CN115887355A - Kelibuo cream and preparation method thereof - Google Patents
Kelibuo cream and preparation method thereof Download PDFInfo
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- CN115887355A CN115887355A CN202211446507.0A CN202211446507A CN115887355A CN 115887355 A CN115887355 A CN 115887355A CN 202211446507 A CN202211446507 A CN 202211446507A CN 115887355 A CN115887355 A CN 115887355A
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- 239000006071 cream Substances 0.000 title claims abstract description 64
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 9
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 9
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 239000003755 preservative agent Substances 0.000 claims abstract description 7
- 230000002335 preservative effect Effects 0.000 claims abstract description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 36
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 27
- 239000012071 phase Substances 0.000 claims description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 10
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 8
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 8
- -1 polyoxyethylene stearate Polymers 0.000 claims description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 6
- 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 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 6
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 6
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 claims description 6
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 6
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims description 6
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims description 6
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 6
- 229940057995 liquid paraffin Drugs 0.000 claims description 6
- WHRZCXAVMTUTDD-UHFFFAOYSA-N 1h-furo[2,3-d]pyrimidin-2-one Chemical compound N1C(=O)N=C2OC=CC2=C1 WHRZCXAVMTUTDD-UHFFFAOYSA-N 0.000 claims description 5
- 235000006173 Larrea tridentata Nutrition 0.000 claims description 5
- 244000073231 Larrea tridentata Species 0.000 claims description 5
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 5
- 229960002126 creosote Drugs 0.000 claims description 5
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 claims description 4
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 4
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 4
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 229960000541 cetyl alcohol Drugs 0.000 claims description 4
- 229940008099 dimethicone Drugs 0.000 claims description 4
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 4
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 4
- 229940075529 glyceryl stearate Drugs 0.000 claims description 4
- 229940100242 glycol stearate Drugs 0.000 claims description 4
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003002 pH adjusting agent Substances 0.000 claims description 4
- 229940056211 paraffin Drugs 0.000 claims description 4
- 239000012188 paraffin wax Substances 0.000 claims description 4
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 4
- 229940012831 stearyl alcohol Drugs 0.000 claims description 4
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 4
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 4
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 3
- 239000008346 aqueous phase Substances 0.000 claims description 3
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 claims description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004166 Lanolin Substances 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 150000005215 alkyl ethers Chemical class 0.000 claims description 2
- 230000002421 anti-septic effect Effects 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 2
- 229960004217 benzyl alcohol Drugs 0.000 claims description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 claims description 2
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 claims description 2
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 claims description 2
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 229940039717 lanolin Drugs 0.000 claims description 2
- 235000019388 lanolin Nutrition 0.000 claims description 2
- 239000000787 lecithin Substances 0.000 claims description 2
- 229940067606 lecithin Drugs 0.000 claims description 2
- 235000010445 lecithin Nutrition 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 229950008882 polysorbate Drugs 0.000 claims description 2
- 239000000473 propyl gallate Substances 0.000 claims description 2
- 235000010388 propyl gallate Nutrition 0.000 claims description 2
- 229940075579 propyl gallate Drugs 0.000 claims description 2
- 229940083037 simethicone Drugs 0.000 claims description 2
- 229940032094 squalane Drugs 0.000 claims description 2
- 229960004274 stearic acid Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 229940099259 vaseline Drugs 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims 1
- 239000000839 emulsion Substances 0.000 claims 1
- 239000000194 fatty acid Substances 0.000 claims 1
- 229930195729 fatty acid Natural products 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 229940114926 stearate Drugs 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 5
- 230000007794 irritation Effects 0.000 abstract description 4
- 208000003251 Pruritus Diseases 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- 230000007803 itching Effects 0.000 abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 230000008859 change Effects 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 201000008937 atopic dermatitis Diseases 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- USZAGAREISWJDP-UHFFFAOYSA-N crisaborole Chemical compound C=1C=C2B(O)OCC2=CC=1OC1=CC=C(C#N)C=C1 USZAGAREISWJDP-UHFFFAOYSA-N 0.000 description 2
- 229950008199 crisaborole Drugs 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 101100296719 Caenorhabditis elegans pde-4 gene Proteins 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 1
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 1
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
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- 239000003112 inhibitor Substances 0.000 description 1
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- 238000004806 packaging method and process Methods 0.000 description 1
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- 150000003384 small molecules Chemical class 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
Images
Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a Kelibuo cream and a preparation method thereof. The external Keliboro cream for skin comprises the components of Keliboro, a solvent, an emulsifier, an oil phase, an antioxidant, a preservative, a water phase and a pH regulator, and the prepared cream is uniform, fine, difficult to crystallize, easy to coat, quick in effect taking, good in itching relieving effect, capable of improving the skin affinity of the cream and reducing the irritation to the skin, and easy for industrial production.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a Keliboro cream and a preparation method thereof.
Background
Crisabiole (Crisabiole) is a phosphodiesterase-4 (PDE 4) inhibitor. PDE4 is a key regulator of inflammatory cytokine production in Atopic Dermatitis (AD), acting primarily through degradation of cyclic adenosine monophosphate. The Cleprednol is a boron-containing small-molecule anti-inflammatory drug, and the action mechanism is not completely clarified. Both the critical phase III studies of kreb reached primary and secondary endpoints at 7 months 2015. The first line of long-term safety research results of kreb used for 10 months in 2015 show that kreb used intermittently for more than 12 months has good tolerance and safety.
Patent CN110464702A discloses a cream of Clibolol and a preparation method thereof, wherein a nonaqueous cream matrix material is adopted to prepare the Clibolol ointment so as to improve the solubility and the preparation stability of the Clibolol.
The marketed preparation of Cliborol is a cream (trade name: EUCRISA) and is administered 2 times a day. According to the characteristics of allergic dermatitis diseases, the clinical compliance of long-time continuous administration is poor, the cream is mainly an oily matrix, the greasy feeling on the surface of the skin after administration is strong, the cream is difficult to clean after contacting with clothes and the like, the clinical compliance is poor, the production process of the cream is complex, the heat treatment is required for the preparation and sub-packaging of the medicine, and a special packaging material is required. Kribolol has a tendency to crystallize out of the cream formulation disclosed in US 2016/0318955 A1, especially when present at relatively high concentrations (e.g., 2%). This in turn may lead to physical instability of the formulation. Therefore, the development of stable, effective and quality-controllable external preparation of the krebs is very important.
Disclosure of Invention
The invention provides a Kelibuo cream for external use on skin and a preparation method thereof, the ingredients comprise a water phase and a pH regulator, the prepared cream is uniform and fine, is easy to coat, has quick response and good itching relieving effect, can improve the skin affinity of the cream and reduce the irritation to the skin, and is easy for industrial production.
The invention adopts the following technical scheme: the krebs cream comprises the following components in parts by weight: 1 to 3 portions of Kelibuo, 4 to 5 portions of solvent, 10 to 30 portions of emulsifier, 5 to 10 portions of oil phase, 0.01 to 0.2 portion of antioxidant, 0.05 to 0.2 portion of preservative and 45 to 65 portions of water phase.
In some embodiments, the krebs cream, in parts by weight, comprises: 2 portions of Clibolol, 5 portions of solvent, 14 to 24 portions of emulsifier, 7 to 8 portions of oil phase, 0.05 to 0.15 portion of antioxidant, 0.1 to 0.15 portion of preservative and 49 to 60 portions of water phase.
In some embodiments, the creosote cream has an emulsifier selected from one or more of glyceryl monostearate, polysorbate, polyoxyethylene stearate, polyoxyethylene alkyl ether, polyethylene glycol stearate, glyceryl stearate, cetyl alcohol, stearyl alcohol, poloxamer; preferably one or more of polyethylene glycol stearate, glyceryl mono-and distearate and glyceryl stearate.
In some embodiments, the oil phase in the kreb's cream is selected from one or more of liquid paraffin, solid paraffin, vaseline, dimethicone, fatty glyceride, lanolin, lecithin, squalane, stearic acid, cetyl alcohol, stearyl alcohol; preferably one or more of liquid paraffin, solid paraffin and simethicone; more preferably one or more of liquid paraffin and dimethicone.
In some embodiments, the antioxidant in the creboroxine cream is selected from one or more of disodium edetate, dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, and tert-butylhydroquinone; preferably one or more of disodium ethylene diamine tetraacetate, butylated hydroxytoluene and tertiary butyl hydroquinone; more preferably one or more of disodium edetate and dibutylhydroxytoluene.
In some embodiments, the crelibron cream has one or more preservatives selected from ethylparaben, parabens, phenol, benzyl alcohol, benzoic acid, and the like; preferably ethylparaben or phenol; more preferably ethylparaben.
In some embodiments, the aqueous phase of the krebs cream is selected from one or more of water, propylene glycol, diethylene glycol monoethyl ether, glycerol, and isopropanol; preferably one or more of water, propylene glycol, diethylene glycol monoethyl ether or glycerol; more preferably a combination of water, propylene glycol and diethylene glycol monoethyl ether.
In some embodiments, the solvent in the creborole cream is selected from one or more of ethanol, propylene glycol, glycerol, isopropanol, benzyl alcohol; preferably one or more of propylene glycol or glycerol.
In some embodiments, the creborole cream further comprises a pH adjusting agent selected from one or more of sodium hydroxide, triethanolamine, hydrochloric acid; preferably triethanolamine or sodium hydroxide, the pH of the creosote is adjusted to 4 to 7, more preferably to 5 to 6, by adding a pH adjusting agent.
In some exemplary embodiments, the krebs cream comprises the following components by weight:
in some exemplary embodiments, the krebs cream comprises the following components by weight:
the invention also provides a preparation method of the krebs cream, which comprises the following steps:
(a) Respectively weighing emulsifier, oil phase, antioxidant and antiseptic, mixing, and heating to 80 deg.C;
(b) Dissolving API in solvent at 50-55 deg.C;
(c) Under the condition of stirring, adding the mixture obtained in the step (a) into an aqueous phase, reducing the temperature of the mixture to 55-60 ℃, adding the solution obtained in the step (b), and continuing stirring and reducing the temperature;
(d) Cooling to room temperature, and adjusting pH to 5-6 with pH regulator;
the invention has the beneficial effects that: the Kelibuo cream for external use on skin provided by the invention is uniform, fine, difficult to crystallize, easy to coat, quick in effect taking, good in itching relieving effect, capable of improving the skin affinity of the cream and reducing the irritation to the skin, and easy for industrial production.
Drawings
FIG. 1 is a diagram showing properties observed under an electron microscope in example 1;
FIG. 2 is a diagram showing the behavior observed under an electron microscope in example 2;
FIG. 3 is a graph showing the behavior observed under an electron microscope in example 3;
FIG. 4 graph of rheological profile change for example 2;
FIG. 5 graph of the change in rheological properties of example 3;
figure 6 graph of the change in rheological properties of the reference formulation.
Detailed description of the preferred embodiments
The present invention is further described with reference to specific examples to enable those skilled in the art to better understand the present invention and to practice the same, but the examples are not intended to limit the present invention.
Example 1
Formula of cream 1
Preparation process of cream 1:
(a) All ingredients in phases 1, 2 were weighed separately and then heated to 80 ℃;
(b) Dissolving API in propylene glycol at 50-55 deg.C;
(c) Adding phase 1 into phase 2 under stirring, adding phase 3 when the temperature of the mixture is about 55-60 deg.C, and continuing stirring for cooling;
(d) And (5) cooling to room temperature, and adjusting the pH value to be between 5 and 6.
Observing the shape of the obtained cream under an optical microscope, respectively placing the cream at 40 ℃ and 60 ℃ for 10 days, taking out, cooling to room temperature, and inspecting the property change of the cream. See figure 1 and table 1 below for the results.
Example 2
Formula of cream 2
Preparation process of cream 2:
(a) All ingredients in phases 1, 2 were weighed separately and then heated to 80 ℃;
(b) Dissolving API in propylene glycol at 50-55 deg.C;
(c) Adding phase 1 into phase 2 under stirring, adding phase 3 when the mixture temperature is about 55-60 deg.C, and continuing stirring and cooling;
(d) And (5) cooling to room temperature, and adjusting the pH value to be between 4 and 6.
Observing the shape of the obtained cream under an optical microscope, respectively placing the cream at 40 ℃ and 60 ℃ for 10 days, taking out, cooling to room temperature, and inspecting the property change of the cream. See figure 2 and table 1 below for the results.
Example 3
Formula of cream 3
Preparation process of cream 3:
(a) All ingredients in phases 1, 2 were weighed separately and then heated to 80 ℃;
(b) Dissolving API in glycerol at 50-55 deg.C;
(c) Adding phase 1 into phase 2 under stirring, adding phase 3 when the temperature of the mixture is about 55-60 deg.C, and continuing stirring and cooling;
(d) And (5) cooling to room temperature, and adjusting the pH value to be between 5 and 6.
Observing the shape of the obtained cream under an optical microscope, respectively placing the cream at 40 ℃ and 60 ℃ for 10 days, taking out the cream, cooling to room temperature, and inspecting the property change of the cream. See figure 3 and table 1 below for results.
TABLE 1 Property changes of creams of different formulations
Test example
The results of examining the finished product characteristics, centrifugation and thermal cycle tests of the self-prepared product prepared in the above examples, commercially available krebs ointment (trade name: eurisa) and example 3 in patent CN110464702A (hereinafter referred to as comparative example 1) show that the ointments of examples 2 and 3 have uniform particle size distribution, are easy to spread, have no irritation to skin and have stable physical properties, and the results are as follows:
accelerated stability tests were conducted on the self-products obtained in examples 2 to 3, commercially available krebs ointment (trade name: EUCRISA) and comparative example 1, and samples were taken at 1 month, 3 months and 6 months to determine properties, content uniformity and impurities, and the results are shown in the following table.
The results show that: the crystallization phenomenon does not occur in the examples 2 and 3 under the accelerated condition for 6 months, the content, the maximum single impurity and the total impurity are obviously lower than those of the reference preparation and the comparative example 1, and the quality is better than that of the reference preparation and the comparative example 1.
Claims (10)
1. The krebs cream comprises the following components in parts by weight: 1 to 3 portions of Clibotuo, 4 to 5 portions of solvent, 10 to 30 portions of emulsifier, 5 to 10 portions of oil phase, 0.01 to 0.2 portion of antioxidant, 0.05 to 0.2 portion of preservative and 45 to 65 portions of water phase.
2. The krebs cream of claim 1, which comprises, in parts by weight: 2 portions of Clibolol, 5 portions of solvent, 14 to 24 portions of emulsifier, 7 to 8 portions of oil phase, 0.05 to 0.15 portion of antioxidant, 0.1 to 0.15 portion of preservative and 49 to 60 portions of water phase.
3. The creosote cream of claims 1-2, wherein the creosote emulsion comprises an emulsifier selected from one or more of glyceryl monostearate, polysorbate, polyoxyethylene stearate, polyoxyethylene alkyl ether, polyethylene glycol stearate, glyceryl stearate, cetyl alcohol, stearyl alcohol, poloxamer; preferably one or more of polyethylene glycol stearate, glyceryl mono-bis stearate and glyceryl stearate.
4. Keliborong cream according to claims 1-2, characterised in that the oily phase of the Keliborong cream is selected from one or more of liquid paraffin, solid paraffin, vaseline, dimethicone, fatty acid glyceride, lanolin, lecithin, squalane, stearic acid, cetyl alcohol, stearyl alcohol; preferably one or more of liquid paraffin, solid paraffin and simethicone; more preferably one or more of liquid paraffin and dimethicone; preferably, the antioxidant in the kreb cream is selected from one or more of disodium ethylenediamine tetraacetate, dibutyl hydroxy toluene, butyl hydroxy anisole, propyl gallate and tert-butyl hydroquinone; preferably one or more of disodium ethylene diamine tetraacetate, butylated hydroxytoluene and tertiary butyl hydroquinone; more preferably one or more of disodium edetate and dibutylhydroxytoluene.
5. A Keliborong cream as claimed in claims 1 to 2, wherein the preservatives in the Keliborong cream are selected from one or more of ethylparaben, parabens, phenol, benzyl alcohol, benzoic acid, etc.; preferably ethylparaben or phenol; more preferably ethylparaben; preferably, the water phase in the kreb cream is selected from one or more of water, propylene glycol, diethylene glycol monoethyl ether, glycerol and isopropanol; preferably one or more of water, propylene glycol, diethylene glycol monoethyl ether or glycerol; more preferably a combination of water, propylene glycol and diethylene glycol monoethyl ether.
6. The kreb cream as claimed in claim 1-2, wherein the kreb cream has a solvent selected from one or more of ethanol, propylene glycol, glycerol, isopropanol, and benzyl alcohol; preferably one or more of propylene glycol or glycerol.
7. The kreb cream as claimed in claims 1-2, wherein the kreb cream further comprises a pH adjusting agent selected from one or more of sodium hydroxide, triethanolamine, hydrochloric acid; preferably triethanolamine or sodium hydroxide, the pH of the creosote is adjusted to 4 to 7, more preferably to 5 to 6, by adding a pH adjusting agent.
8. Kreb cream according to claims 1-2, characterized by comprising the following components by weight:
9. krebs cream according to claims 1-2, characterized by comprising the following components by weight:
10. a process for the preparation of krebs cream as claimed in claims 1-2, comprising the steps of:
(a) Respectively weighing emulsifier, oil phase, antioxidant and antiseptic, mixing, and heating to 80 deg.C;
(b) Dissolving API in solvent at 50-55 deg.C;
(c) Under the condition of stirring, adding the mixture obtained in the step (a) into an aqueous phase, reducing the temperature of the mixture to 55-60 ℃, adding the solution obtained in the step (b), and continuing stirring and reducing the temperature;
(d) And (5) cooling to room temperature, and adjusting the pH value to 5-6 by using a pH regulator.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202211446507.0A CN115887355A (en) | 2022-11-18 | 2022-11-18 | Kelibuo cream and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202211446507.0A CN115887355A (en) | 2022-11-18 | 2022-11-18 | Kelibuo cream and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010095091A1 (en) * | 2009-02-18 | 2010-08-26 | Sulur Subramaniam Vanangamudi | A process to make fusidic acid cream |
| CN113712977A (en) * | 2020-05-25 | 2021-11-30 | 南京帝昌医药科技有限公司 | Cliboroluo external preparation and preparation method and application thereof |
| CN113797159A (en) * | 2021-10-22 | 2021-12-17 | 冠昊生物科技股份有限公司 | Vatinuomod cream and preparation method and application thereof |
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2022
- 2022-11-18 CN CN202211446507.0A patent/CN115887355A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010095091A1 (en) * | 2009-02-18 | 2010-08-26 | Sulur Subramaniam Vanangamudi | A process to make fusidic acid cream |
| CN113712977A (en) * | 2020-05-25 | 2021-11-30 | 南京帝昌医药科技有限公司 | Cliboroluo external preparation and preparation method and application thereof |
| CN113797159A (en) * | 2021-10-22 | 2021-12-17 | 冠昊生物科技股份有限公司 | Vatinuomod cream and preparation method and application thereof |
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