CN111904925A - Flurbiprofen sodium gel preparation and preparation method and application thereof - Google Patents
Flurbiprofen sodium gel preparation and preparation method and application thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of medicines, and relates to a flurbiprofen sodium gel preparation and a preparation method and application thereof, wherein the flurbiprofen sodium gel preparation comprises the following components in percentage by weight: 0.5-5% of flurbiprofen sodium, 0.5-5% of matrix, 50-95% of solvent, 0-5% of pH regulator, 0.1-20% of percutaneous absorption penetration enhancer and 0.1-1.0% of preservative. 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
Technical Field
The invention belongs to the field of medicinal preparations, and particularly relates to a flurbiprofen sodium gel preparation as well as a preparation method and application 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.
CN104546803A, CN1443532A and CN110787150A all use flurbiprofen as a main drug to prepare gel emplastrum and patch, while there is no patent disclosing flurbiprofen sodium as a main drug to prepare transdermal drug delivery preparation, and there is no patent disclosing flurbiprofen or flurbiprofen sodium to prepare transdermal drug delivery gel, but the flurbiprofen sodium ophthalmic gel on the market has a concentration of 0.03%, which cannot satisfy the local analgesic effect of transdermal drug delivery.
Therefore, it is necessary to develop a suitable concentration of flurbiprofen gel formulation having a good transdermal effect 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 and a preparation method thereof, the formula has simple preparation components and process, and compared with the method for preparing hydrogel by directly using flurbiprofen, the flurbiprofen sodium gel preparation formula has the advantages of improved drug-loading rate, enhanced transdermal performance, small organic solvent consumption, environmental friendliness, suitability for industrial mass production, stable product quality and accordance with medicinal requirements.
According to one aspect of the present invention, there is provided a flurbiprofen sodium gel formulation comprising, in weight percent:
0.5-5% of flurbiprofen sodium, 0.5-5% of matrix, 50-95% of solvent, 0-5% of pH regulator, 0.1-20% of percutaneous absorption penetration enhancer and 0.1-1.0% of preservative.
Further, the flurbiprofen sodium gel preparation comprises the following components in percentage by weight: 1.2-5% of flurbiprofen sodium, 0.8-4% of matrix, 70-95% of solvent, 0-4% of pH regulator, 0.1-10% of percutaneous absorption promoter and 0.1-0.5% of preservative.
Further, the pH regulator is one or more of triethanolamine, diethanolamine, tromethamine, sodium hydroxide and triethylamine, preferably one or two of triethanolamine and tromethamine.
Further, the flurbiprofen sodium gel preparation is alkaline, the pH value is not more than 9, and the pH value is preferably 7.01-8.0.
Further, the solvent is one or more of isopropanol, glycerol, propylene glycol, ethanol and purified water.
Further, the solvent comprises water and a non-aqueous solvent, and the mass ratio of the water to the non-aqueous solvent is as follows: 1: 1-10: 1, wherein the water is purified water, and the non-aqueous solvent is one or more of isopropanol, glycerol, propylene glycol and ethanol.
Further, the percutaneous absorption penetration enhancer is one or more of menthol, peppermint oil, laurocapram, N-methylpyrrolidone, isopropyl myristate and crotamiton.
Further, the matrix is one or more of carbomer, hydroxypropyl methylcellulose and sodium carboxymethylcellulose.
Further, the preservative is one or more of methyl hydroxybenzoate, ethyl hydroxybenzoate, propyl hydroxybenzoate, benzoic acid, sodium benzoate, chlorhexidine acetate, thimerosal, and phenoxyethanol.
Further, the flurbiprofen sodium gel may further include one or more of a surfactant, a pigment or an essence, the surfactant is one or more of polysorbate 80, polyoxyethylene hydrogenated castor oil-40, polysorbate 20, polysorbate 40, polysorbate 60, span 20, span 40, span 60 and span 80, the pigment is one or more of indigo, sunset yellow, carmine and lemon yellow, and the essence is one or more of osmanthus fragrans essential oil, lemon essence and orange essence.
According to another aspect of the present invention, there is also provided a preparation method of the flurbiprofen sodium gel preparation, comprising the following steps:
1) adding the matrix into water, fully swelling, adding a pH regulator, and stirring to obtain a gel matrix;
2) adding the preservative, the percutaneous absorption enhancer and the flurbiprofen sodium into the solvent, dissolving, adding into the gel matrix, and uniformly stirring to obtain the flurbiprofen sodium gel preparation.
According to another aspect of the invention, the flurbiprofen sodium gel preparation is also provided for anti-inflammation, antipyretic and analgesic use.
The flurbiprofen sodium gel preparation prepared by the invention 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 invention has simple prescription components and process, adopts the flurbiprofen sodium as the anti-inflammatory active component, has the saturation solubility of about 36mg/ml in water and is more than 1000 times higher than that of the flurbiprofen, and experiments show that the flurbiprofen is used as the raw material to prepare the gel, a large amount of organic solvent is consumed, about 40 percent of isopropanol is used as the solvent for preparing 1 percent of the specification, the water solubility of the flurbiprofen sodium is obviously improved, about 3 percent of the specification hydrogel (calculated by the flurbiprofen) can be prepared without using the organic solvent, the dosage of the organic solvent is obviously reduced, the environment is friendly, and the invention is suitable for industrial mass production;
3. the pH value of the gel preparation is adjusted to be alkalescent by the pH regulator, so that the viscosity of a gel matrix is moderate (if the viscosity of the matrix is proper after swelling and the gel preparation is in a gel state, the pH regulator does not need to be added), the active ingredient flurbiprofen sodium exists stably in an ion form and cannot be separated out, the pH regulator and the flurbiprofen sodium form an ion pair, the drug loading rate is greatly improved, the transdermal absorption effect of the active ingredient is good, the product quality is stable, and the flurbiprofen sodium gel meets the medicinal requirements.
4. The invention adopts flurbiprofen sodium as an active ingredient, researches show that when the flurbiprofen gel is prepared, the content of impurities in the gel preparation is increased when a substance containing hydroxyl is added into an auxiliary material, so that the selection of the auxiliary material containing hydroxyl needs to be avoided, the selection range of related auxiliary materials such as a percutaneous absorption penetration enhancer is greatly reduced, the situation can not be caused when the flurbiprofen sodium is selected, for example, menthol and peppermint oil are both the percutaneous absorption penetration enhancers containing the hydroxyl, experiments show that the flurbiprofen and menthol (or peppermint oil) are uniformly mixed according to the weight ratio of 1:1, and flurbiprofen menthyl ester is generated and remarkably increases along with time when a compatibility test of the raw and auxiliary materials is carried out. And the compatibility test of the raw materials and the auxiliary materials is carried out by using the flurbiprofen sodium and the menthol (or the dementholized peppermint oil), so that the flurbiprofen menthyl ester is not detected. In addition, the propylene glycol, the glycerol, the isopropanol and the like in the solvent all contain hydroxyl, so that the possibility of forming ester by the flurbiprofen is greatly increased, and the impurity content in the flurbiprofen gel preparation is increased, therefore, the invention widens the selection range of the auxiliary materials, and enterprises can select the auxiliary materials according to the price, the transportation convenience and the like of the auxiliary materials.
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FIG. 1 is a substance-related detection pattern of a 6-month stability sample of an 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 of flurbiprofen gel and flurbiprofen sodium gel
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 isolated rat skin was fixed on a vertical Franz diffusion cell with a skin receiving area of 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%.
The flurbiprofen sodium gel prepared in the following examples 2 to 8 is analyzed for transdermal absorption performance, pharmacodynamics, skin irritation, local allergy and the like, and when the flurbiprofen sodium gel preparation is actually produced, a proper amount of surfactant, pigment or essence can be added according to needs without affecting the performance of the gel preparation.
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 dementholized peppermint oil, stirring for 10 minutes, adding 1000g of water, adding 50g of flurbiprofen sodium, dissolving, adding into a gel matrix, stirring for 30 minutes to obtain flurbiprofen sodium gel, and measuring the pH value to be 8.6.
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 methylparaben, 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 to obtain the flurbiprofen sodium gel, wherein the measured pH value is 7.1.
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, stirring for 30 minutes to obtain the flurbiprofen sodium gel, and measuring the pH value to be 7.2.
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, stirring for 30 minutes to obtain the flurbiprofen sodium gel, and measuring the pH value to be 7.1.
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, stirring for 30 minutes to obtain the flurbiprofen sodium gel, and measuring the pH value to be 7.2.
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, stirring for 30 minutes to obtain the flurbiprofen sodium gel, and measuring the pH value to be 7.6.
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, stirring for 30 minutes to obtain a gel matrix, adding 1000g of isopropanol, 5g of ethylparaben, 5g of propylparaben, 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, stirring for 30 minutes to obtain flurbiprofen sodium gel, and measuring the pH value to be 8.2.
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 applying on skin, and adding phosphorus at 32 deg.C and pH7.4And (3) taking the acid salt buffer solution as a receiving solution, completely taking out the receiving solution at 0.5, 1, 2, 4 and 6 hours respectively to measure the content, supplementing the receiving solution at 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 characteristics, 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 6-month long-term test 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%)
According to the stability research result, the flurbiprofen sodium gel prepared by the method has good stability, and all detection items are not obviously changed.
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 preparation is characterized by comprising the following components in percentage by weight:
0.5-5% of flurbiprofen sodium, 0.5-5% of matrix, 50-95% of solvent, 0-5% of pH regulator, 0.1-20% of percutaneous absorption penetration enhancer and 0.1-1.0% of preservative.
2. The flurbiprofen sodium gel formulation according to claim 1,
1.2-5% of flurbiprofen sodium, 0.8-4% of matrix, 70-95% of solvent, 0-4% of pH regulator, 0.1-10% of percutaneous absorption promoter and 0.1-0.5% of preservative.
3. The flurbiprofen sodium gel formulation according to claim 1 or 2,
the pH regulator is one or more of triethanolamine, diethanolamine, tromethamine, sodium hydroxide and triethylamine, preferably one or two of triethanolamine and tromethamine.
4. The flurbiprofen sodium gel formulation according to claim 3,
the flurbiprofen sodium gel preparation is alkaline, and the pH value is not more than 9.
5. The flurbiprofen sodium gel formulation according to claim 1 or 2,
the solvent is one or more of isopropanol, glycerol, propylene glycol, ethanol and purified water.
6. The flurbiprofen sodium gel formulation according to claim 1 or 2,
the solvent comprises water and a non-aqueous solvent, and the mass ratio of the water to the non-aqueous solvent is as follows: 1:1 to 10:1 of the total weight of the composition,
the water is purified water, and the non-aqueous solvent is one or more of isopropanol, glycerol, propylene glycol and ethanol.
7. The flurbiprofen sodium gel formulation according to claim 1 or 2,
the percutaneous absorption penetration enhancer is one or more of menthol, dementholized peppermint oil, laurocapram, N-methylpyrrolidone, isopropyl myristate, and crotamiton.
8. The flurbiprofen sodium gel formulation according to claim 1 or 2,
the matrix is one or more of carbomer, hydroxypropyl methylcellulose and sodium carboxymethylcellulose,
the antiseptic is one or more of methyl hydroxybenzoate, ethylparaben, propyl hydroxybenzoate, benzoic acid, sodium benzoate, chlorhexidine acetate, thimerosal, and phenoxyethanol.
9. A method for preparing a flurbiprofen sodium gel formulation as claimed in any one of claims 1 to 8, which comprises the steps of:
1) adding the matrix into water, fully swelling, adding a pH regulator, and stirring to obtain a gel matrix;
2) adding the preservative, the percutaneous absorption enhancer and the flurbiprofen sodium into the solvent, dissolving, adding into the gel matrix, and uniformly stirring to obtain the flurbiprofen sodium gel preparation.
10. Use of the flurbiprofen sodium gel formulation according to any one of claims 1 to 8 for anti-inflammatory, antipyretic and analgesic use.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| CN114939103A (en) * | 2022-05-27 | 2022-08-26 | 辽宁方诺生物科技有限公司 | Indometacin gel and preparation method and application 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 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN114939103A (en) * | 2022-05-27 | 2022-08-26 | 辽宁方诺生物科技有限公司 | Indometacin gel and preparation method and application thereof |
| CN114939103B (en) * | 2022-05-27 | 2023-11-17 | 辽宁方诺生物科技有限公司 | Indometate Xin Ningjiao agent and preparation method and application 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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