CN118121535A - Compound ketoconazole gel and preparation method thereof - Google Patents
Compound ketoconazole gel and preparation method thereof Download PDFInfo
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- CN118121535A CN118121535A CN202410252384.XA CN202410252384A CN118121535A CN 118121535 A CN118121535 A CN 118121535A CN 202410252384 A CN202410252384 A CN 202410252384A CN 118121535 A CN118121535 A CN 118121535A
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- ketoconazole
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- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 title claims abstract description 84
- 229960004125 ketoconazole Drugs 0.000 title claims abstract description 83
- 150000001875 compounds Chemical class 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000001879 gelation Methods 0.000 title description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 71
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 63
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 31
- 229960001631 carbomer Drugs 0.000 claims abstract description 31
- 235000011187 glycerol Nutrition 0.000 claims abstract description 31
- 229920001519 homopolymer Polymers 0.000 claims abstract description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 25
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 claims abstract description 21
- 229960004703 clobetasol propionate Drugs 0.000 claims abstract description 21
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims abstract description 21
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229940101006 anhydrous sodium sulfite Drugs 0.000 claims abstract description 20
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims abstract description 20
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims abstract description 19
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims abstract description 19
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims abstract description 19
- 239000008213 purified water Substances 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 150000002576 ketones Chemical class 0.000 claims abstract description 15
- 235000017858 Laurus nobilis Nutrition 0.000 claims abstract description 13
- 244000125380 Terminalia tomentosa Species 0.000 claims abstract description 13
- 235000005212 Terminalia tomentosa Nutrition 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 13
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims abstract description 10
- 229940124274 edetate disodium Drugs 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims description 72
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- 230000008961 swelling Effects 0.000 claims description 16
- 230000001804 emulsifying effect Effects 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 14
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 11
- 241000289690 Xenarthra Species 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 239000011159 matrix material Substances 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 7
- 239000011259 mixed solution Substances 0.000 claims description 6
- 238000004321 preservation Methods 0.000 claims description 4
- 229960004827 anhydrous edetate disodium Drugs 0.000 claims description 3
- 235000013772 propylene glycol Nutrition 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 2
- 229960005150 glycerol Drugs 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 238000002156 mixing Methods 0.000 abstract description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 7
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229960003639 laurocapram Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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- 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
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Abstract
The invention provides a compound ketoconazole gel and a preparation method thereof, wherein the compound ketoconazole gel comprises 1 to 10 parts of ketoconazole according to parts; 0.1 to 3 parts of clobetasol propionate; 5-20 parts of carbomer homopolymer; 5-20 parts of triethanolamine; laurel nitrogen
Description
Technical Field
The invention relates to the technical field of chemical medicines, in particular to a compound ketoconazole gel and a preparation method thereof.
Background
Ketoconazole (CAS: 65277-42-1) is an imidazole broad-spectrum antifungal agent, widely used as a skin external compound for the treatment of various skin fungal infections. However, since the oral preparation of ketoconazole is liable to cause serious liver injury, the production of the oral preparation of ketoconazole has been stopped in 2015 by the food and drug administration of China, and the existing various external medicines containing ketoconazole, such as compound ketoconazole lotion, compound ketoconazole ointment and ketoconazole cream, have been called out of OTC medicine catalogue
In the prior art, in the process of preparing ketoconazole ointment, the solubility of ketoconazole in absolute ethyl alcohol is low, and when the solubility of ketoconazole is improved, the adhesiveness and stability of ketoconazole are reduced, and the preparation cost is increased.
Disclosure of Invention
Based on the above, the present invention aims to provide a compound ketoconazole gel and a preparation method thereof, so as to at least solve the above-mentioned shortcomings in the prior art.
In a first aspect, the invention provides a compound ketoconazole gel, which is characterized by comprising the following components in parts by weight:
1 to 10 parts of ketoconazole;
0.1 to 3 parts of clobetasol propionate;
5-20 parts of carbomer homopolymer;
5-20 parts of triethanolamine;
Laurel nitrogen 5-50 Parts of ketone;
40-70 parts of absolute ethyl alcohol;
40-70 parts of glycerol;
10-50 parts of propylene glycol;
1 to 5 parts of ethylparaben;
1 to 5 parts of anhydrous sodium sulfite;
0.1 to 2 parts of edetate disodium;
1000-1200 parts of purified water.
Compared with the prior art, the invention has the beneficial effects that: the main medicine of the compound ketoconazole gel is formed by mixing the ethylparaben, ketoconazole, clobetasol propionate and glycerin, so that the dissolving capacity of ketoconazole in absolute ethyl alcohol is effectively improved, the production cost can be effectively reduced, and the stability of the compound ketoconazole gel can be maintained by the cooperation of carbomer homopolymer, triethanolamine, absolute ethyl alcohol, propylene glycol, anhydrous sodium sulfite, disodium edetate, ethylparaben, clobetasol propionate and glycerin.
In a second aspect, the present invention provides a method for preparing a compound ketoconazole gel, for preparing the compound ketoconazole gel, the method comprising:
Adding a first preset amount of purified water into a swelling tank, and adding a carbomer homopolymer to perform first stirring to obtain a swelling carbomer homopolymer;
Glycerin, propylene glycol and laurel nitrogen Putting the ketone into a liquid preparation tank, and stirring for the second time to obtain a liquid preparation mixture;
adding a second preset amount of purified water into a batching bucket, adding anhydrous sodium sulfite and edetate disodium into the batching bucket, and stirring for the third time to obtain a batching mixture;
adding the swelling carbomer homopolymer into an emulsifying tank for fourth stirring, adding the liquid mixture and the burdening mixture into the emulsifying tank for fifth stirring, and adding triethanolamine into the emulsifying tank for sixth stirring to obtain a transparent gel matrix;
Adding the ethylparaben, the ketoconazole, the clobetasol propionate and the glycerol into absolute ethyl alcohol, heating and stirring, and carrying out heat preservation and stirring to obtain a main medicine mixed solution;
and adding the main medicine mixed solution into the transparent gel matrix, and carrying out seventh stirring to obtain the compound ketoconazole gel.
Further, after the step of adding the carbomer homopolymer and performing a first stirring to obtain a swollen carbomer homopolymer, the method comprises the following steps:
stopping the first stirring and subjecting the swollen carbomer homopolymer to stationary swelling.
Further, the time of the first stirring is 5-10 minutes.
Further, the step of performing the second stirring to obtain a liquid mixture comprises the following steps:
For the glycerin, the propylene glycol, and the laurel nitrogen Stirring the ketone for 5 to 10 minutes to stir the glycerin, the propylene glycol and the laurel nitrogen/>The ketone is thoroughly mixed.
Further, the step of stirring for the third time to obtain the ingredient mixture comprises the following steps:
and stirring the anhydrous sodium sulfite and the disodium edentate for the third time so as to completely dissolve the anhydrous sodium sulfite and the disodium edentate.
Further, the fifth stirring time is 30-60 minutes.
Further, the step of adding triethanolamine into the emulsifying tank and stirring for the sixth time to obtain the transparent gel matrix comprises the following steps:
And adding the triethanolamine into the emulsifying tank to perform a sixth stirring, wherein the sixth stirring is slow stirring for 30-35 minutes, so as to obtain the transparent gel matrix.
Further, the temperature of the heating and stirring is 40-60 ℃.
Further, the seventh stirring is performed at a slow speed, and the time of the seventh stirring is 10-70 minutes.
Detailed Description
Example 1
A compound ketoconazole gel comprises 1 part of ketoconazole, 0.1 part of clobetasol propionate, 5 parts of carbomer homopolymer, 5 parts of triethanolamine and laurocapram by weight5 Parts of ketone, 40 parts of absolute ethyl alcohol, 40 parts of glycerin, 10 parts of propylene glycol, 1 part of ethylparaben, 1 part of anhydrous sodium sulfite, 0.1 part of disodium edentate and 1000 parts of purified water.
It should be explained that the main medicine of the compound ketoconazole gel is formed by mixing the ethylparaben, ketoconazole, clobetasol propionate and glycerin, so that the dissolution capacity of ketoconazole in absolute ethyl alcohol is effectively improved, the production cost can be effectively reduced, and the stability of the compound ketoconazole gel can be maintained by the cooperation of carbomer homopolymer, triethanolamine, absolute ethyl alcohol, propylene glycol, anhydrous sodium sulfite, disodium edetate, ethylparaben, clobetasol propionate and glycerin.
The preparation method of the compound ketoconazole gel comprises the steps of S1 to S6:
S1, adding a first preset amount of purified water into a swelling tank, and adding carbomer homopolymer to perform first stirring to obtain a swelling carbomer homopolymer;
Specifically, after the swollen carbomer homopolymer is obtained, stirring is stopped, and the swollen carbomer homopolymer is subjected to stationary swelling to obtain a stable swollen carbomer homopolymer, in this embodiment, the first stirring time is 5 minutes, the first preset amount of purified water is 1 part, in other alternative embodiments, the first stirring time is selectable in the range of 5 to 10 minutes, and the first preset amount of purified water is selectable in the range of 1 to 2 parts.
S2, glycerin, propylene glycol and laurel nitrogen are addedPutting the ketone into a liquid preparation tank, and stirring for the second time to obtain a liquid preparation mixture;
specifically, the glycerin, propylene glycol and laurocapram put into the liquid preparation tank are subjected to second stirring so that the glycerin, propylene glycol and laurocapram are fully mixed to obtain a liquid preparation mixture, in this embodiment, the second stirring time is 5 minutes, and in other alternative embodiments, the second stirring time is selected in the range of 5-10 minutes.
S3, adding a second preset amount of purified water into a batching bucket, adding anhydrous sodium sulfite and edetate disodium into the batching bucket, and stirring for the third time to obtain a batching mixture;
Specifically, in this embodiment, the second preset amount of purified water is 9 parts, and in other alternative embodiments, the second preset amount of purified water is optional in a range of 9-10 parts, and it should be explained that, in specific implementation, anhydrous sodium sulfate and disodium edentate are slowly added into the batching bucket, and then the third stirring is performed until the anhydrous sodium sulfite and disodium edentate are completely dissolved.
S4, adding the swelling carbomer homopolymer into an emulsifying tank for fourth stirring, adding the liquid mixture and the burdening mixture into the emulsifying tank for fifth stirring, and adding triethanolamine into the emulsifying tank for sixth stirring to obtain a transparent gel matrix;
Specifically, the swelling carbomer homopolymer is stirred in the emulsifying tank for a fourth time, the fourth time is stirred slowly, then the liquid mixture and the mixture are added into the emulsifying tank for a fifth time, in this embodiment, the fifth time is 30 minutes, the sixth time is 30 minutes, in other alternative embodiments, the fifth time is selected from the range of 30 to 60 minutes.
S5, adding the ethylparaben, the ketoconazole, the clobetasol propionate and the glycerol into absolute ethyl alcohol, heating and stirring, and carrying out heat preservation and stirring to obtain a main medicine mixed solution;
Specifically, ethyl hydroxybenzoate, ketoconazole, clobetasol propionate and glycerin are slowly added into absolute ethyl alcohol to be heated and stirred, in the embodiment, the temperature of the heating and stirring is 40 ℃, in other alternative embodiments, the temperature of the heating and stirring is selectable within the range of 40-60 ℃, and then the heat preservation and stirring are carried out until the ethyl hydroxybenzoate, ketoconazole, clobetasol propionate, glycerin and absolute ethyl alcohol are completely dissolved.
S6, adding the main medicine mixed solution into the transparent gel matrix, and carrying out seventh stirring to obtain compound ketoconazole gel;
Specifically, in this embodiment, the seventh stirring time is 10 minutes, and in other alternative embodiments, the seventh stirring time is selected in the range of 10 to 70 minutes.
Example two
The present embodiment is different from the first embodiment in that:
The weight of ketoconazole in the compound ketoconazole gel is 3 parts, clobetasol propionate 0.2 parts, carbomer homopolymer 7 parts, triethanolamine 8 parts and laurocapram 10 Parts of ketone, 50 parts of absolute ethyl alcohol, 50 parts of glycerin, 20 parts of propylene glycol, 2 parts of ethylparaben, 2 parts of anhydrous sodium sulfite, 0.8 part of disodium edentate and 1100 parts of purified water.
Example III
The present embodiment is different from the above embodiment in that:
the weight of ketoconazole in the compound ketoconazole gel is 5 parts, the clobetasol propionate is 1 part, the carbomer homopolymer is 14 parts, the triethanolamine is 15 parts, and the laurel nitrogen is 1 part 30 Parts of ketone, 60 parts of absolute ethyl alcohol, 60 parts of glycerin, 40 parts of propylene glycol, 4 parts of ethylparaben, 4 parts of anhydrous sodium sulfite, 1.4 parts of disodium edentate and 1150 parts of purified water.
Example IV
The weight of ketoconazole in the compound ketoconazole gel is 7 parts, the clobetasol propionate is 2 parts, the carbomer homopolymer is 16 parts, the triethanolamine is 18 parts, and the laurel nitrogen is the same as the total weight of the ketoconazole gel40 Parts of ketone, 65 parts of absolute ethyl alcohol, 65 parts of glycerin, 45 parts of propylene glycol, 4.5 parts of ethylparaben, 4.5 parts of anhydrous sodium sulfite, 1.8 parts of disodium edentate and 1150 parts of purified water.
Example five
The compound ketoconazole gel comprises 5 parts by weight of ketoconazole, 3 parts by weight of clobetasol propionate, 20 parts by weight of carbomer homopolymer, 20 parts by weight of triethanolamine and laurel nitrogen50 Parts of ketone, 70 parts of absolute ethyl alcohol, 70 parts of glycerin, 50 parts of propylene glycol, 5 parts of ethylparaben, 5 parts of anhydrous sodium sulfite, 2 parts of disodium edentate, 12 parts of purified water and 1200 parts of purified water.
Comparative example 1
According to the preparation method of the first embodiment, the weight of ketoconazole is 15 parts.
Comparative example 2
According to the preparation method of the first embodiment, the weight of ketoconazole is 20 parts.
The compound ketoconazole obtained in the examples and the comparative examples is applied to mice, coated on the skin of the mice, and the experimental animals are mice, and the back of the mice has the phenomena of redness and swelling and abnormal spots.
The back of the mice was shaved with a razor, the hair on the back of the mice was removed with a dehairing wax, and the back of the mice was made to form two 2cm×2cm hairless areas, and the compound ketoconazole gel prepared in each of the above examples and comparative examples was applied to the hairless areas, and after one application, observation was continued for one week, and each compound ketoconazole gel was scored with one sentence of the cases on the hairless areas of the back of the mice.
The scoring criteria were:
1, the method comprises the following steps: the whole skin is red and swollen and has abnormal spots;
2, the method comprises the following steps: the red and swollen part of the skin accounts for seventy percent of the whole piece of skin, and abnormal spots exist;
3, the method comprises the following steps: reddish and swelling of the skin, and the red area accounts for forty percent of the whole piece of skin, and a few abnormal spots exist;
4, the following steps: no swelling, reddish and no spots;
5, the method comprises the following steps: is not red, is not swollen, has no spots, and the skin is in a healthy state.
It is worth noting that each example and comparative example was smeared on at least two mice to avoid the occurrence of experimental contingency.
For specific experimental results, please refer to table 1:
TABLE 1
As can be seen from table 1, the skin of the back of the mice can be cured by changing the content of ketoconazole, and as can be seen from comparative examples one and two, the back of the mice can be treated when the content of ketoconazole is too high, while the content of ketoconazole in examples one to five is reduced compared with that in comparative examples one and two, but the solubility of ketoconazole in absolute ethyl alcohol is improved, so that the effect exerted by the ketoconazole is better, the effect is further effectively improved, the treatment effect of ketoconazole is not influenced, and the production cost is further effectively reduced.
And it is worth to say that, can promote the solubility of ketoconazole in absolute ethyl alcohol through adding the glycerol, reduce the temperature in the dissolution process, can reduce the play amount of absolute ethyl alcohol when being heated, promote the security of production, and the ketoconazole gel appearance that prepares is transparent, even fine and smooth, adhesion and stability are good.
In summary, the compound ketoconazole gel in the embodiment of the invention is prepared by mixing the main drugs of the compound ketoconazole gel with the ethylparaben, the ketoconazole, the clobetasol propionate and the glycerol, so that the dissolving capacity of ketoconazole in absolute ethyl alcohol is effectively improved, the production cost can be effectively reduced, and the stability of the compound ketoconazole gel can be maintained by the cooperation of carbomer homopolymer, triethanolamine, absolute ethyl alcohol, propylene glycol, anhydrous sodium sulfite, disodium edetate, ethylparaben, clobetasol propionate and the glycerol.
In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The foregoing examples illustrate only a few embodiments of the invention and are described in detail herein without thereby limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (10)
1. The compound ketoconazole gel is characterized by comprising the following components in parts by weight:
1 to 10 parts of ketoconazole;
0.1 to 3 parts of clobetasol propionate;
5-20 parts of carbomer homopolymer;
5-20 parts of triethanolamine;
Laurel nitrogen 5-50 Parts of ketone;
40-70 parts of absolute ethyl alcohol;
40-70 parts of glycerol;
10-50 parts of propylene glycol;
1 to 5 parts of ethylparaben;
1 to 5 parts of anhydrous sodium sulfite;
0.1 to 2 parts of edetate disodium;
1000-1200 parts of purified water.
2. A method for preparing a compound ketoconazole gel according to claim 1, said method comprising:
Adding a first preset amount of purified water into a swelling tank, and adding a carbomer homopolymer to perform first stirring to obtain a swelling carbomer homopolymer;
Glycerin, propylene glycol and laurel nitrogen Putting the ketone into a liquid preparation tank, and stirring for the second time to obtain a liquid preparation mixture;
adding a second preset amount of purified water into a batching bucket, adding anhydrous sodium sulfite and edetate disodium into the batching bucket, and stirring for the third time to obtain a batching mixture;
adding the swelling carbomer homopolymer into an emulsifying tank for fourth stirring, adding the liquid mixture and the burdening mixture into the emulsifying tank for fifth stirring, and adding triethanolamine into the emulsifying tank for sixth stirring to obtain a transparent gel matrix;
Adding the ethylparaben, the ketoconazole, the clobetasol propionate and the glycerol into absolute ethyl alcohol, heating and stirring, and carrying out heat preservation and stirring to obtain a main medicine mixed solution;
and adding the main medicine mixed solution into the transparent gel matrix, and carrying out seventh stirring to obtain the compound ketoconazole gel.
3. The method for preparing a compound ketoconazole gel according to claim 2, wherein after said step of adding carbomer homopolymer and performing a first stirring to obtain a swollen carbomer homopolymer, said method comprises:
stopping the first stirring and subjecting the swollen carbomer homopolymer to stationary swelling.
4. The method for preparing compound ketoconazole gel according to claim 2, wherein said first stirring time is 5-10 minutes.
5. The method for preparing compound ketoconazole gel according to claim 2, wherein said step of performing second stirring to obtain a liquid mixture comprises:
For the glycerin, the propylene glycol, and the laurel nitrogen Stirring the ketone for 5 to 10 minutes to stir the glycerin, the propylene glycol and the laurel nitrogen/>The ketone is thoroughly mixed.
6. The method for preparing a compound ketoconazole gel according to claim 2, wherein said step of stirring for the third time to obtain a mixture of ingredients comprises:
and stirring the anhydrous sodium sulfite and the disodium edentate for the third time so as to completely dissolve the anhydrous sodium sulfite and the disodium edentate.
7. The method for preparing compound ketoconazole gel according to claim 2, wherein the fifth stirring time is 30-60 minutes.
8. The method for preparing compound ketoconazole gel according to claim 2, wherein said step of adding triethanolamine into said emulsifying tank and stirring for the sixth time to obtain transparent gel matrix comprises:
And adding the triethanolamine into the emulsifying tank to perform a sixth stirring, wherein the sixth stirring is slow stirring for 30-35 minutes, so as to obtain the transparent gel matrix.
9. The method for preparing compound ketoconazole gel according to claim 2, wherein the temperature of heating and stirring is 40-60 ℃.
10. The method for preparing compound ketoconazole gel according to claim 2, wherein said seventh stirring is slow stirring, and the time of said seventh stirring is 10-70 minutes.
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