CN111012737A - Flurbiprofen sodium gel and preparation method thereof - Google Patents
Flurbiprofen sodium gel and preparation method thereof Download PDFInfo
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- CN111012737A CN111012737A CN202010098382.1A CN202010098382A CN111012737A CN 111012737 A CN111012737 A CN 111012737A CN 202010098382 A CN202010098382 A CN 202010098382A CN 111012737 A CN111012737 A CN 111012737A
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- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
The invention belongs to the technical field of medicines, and relates to a flurbiprofen sodium gel preparation formula and an application thereof, wherein the flurbiprofen sodium gel preparation comprises the following components in parts by weight: according to the total weight of the pharmaceutical preparation, the flurbiprofen sodium is 0.5-5%, the matrix is 0.5-5%, the solvent is 50-95%, the preservative is 0.1-1.0%, the pH regulator is 0-5%, and the percutaneous absorption penetration enhancer is 0.1-20%. Compared with oral flurbiprofen, the flurbiprofen sodium skin external gel can effectively avoid adverse reactions of gastrointestinal tracts, and can be used for diminishing inflammation, relieving fever and easing pain. The flurbiprofen sodium gel disclosed by the invention is simple in formula components and process, small in organic solvent consumption, environment-friendly, suitable for industrial mass production, stable in product quality and capable of meeting the medicinal requirements.
Description
The present application proposes a priority request for the following chinese patent applications:
application No.: 201910134586.3
Application date: 23.02 month 2019
Application name: transdermal drug delivery preparation of flurbiprofen salt and preparation method thereof
Technical Field
The invention belongs to the field of medicinal preparations, and particularly relates to flurbiprofen sodium gel and a preparation method thereof.
Background
Flurbiprofen (FLB) is an aryl propionic acid non-steroidal anti-inflammatory drug, is a non-selective cyclooxygenase inhibitor, and has strong anti-inflammatory, analgesic and antipyretic functions. The medicinal compounds of flurbiprofen are mainly flurbiprofen, flurbiprofen sodium and flurbiprofen axetil. According to the administration route, the characteristics of the preparation and the like, different medicinal compounds are respectively selected to develop into preparation products for sale. The flurbiprofen is available in the market at home and abroad in the following dosage forms: tablet, granule, capsule, gel patch and patch. The flurbiprofen sodium is available in the form of eye drops and eye gel. Flurbiprofen axetil is only available as an injection on the market.
The side effect of orally taken flurbiprofen is mainly gastrointestinal adverse reaction, and digestive tract ulcer and hemorrhage are easily caused. The adverse reaction of the gastrointestinal tract can be effectively avoided by transdermal administration, the adverse reaction rate of the gel plaster is about 7.38 percent, and the adverse reaction rate is mainly pruritus, rubella, rash, macula and pain, and the analysis reason is mainly caused by poor air permeability of the ointment matrix and the gel plaster.
The gel is a thick semisolid preparation, has the advantages of high absorption speed, good biocompatibility, uniform texture, easy spreading and washing, convenient use, good patient compliance and the like, and the main components of the hydrogel preparation are water, a small amount of gel matrix, humectant, bacteriostatic agent and the like, so that the possibility of adverse reaction caused by the matrix is obviously reduced. Therefore, the flurbiprofen gel is researched and developed, and can quickly exert the drug effect, enhance the compliance of the flurbiprofen gel and reduce the adverse reaction rate.
The concentration of flurbiprofen sodium ophthalmic gel on the market at present is 0.03%, and the topical analgesic effect of transdermal administration cannot be met.
Therefore, it is necessary to develop a suitable concentration of flurbiprofen gel formulation for anti-inflammation, analgesia and antipyresis.
Disclosure of Invention
The invention aims to provide a flurbiprofen sodium gel preparation formula with good transdermal absorption effect, the preparation components and the process of the formula are simple, compared with the method for preparing hydrogel by directly using flurbiprofen, the flurbiprofen sodium gel preparation formula has the advantages of enhanced transdermal performance, small organic solvent consumption, environmental friendliness, suitability for industrial mass production, stable product quality and accordance with medicinal requirements.
The water solubility of flurbiprofen is poor, the saturation solubility of the flurbiprofen in pure water at room temperature is about 0.033 mg/ml, the water solubility of the flurbiprofen sodium is obviously improved, the saturation solubility is about 36 mg/ml, and the flurbiprofen is more than 1000 times higher than that of the flurbiprofen. The test results show that when the flurbiprofen is used as a raw material to prepare the gel, a large amount of organic solvent is consumed, about 40% of isopropanol is used as a solvent for preparing 1% of specification, the water solubility of the flurbiprofen sodium is obviously improved, and about 3% (calculated by the flurbiprofen) specification hydrogel can be prepared without using an organic solvent.
In order to compare the transdermal capacities of flurbiprofen and flurbiprofen sodium, 40% isopropanol is used as a solvent, flurbiprofen gel and flurbiprofen sodium gel with the specification of 1% (calculated by flurbiprofen) are respectively prepared by the same prescription process, and Franz diffusion tests on rat abdominal skin prove that the flurbiprofen sodium is faster in transdermal release and stronger in transdermal capacity.
Through experimental grope, the invention provides a flurbiprofen sodium gel preparation with high transdermal absorption efficiency and less organic solvent, and the pharmaceutical preparation comprises: according to the total weight of the pharmaceutical preparation, the active ingredient flurbiprofen sodium is 0.5-5%, the matrix is 0.5-5%, the solvent is 50-95%, and the preservative is 0.1-1.0%.
Further, the pharmaceutical formulation comprises: according to the total weight of the pharmaceutical preparation, the active ingredient flurbiprofen sodium is 0.1-3%, the matrix is 0.5-5%, the solvent is 70-95%, and the preservative is 0.1-1.0%.
Further, the pharmaceutical formulation further comprises: the pH regulator is 0-5% of the total weight of the pharmaceutical preparation.
Further, the pharmaceutical formulation further comprises: the percutaneous absorption penetration enhancer is 0.1-20% of the total weight of the pharmaceutical preparation.
Further, the matrix is one or more of carbomer, hydroxypropyl methylcellulose and sodium carboxymethylcellulose, preferably carbomer.
Further, the solvent is one or more of isopropyl alcohol, glycerol, propylene glycol, ethanol and purified water, preferably one or more of purified water, propylene glycol, isopropyl alcohol and ethanol.
Further, the antiseptic is one or more of methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, benzoic acid, sodium benzoate, chlorhexidine acetate, thimerosal, and phenoxyethanol, preferably one or more of methyl hydroxybenzoate, ethyl hydroxybenzoate, and propyl hydroxybenzoate.
Further, the pH regulator is one or more of triethanolamine, diethanolamine, tromethamine, sodium hydroxide and triethylamine, preferably one or more of triethanolamine and tromethamine.
Further, the percutaneous absorption penetration enhancer is one or more of menthol, peppermint oil, laurocapram, N-methylpyrrolidone, isopropyl myristate and crotamiton, preferably one or more of menthol, isopropyl myristate and crotamiton.
The invention also provides a preparation method of the flurbiprofen sodium gel, which comprises the following steps of but is not limited to:
1) adding the matrix into water, and swelling to obtain gel matrix.
2) Adding antiseptic, percutaneous absorption promoter, and active ingredient into solvent, dissolving, adding into gel matrix, and stirring.
According to a specific embodiment of the invention, 130g of carbomer is added into 4900g of water, 250g of triethanolamine and 1500g of propylene glycol are added after the carbomer is fully swelled, and the gel matrix is obtained after stirring for 30 minutes. Taking 1000g of isopropanol, adding 10g of ethylparaben and 10g of menthol, stirring for 10 minutes, adding 2000g of water, adding 200g of flurbiprofen sodium, dissolving, adding into a gel matrix, and stirring for 30 minutes to obtain the oral liquid.
The invention also comprises the application of the flurbiprofen sodium gel prepared by the method in diminishing inflammation, relieving heat and easing pain.
The flurbiprofen sodium gel prepared by the method has the following advantages:
1. the flurbiprofen sodium gel prepared by the method is administrated through skin, gastrointestinal adverse reactions caused by oral flurbiprofen preparation can be avoided, and the patient compliance is good;
2. the formula of the invention has simple components and process, obviously reduces the use amount of organic solvent, is environment-friendly and is suitable for industrial mass production;
3. the flurbiprofen sodium gel prepared by the method has good transdermal absorption effect and stable product quality, and meets the medicinal requirements.
Drawings
FIG. 1 is a substance-related detection pattern of a sample with stability for 6 months of accelerated test;
FIG. 2 is a substance detection pattern of a long-term test 6-month stability sample.
Detailed Description
The present application will be described in further detail with reference to specific examples. The following examples are intended to be illustrative of the present application only and should not be construed as limiting the present application.
The reagents and raw materials used in the invention are commercially available.
Example 1 comparative experiment of transdermal absorption Effect
The formula and the preparation method of the 1 percent flurbiprofen gel comprise the following steps:
adding 20g of hydroxypropyl methylcellulose K100M into 570g of water, and fully swelling to obtain a gel matrix for later use; adding 10g of flurbiprofen into 400g of isopropanol, dissolving, adding into the gel matrix, and stirring uniformly to obtain the flurbiprofen gel, wherein the specification is as follows: 1% (calculated as flurbiprofen).
The formula of the 1% flurbiprofen sodium gel and the preparation method are as follows:
adding 20g of hydroxypropyl methylcellulose K100M into 567.6g of water, and fully swelling to obtain a gel matrix for later use; adding 12.4g of flurbiprofen sodium into 400g of isopropanol, dissolving, adding into a gel matrix, and stirring uniformly to obtain the flurbiprofen sodium gel, wherein the specification is as follows: 1% (calculated as flurbiprofen).
Test method for comparative transdermal capacity: the abdominal skin of an isolated rat is fixed on a vertical Franz diffusion cell, and the skin receiving area is 3.14cm2Taking about 0.3g of gel, uniformly smearing the gel on skin, taking a phosphate buffer solution with the pH value of 7.4 at 32 ℃ as a receiving solution, completely taking out the receiving solution for 0.5, 1, 2, 4 and 6 hours respectively to measure the content, supplementing the receiving solution at 32 ℃, and calculating the cumulative permeation amount at each time point;
table 1: cumulative penetration of 1% (calculated as flurbiprofen) of flurbiprofen gel and flurbiprofen sodium gel through rat abdominal skin (mcg/cm)2）
The experimental results in table 1 show that the transdermal performance of flurbiprofen sodium is better, the cumulative permeation amount of flurbiprofen sodium gel after passing through rat skin for 0.5h and 1.6 h is about 1.5 and 1.6 times of that of flurbiprofen respectively, and the cumulative release degree of both 4h and 6h is more than 80%.
Example 2
The formula and the preparation method are as follows:
150g of carbomer was added to 6210g of water and allowed to swell sufficiently. Adding 60g of sodium hydroxide into 1000g of water, dissolving, adding into the carbomer solution, and stirring for 30 minutes to obtain the gel matrix. Taking 1000g of ethanol and 500g of propylene glycol, adding 10g of benzoic acid, 10g of isopropyl myristate and 10g of peppermint oil, stirring for 10 minutes, adding 1000g of water, adding 50g of flurbiprofen sodium, dissolving, adding into a gel matrix, and stirring for 30 minutes to obtain the oral liquid.
Example 3
The formula and the preparation method are as follows:
adding 300g of sodium carboxymethylcellulose into 6560g of water, fully swelling, adding 1000g of glycerol, and uniformly stirring for later use. Adding 5g of methyl hydroxybenzoate, 15g of ethylparaben, 10g of laurocapram and 10g of menthol into 2000g of ethanol, stirring for 10 minutes, adding 100g of flurbiprofen sodium, dissolving, adding into the gel matrix, and stirring for 30 minutes.
Example 4
The formula and the preparation method are as follows:
adding 130g of carbomer into 5000g of water, fully swelling, adding 250g of triethanolamine and 1500g of propylene glycol, and stirring for 30 minutes to obtain the gel matrix. Taking 1000g of isopropanol, adding 10g of ethylparaben and 10g of menthol, stirring for 10 minutes, adding 2000g of water, adding 100g of flurbiprofen sodium, dissolving, adding into a gel matrix, and stirring for 30 minutes to obtain the oral liquid.
Example 5
The formula and the preparation method are as follows:
adding 130g of carbomer into 4900g of water, fully swelling, adding 250g of triethanolamine and 1500g of propylene glycol, and stirring for 30 minutes to obtain the gel matrix. Taking 1000g of isopropanol, adding 10g of ethylparaben and 10g of menthol, stirring for 10 minutes, adding 2000g of water, adding 200g of flurbiprofen sodium, dissolving, adding into a gel matrix, and stirring for 30 minutes to obtain the oral liquid.
Example 6
The formula and the preparation method are as follows:
adding 130g of carbomer into 4800g of water, fully swelling, adding 250g of triethanolamine and 1500g of propylene glycol, and stirring for 30 minutes to obtain the gel matrix. Taking 1000g of isopropanol, adding 10g of ethylparaben and 10g of menthol, stirring for 10 minutes, adding 2000g of water, adding 300g of flurbiprofen sodium, dissolving, adding into a gel matrix, and stirring for 30 minutes to obtain the oral liquid.
Example 7
The formula and the preparation method are as follows:
120g of carbomer was added to 4270g of water and allowed to swell sufficiently. Adding 300g tromethamine into 1000g water, dissolving, adding into carbomer solution, and stirring for 30 min to obtain gel matrix. Adding 2000g of isopropanol into 10g of ethylparaben, stirring for 10 minutes, adding 2000g of water, adding 300g of flurbiprofen sodium, dissolving, adding into the gel matrix, and stirring for 30 minutes to obtain the gel.
Example 8
The formula and the preparation method are as follows:
adding 150g of carbomer into 5820g of water, fully swelling, adding 300g of triethanolamine, and stirring for 30 minutes to obtain the gel matrix. Taking 1000g of isopropanol, adding 5g of ethylparaben, 5g of propyl hydroxybenzoate, 10g of menthol and 10g of laurocapram, stirring for dissolving, adding into the gel matrix, and stirring for 10 minutes; and adding 1700g of water into 500g of polysorbate 80, stirring uniformly, adding 500g of flurbiprofen sodium, dissolving, adding into the gel matrix, and stirring for 30 minutes to obtain the gel.
Example 9 measurement of transdermal absorption Effect of flurbiprofen sodium gel
The transdermal absorption effect through rat skin was measured in example 4, example 5 and example 6, respectively.
The abdominal skin of an isolated rat is fixed on a vertical Franz diffusion cell, and the skin receiving area is 3.14cm2Taking about 0.3g of gel, uniformly smearing the gel on skin, taking 32 ℃ phosphate buffer solution with pH7.4 as receiving solution, completely taking out the receiving solution in 0.5, 1, 2, 4 and 6 hours respectively to measure the content, supplementing the receiving solution with 32 ℃, and calculating the average cumulative permeation amount at each time point, wherein n = 6.
Table 2: cumulative penetration of flurbiprofen sodium gel through rat abdominal skin (mcg/cm)2）
The transdermal results show that the preparations of example 4, example 5 and example 6 have better transdermal performance, and the cumulative permeation amount at each time point increases along with the increase of the specification of the preparation.
Example 10 flurbiprofen sodium gel pharmacodynamic study, skin irritation and topical hypersensitivity testing
1. Study of pharmacodynamics
Pharmacodynamic tests were performed on example 4, example 5 and example 6: 60 healthy male Wistar rats are randomly divided into a normal control group, a model control group, a blank control group, a flurbiprofen sodium gel-1 group, a flurbiprofen sodium gel-2 group and a flurbiprofen sodium gel-3 group, wherein each group comprises 10 rats, the normal control group is injected with physiological saline through hind limb knee joints, and the other groups are injected with 4% of papain solution through the hind limb knee joints. After knee joint injection, the normal control group and the model control group are smeared with about 0.1g of physiological saline, the blank control group is smeared with about 0.1g of blank gel, the flurbiprofen sodium gel-1 group, the flurbiprofen sodium gel-2 group and the flurbiprofen sodium gel-3 group are smeared with about 0.1g of flurbiprofen sodium gel of example 4, example 5 or example 6 respectively, and the administration times are as follows: the administration was carried out once a day for 7 days, and the swollen degree of joint and the hindlimb supporting force of the rats were recorded daily, and the COX-1 and COX-2 contents in the washing solution of the toe joint tissue of each rat were measured on day 7. The results show that the severe red swelling phenomenon of the joints occurs in the model control group and the blank control group along with the extension of the molding time, the hind limb supporting force is obviously weakened, and the two groups of detection indexes have no obvious difference; the joints of the normal control group have no abnormal change; compared with a blank control group and a model control group, the degree of redness and swelling of the flurbiprofen sodium gel-1 group, the flurbiprofen sodium gel-2 group and the flurbiprofen sodium gel-3 group is obviously weaker; the swelling degrees of the flurbiprofen sodium gel-2 group and the flurbiprofen sodium gel-3 are not obviously different and are mild red swelling; the hindlimb supporting force of 3 groups of rats given flurbiprofen sodium gel is obviously greater than that of the model control group and the blank control group, and the COX-1 and COX-2 contents are obviously lower than those of the model control group and the blank control group. The flurbiprofen sodium gel is proved to be capable of obviously inhibiting COX-1 and COX-2 after percutaneous absorption, reducing swelling and pain of arthritis, exerting curative effect and having a certain dose-effect relationship.
2. Skin irritation and topical hypersensitivity testing
A local allergy test was performed on example 5: using 18 albino guinea pigs (male and female halves), randomly dividing a blank control group, a flurbiprofen sodium gel group and a positive control group (2, 4-dinitrochlorobenzene), wherein 6 guinea pigs (male and female halves) are subjected to topical sensitization on the right back on days 1, 8 and 15 of the test; on test day 15, the left flank was challenged with drug and skin allergic reactions were observed at 6h, 24h and 48h post challenge. As a result: the average value of the excitation reactions of the flurbiprofen sodium gel group and the blank control group is 0, namely, no anaphylactic reaction exists, while the average value of the excitation reactions of the positive control group is 1.3, the sensitization rate is 100%, and the strong sensitization is realized.
The skin irritation test was performed for example 5: the method is characterized in that 6 New Zealand white rabbits (male and female halves) are used, the same body left and right sides self-contrast method is adopted, the product is given to the left side, the control product (blank gel) is given to the right side for smearing administration, and no erythema or edema is seen in an administration unit during administration and within 3 days after no administration, so that the method is proved that: under the test condition, the product has no stimulation effect on rabbit skin.
Example 11 flurbiprofen sodium gel stability study
Pilot scale sample preparation was performed according to the recipe procedure of example 5, batch: 100kg, filling the gel into a medicinal aluminum hose, sealing the tail, and performing an accelerated and long-term stability test under the accelerated test conditions: 40 ℃ plus or minus 2 ℃, RH75 percent plus or minus 5 percent, and long-term test conditions: the method comprises the steps of sampling and inspecting the characters, pH value, viscosity, related substances and content at 25 +/-2 ℃ and RH60 +/-5%, and respectively carrying out accelerated test on a related substance detection map of a 6-month stability sample such as a figure 1 and a related substance detection map of a long-term test 6-month stability sample such as a figure 2. The results are shown in the following table:
accelerated test results (conditions 40 ℃ C. + -. 2 ℃ C., RH75% + -. 5%)
Long-term test results (conditions 25 ℃ C. + -. 2 ℃ C., RH60% + -. 5%)
The foregoing is a more detailed description of the present application in connection with specific embodiments thereof, and it is not intended that the present application be limited to the specific embodiments thereof. For those skilled in the art to which the present application pertains, several simple deductions or substitutions may be made without departing from the concept of the present application, and all should be considered as belonging to the protection scope of the present application.
Claims (10)
1. A flurbiprofen sodium gel pharmaceutical formulation, comprising: according to the total weight of the pharmaceutical preparation, the active ingredient flurbiprofen sodium is 0.5-5%, the matrix is 0.5-5%, the solvent is 50-95%, and the preservative is 0.1-1.0%.
2. The pharmaceutical formulation of claim 1, wherein the pharmaceutical formulation comprises: according to the total weight of the pharmaceutical preparation, the active ingredient flurbiprofen sodium is 0.5-3%, the matrix is 0.5-5%, the solvent is 70-95%, and the preservative is 0.1-1.0%.
3. The pharmaceutical formulation of claim 2, further comprising a pH adjusting agent, wherein the pH adjusting agent is 0-5% by weight of the pharmaceutical formulation.
4. The pharmaceutical preparation of claim 2, further comprising a transdermal penetration enhancer in an amount of 0.1 to 20% by weight based on the total weight of the pharmaceutical preparation.
5. The pharmaceutical formulation of claim 2, wherein the matrix is one or more of carbomer, hypromellose, and sodium carboxymethylcellulose.
6. The pharmaceutical formulation of claim 2, wherein the solvent is one or more of isopropanol, glycerol, propylene glycol, ethanol, purified water.
7. The pharmaceutical preparation according to claim 2, wherein the preservative is one or more of methylparaben, ethylparaben, propylparaben, benzoic acid, sodium benzoate, chlorhexidine acetate, thimerosal, and phenoxyethanol.
8. The pharmaceutical formulation of claim 3, wherein the pH adjusting agent is one or more of triethanolamine, diethanolamine, tromethamine, sodium hydroxide, triethylamine.
9. A pharmaceutical formulation as claimed in claim 4, wherein the transdermal penetration enhancer is one or more of menthol, peppermint oil, laurocapram, N-methylpyrrolidone, isopropyl myristate, crotamiton.
10. Use of a pharmaceutical preparation according to any one of claims 1 to 9 for anti-inflammatory, antipyretic and analgesic purposes.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| CN201910134586 | 2019-02-23 | ||
| CN2019101345863 | 2019-02-23 |
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| CN111012737A true CN111012737A (en) | 2020-04-17 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111904925A (en) * | 2020-04-28 | 2020-11-10 | 湖南九典制药股份有限公司 | Flurbiprofen sodium gel preparation and preparation method and application thereof |
| CN113651689A (en) * | 2021-08-27 | 2021-11-16 | 上海博悦生物科技有限公司 | Novel crystal form of S-flurbiprofen sodium and preparation method thereof |
| CN115969776A (en) * | 2023-02-06 | 2023-04-18 | 湖南九典制药股份有限公司 | Flurbiprofen sodium gel composition and preparation method thereof |
| CN116059383A (en) * | 2023-02-02 | 2023-05-05 | 湖南九典制药股份有限公司 | Flurbiprofen salt gel and crystallization inhibitor thereof |
-
2020
- 2020-02-19 CN CN202010098382.1A patent/CN111012737A/en not_active Withdrawn
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111904925A (en) * | 2020-04-28 | 2020-11-10 | 湖南九典制药股份有限公司 | Flurbiprofen sodium gel preparation and preparation method and application thereof |
| CN113651689A (en) * | 2021-08-27 | 2021-11-16 | 上海博悦生物科技有限公司 | Novel crystal form of S-flurbiprofen sodium and preparation method thereof |
| CN116059383A (en) * | 2023-02-02 | 2023-05-05 | 湖南九典制药股份有限公司 | Flurbiprofen salt gel and crystallization inhibitor thereof |
| CN116059383B (en) * | 2023-02-02 | 2023-09-05 | 湖南九典制药股份有限公司 | Flurbiprofen salt gel and crystallization inhibitor thereof |
| CN115969776A (en) * | 2023-02-06 | 2023-04-18 | 湖南九典制药股份有限公司 | Flurbiprofen sodium gel composition and preparation method thereof |
| CN115969776B (en) * | 2023-02-06 | 2023-08-29 | 湖南九典制药股份有限公司 | Flurbiprofen sodium gel composition and preparation method thereof |
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Application publication date: 20200417 |