
| CN115737571B (en) | Pentazocine Xin Zhiji and preparation method and application thereof | |
| CN110101875B (en) | Gadoxetic acid disodium injection pharmaceutical composition and preparation method thereof | |
| CN106937944A (en) | A kind of injection metronidazole freeze-dried powder and preparation method thereof | |
| CN115429800A (en) | Stable low-concentration atropine eye preparation and preparation method and application thereof | |
| WO2022247609A1 (en) | Tizanidine liquid preparation and use thereof |
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 | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20210305 |