CN111012735A - Preparation method of emulsifiable paste under alkaline condition - Google Patents

Preparation method of emulsifiable paste under alkaline condition Download PDF

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Publication number
CN111012735A
CN111012735A CN201911235693.1A CN201911235693A CN111012735A CN 111012735 A CN111012735 A CN 111012735A CN 201911235693 A CN201911235693 A CN 201911235693A CN 111012735 A CN111012735 A CN 111012735A
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phase
water phase
heating
cream
fatty acid
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颜克序
戴信敏
赵维亮
王学智
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Beijing Xinkaiyuan Pharmaceuticals Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof

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  • Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Inorganic Chemistry (AREA)
  • Cosmetics (AREA)

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a cream under an alkaline condition, which comprises the following steps: c is to be11～C18Placing fatty acid and alkaline substance into the first water phase to obtain a second water phase; respectively heating the second water phase and the oil phase, and then carrying out isothermal mixing on the two phases to obtain a uniform emulsification system; and under the condition of stirring, cooling and solidifying the emulsifying system to obtain the cream. The preparation method of the cream under the alkaline condition has good stability on unstable components, an emulsifying system and the cream under the alkaline condition, and has good stability on the unstable components, the emulsifying system and the cream under the alkaline conditionEnhancing the using effect and stability of the medicine has important significance.

Description

Preparation method of emulsifiable paste under alkaline condition
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a cream under an alkaline condition.
Background
The ointment prepared from the emulsion matrix is called cream, and the cream is composed of oil phase and water phaseAnd an emulsifier, wherein the fatty acid salt anionic surfactant is a commonly used emulsifier in cream. Fatty acid means C11～C18Fatty acids such as commonly used synthetic stearic acid or natural vegetable oils containing various carboxylic acids, e.g., lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and the like; the fatty acid salt is typically a sodium, potassium, calcium, magnesium or triethanolamine salt of a fatty acid; these emulsifiers are usually formed during the emulsification process by adding suitable amounts of fatty acids and hydroxides of sodium, potassium, calcium, magnesium ions or triethanolamine; lipophilic fatty acid is generally melted (dissolved) in an oil phase according to physical properties, hydroxide of sodium, potassium, calcium, magnesium ions and triethanolamine are dissolved in an aqueous phase, and then the mixture is stirred at a proper temperature to form a stable emulsifying system, and the emulsifier generated in the mixing and stirring process also belongs to soap components, so the emulsifier is also called as a "soap emulsifier". In the process of preparing a cream medicament by using a soap emulsifier, active ingredients are often encountered, are unstable and easy to decompose under an alkaline condition, and are inevitably and directly contacted with alkaline substances such as hydroxides of sodium, potassium, calcium and magnesium ions in the emulsifying, mixing and stirring process no matter the active ingredients are placed in a water phase or an oil phase, so that the content of the active ingredients is reduced, and the medicament effect is influenced; in order to increase the stability of the medicine, a proper amount of preservative is often required to be added into the cream, and many ester preservatives are unstable under alkaline conditions and are decomposed in the mixing and stirring process, so that the preservative capability is reduced.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide a preparation method of a cream under alkaline conditions, aiming at improving the stability and the using effect of a medicine.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a preparation method of a cream under alkaline conditions, which comprises the following steps:
placing fatty acid and alkaline substance into the first water phase to obtain a second water phase, wherein the fatty acid comprises C11～C18Series of fatsAt least one of an acid;
respectively heating the second water phase and the oil phase, and then carrying out isothermal mixing on the two phases to obtain a uniform emulsification system;
and under the condition of stirring, cooling and solidifying the emulsifying system to obtain the cream.
In one embodiment, the step of placing the fatty acid and the basic material in a first aqueous phase to obtain a second aqueous phase comprises:
mixing a first aqueous phase and an alkaline substance to completely dissolve the alkaline substance;
and adding fatty acid into the first water phase, and stirring and heating to form uniform emulsion so as to obtain a second water phase.
In one embodiment, the step of adding fatty acid into the first aqueous phase and heating while stirring to form a uniform emulsion to obtain the second aqueous phase, wherein the heating temperature is 70-99 ℃.
In one embodiment, the first aqueous phase comprises at least one of glycerin, sodium carboxymethylcellulose, polyethylene glycol, sodium hydroxide, potassium hydroxide, calcium hydroxide, peregal, polysorbate, sodium lauryl sulfate, and water;
in one embodiment, the fatty acid comprises at least one of lauric acid, myristic acid, palmitic acid, stearic acid, and oleic acid;
in one embodiment, the alkaline substance comprises at least one of sodium hydroxide, potassium hydroxide, calcium hydroxide.
In one embodiment, the oil phase comprises at least one of cetyl alcohol, stearyl alcohol, cetostearyl alcohol, glycerin, liquid paraffin, petrolatum, monoglycerides, silicone oil, beeswax, and lanolin;
in one embodiment, the step of separately heating the second aqueous phase and the oil phase, and then isothermally mixing the two phases to obtain a homogeneous emulsified system comprises:
placing unstable components under alkaline conditions into the oil phase, respectively heating the second water phase and the oil phase, and then carrying out isothermal mixing on the two phases to obtain a uniform emulsification system;
or respectively heating the second water phase and the oil phase, isothermally mixing the two phases, and adding the unstable components under the alkaline condition into the mixed system to obtain a uniform emulsified system.
In one embodiment, the under alkaline conditions labile ingredient comprises at least one of an inorganic acid ester, a fatty acid ester, an aromatic chain hydrocarbon acid ester, a heterocyclic carboxylic acid ester, a lactone, etomidate, methyl salicylate, beclomethasone propionate, aspirin, artemisinin, erythromycin, dexamethasone acetate, procaine, tetracaine, atropine, pilocarpine, succinylcholine chloride, clofibrate, simvastatin, reserpine, rifampin, vitamin a acetate, vitamin C, spironolactone, midecamycin, isoamyl nitrite, glycerol nitrate, isosorbide dinitrate, nipagin ester.
In one embodiment, in the step of heating the second water phase and the oil phase respectively and then mixing the two phases isothermally to obtain a uniform emulsified system, the heating temperature of the second water phase is 75-90 ℃;
and/or the temperature of the emulsification process of mixing the two phases is 75-85 ℃;
and/or the temperature difference is within 10 ℃ when the two phases are mixed isothermally.
The preparation method of the emulsifiable paste under the alkaline condition firstly comprises the steps of11～C18The fatty acid and the alkaline substance are simultaneously placed in the water phase, the unstable component is not placed in the water phase under the alkaline condition, the direct contact between the unstable component and the alkaline substance under the alkaline condition is effectively avoided, the stability of the unstable component and the stability of an emulsification system under the alkaline condition (the pH value is more than 8.5) are effectively ensured, the prepared emulsifiable paste is also stable, and the preparation method has important significance for enhancing the using effect and the stability of the medicine.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The embodiment of the invention provides a preparation method of cream under alkaline condition, which comprises the following steps:
step S10: placing fatty acid and alkaline substance into the first water phase to obtain a second water phase, wherein the fatty acid comprises C11～C18At least one of a series of fatty acids;
step S20: respectively heating the second water phase and the oil phase, and then carrying out isothermal mixing on the two phases to obtain a uniform emulsification system;
step S30: and under the condition of stirring, cooling and solidifying the emulsifying system to obtain the cream.
Further, step S10 includes:
s101: mixing a first aqueous phase and an alkaline substance to completely dissolve the alkaline substance;
s102: and adding fatty acid into the first water phase, and stirring and heating to form uniform emulsion so as to obtain a second water phase.
In steps S101 and S102, due to C11～C18The fatty acids are lipophilic and insoluble or immiscible in water, C11～C18The fatty acid and the alkaline substance are mixed too fast, the gelling phenomenon is easy to generate, and the fatty acid and the alkaline substance are not easy to disperse, so the saponification is difficult, and multiple tests prove that the water-soluble component is dissolved firstly, and then the C is added11～C18Fatty acid, then during heating and stirring, with addition of C11～C18Gradually dissolving fatty acid, gradually reacting to obtain water phase, mixing uniformly, and mixing C11～C18The probability of gelling of fatty acids and alkaline materials too quickly is about 30%.
In step S102, the heating temperature is 70-99 deg.C, such as 70 deg.C, 71 deg.C, 72 deg.C, 73 deg.C, 74 deg.C, 75 deg.C, 76 deg.C, 77 deg.C, 78 deg.C, 79 deg.C, 89 deg.C, 99 deg.C, etc., and the experimental data shows that C11～C18The solubility of the fatty acid salt in water increases with increasing temperature, and the increased solubility helps to improve the uniformity of mixing of the materials in the aqueous phaseThereby improving the stability of the cream.
The first aqueous phase comprises at least one of glycerin, sodium carboxymethylcellulose, polyethylene glycol, sodium hydroxide, potassium hydroxide, calcium hydroxide, peregal, polysorbate, sodium lauryl sulfate, and water.
The fatty acid comprises at least one of lauric acid, myristic acid, palmitic acid, stearic acid and oleic acid, the alkali substance comprises at least one of sodium hydroxide, potassium hydroxide and calcium hydroxide, different fatty acid salt emulsifiers have different hydrophilic-hydrophobic balance values (HLB values) and different emulsification effects, for example, the HLB value of calcium stearate is about 3, the HLB value of sodium stearate is about 18, the HLB value of potassium stearate is about 7, and the HLB value of potassium oleate is about 20, and in order to stabilize an emulsification system, several emulsifiers are often required to be simultaneously applied to adjust the overall hydrophilic-hydrophobic balance values.
Further, step S20 includes:
placing unstable components under alkaline conditions into the oil phase, respectively heating the second water phase and the oil phase, and then carrying out isothermal mixing on the two phases to obtain a uniform emulsification system;
or respectively heating the second water phase and the oil phase, isothermally mixing the two phases, and adding the unstable components under the alkaline condition into the mixed system to obtain a uniform emulsified system.
Firstly, C is11～C18The fatty acid and the alkaline substance are simultaneously placed in the water phase, the unstable component is not placed in the water phase under the alkaline condition, the unstable component is effectively prevented from directly contacting with the alkaline substance under the alkaline condition, the fatty acid salt is generated in the subsequent stirring and heating process, the alkaline substance is consumed, the pH value of the system is enabled to be neutral or alkalescent (the pH value is less than or equal to 8.5), and the stability of the unstable component under the alkaline condition (the pH value is more than 8.5) is effectively ensured.
The unstable component under alkaline condition comprises at least one of inorganic acid ester, fatty acid ester, aromatic chain hydrocarbon acid ester, heterocyclic carboxylic ester, lactone, etomidate, methyl salicylate, beclomethasone propionate, aspirin, artemisinin, erythromycin, dexamethasone acetate, procaine, tetracaine, atropine, pilocarpine, succinylcholine chloride, clofibrate, simvastatin, reserpine, rifampicin, vitamin A acetate, vitamin C, spironolactone, midecamycin, isoamyl nitrite, nitroglycerin, isosorbide dinitrate and nipagin ester.
The second aqueous phase is heated at a temperature of 75-90 deg.C, such as 75 deg.C, 76 deg.C, 77 deg.C, 78 deg.C, 79 deg.C, 80 deg.C, 82 deg.C, 83 deg.C, 84 deg.C, 85 deg.C, 90 deg.C, etc., and is preferably used to prepare a cream, and the most commonly used oil-in-water emulsifiers, potassium stearate and sodium stearate, are preferably dispersed in water at 80-85 deg.C to form a uniform and semitransparent emulsion.
The temperature of the emulsification process of mixing the two phases is 75-85 ℃, for example, 75 ℃, 76 ℃, 77 ℃, 78 ℃, 79 ℃, 80 ℃, 82 ℃, 83 ℃, 84 ℃, 85 ℃ and the like, and the emulsification process is less than 75 ℃, and some solid greasy substances with higher melting points in the oil phase are easy to separate out.
The temperature difference of the two phases in isothermal mixing is within 10 ℃, for example, the temperature difference can be 0 ℃, 1 ℃, 2 ℃, 3 ℃, 4 ℃, 5 ℃, 6 ℃, 7 ℃, 8 ℃, 9 ℃, 10 ℃ and the like, the preferred temperature difference is within 5 ℃, the temperature difference of the two phases is small, so that the two phases are more beneficial to uniform mixing, experiments show that the temperature difference is within 10 ℃, the cream can be prepared, but the forming effect is poor, and the cream prepared by the temperature difference within 5 ℃ is better formed.
Further, in step S30, different types of creams are prepared, and the cooling and solidification temperatures of the emulsification system will also be different.
The preparation method of the emulsifiable paste under the alkaline condition firstly comprises the steps of11～C18The fatty acid and the alkaline substance are simultaneously placed in the water phase, the unstable component is not placed in the water phase under the alkaline condition, the direct contact between the unstable component and the alkaline substance under the alkaline condition is effectively avoided, the stability of the unstable component and the stability of an emulsification system under the alkaline condition (the pH value is more than 8.5) are effectively ensured, the prepared emulsifiable paste is also stable, and the preparation method has important significance for enhancing the using effect and the stability of the medicine.
The invention is described in further detail with reference to a part of the test results, which are described in detail below with reference to specific examples.
Example 1
Step S401: putting 0.06g of ethylparaben, 8g of white vaseline, 3g of lanolin, 3g of liquid paraffin, 2.5g of borneol, 10g of vegetable oil and 4g of artemisinin powder into a reaction container, heating to 75-80 ℃, and stirring uniformly after melting to obtain an oil phase;
step S402: putting 6g of glycerol, 0.3g of sodium hydroxide, 0.2g of potassium hydroxide and 54.94g of water into a reaction container, stirring to dissolve the glycerol, adding 8g of stearic acid, and heating to 80-85 ℃ under the stirring condition to obtain a water phase;
step S403: slowly adding the water phase obtained in the step S102 into the oil phase obtained in the step S101, continuously stirring at the rotation speed of 500rpm until emulsification is complete, and then condensing and subpackaging to obtain the artemisinin cream.
And (4) experimental conclusion: the artemisinin emulsifiable paste prepared by the method is stable in forming, stable in active ingredient artemisinin, free of amine pungent smell, simple in production operation, and free of degradation of the preservative ethylparaben in the preparation process.
Example 2
Step S501: taking 0.1g of methyl paraben, 0.1g of propyl paraben, 4g of white vaseline, 8g of cetostearyl alcohol and 2.5g of monoglyceride into a reaction vessel, heating to 75-80 ℃, and stirring uniformly after melting;
dissolving 0.01g beclomethasone dipropionate in 0.1g dimethyl sulfoxide, adding into the reaction container, and uniformly stirring to obtain an oil phase;
step S502: putting 6g of glycerol, 0.2g of sodium hydroxide, 0.3g of potassium hydroxide and 72.69g of water in a reaction container, stirring to dissolve the glycerol, adding 6g of stearic acid, and heating to 80-85 ℃ under the stirring condition to obtain a water phase;
step S503: and (3) slowly adding the water phase obtained in the step (S102) into the oil phase obtained in the step (S101), continuously stirring until the emulsification is complete under the condition that the rotation speed is 1000rpm, and then condensing and subpackaging to obtain the beclometasone dipropionate emulsifiable paste.
Two processes were compared: the results of measuring the content of unstable components (beclomethasone dipropionate, methyl paraben and propyl paraben) in the cream prepared by the formula process (placing stearic acid in a water phase) and the cream prepared by placing stearic acid in an oil phase respectively under the alkaline condition are shown in table 1.
Figure BDA0002304828490000091
TABLE 1
And (4) experimental conclusion: the beclomethasone dipropionate cream prepared by the method has stable forming, stable active ingredient beclomethasone dipropionate, no amine pungent smell and simple production operation, and the preservatives methyl hydroxybenzoate and propyl hydroxybenzoate are not degraded in the preparation process.
Example 3
Step S601: 3g of methyl salicylate, 0.05g of ethylparaben, 8g of white vaseline, 2g of lanolin, 2g of beeswax and 2.5g of menthol are taken to be placed in a reaction vessel, heated to 82-85 ℃, and stirred uniformly to obtain an oil phase after being melted;
step S602: putting 6g of glycerol, 0.1g of sodium hydroxide, 0.05g of potassium hydroxide and 68.3g of water into a reaction container, stirring to dissolve the glycerol, adding 6g of stearic acid and 2g of oleic acid, and heating to 80-82 ℃ under the stirring condition to obtain a water phase;
step S603: slowly adding the oil phase obtained in the step S301 into the water phase obtained in the step S302, continuously stirring until the emulsification is complete under the condition that the rotation speed is 500rpm, and then condensing and subpackaging to obtain the methyl salicylate cream.
Two processes were compared: the results of measuring the content of unstable components (methyl salicylate and ethylparaben) in the cream prepared according to the above formula process (stearic acid and oleic acid in water phase) and the content of unstable components (methyl salicylate and ethylparaben) in the cream prepared according to the formula process and the stearic acid and oleic acid in oil phase process are shown in table 2.
Figure BDA0002304828490000101
TABLE 2
And (4) experimental conclusion: the methyl salicylate emulsifiable paste prepared by the method has the advantages of stable forming, stable active ingredient methyl salicylate, no amine pungent smell, simple production operation and no degradation of the preservative ethylparaben in the preparation process.
Example 4
Step S701: taking 0.3g of spironolactone, 1g of clindamycin hydrochloride, 1g of azone, 1g of sorbitol monostearate, 8g of cetyl alcohol, 6g of liquid paraffin, 12g of propylene glycol, 0.5g of methyl paraben and 0.2g of propyl paraben in a reaction vessel, heating to 80 ℃, and stirring uniformly to obtain an oil phase after melting;
step S702: putting 4g of glycerol, 801.5 g of polysorbate, 0.1g of sodium hydroxide, 0.1g of potassium hydroxide and 57.3g of water into a reaction vessel, stirring to dissolve the glycerol, adding 7g of stearic acid, and heating to 80 ℃ under the stirring condition to obtain a water phase;
step S703: slowly adding the oil phase obtained in the step S401 into the water phase obtained in the step S402, continuously stirring until the emulsification is complete under the condition that the rotation speed is 800rpm, and then condensing and subpackaging to obtain the compound spironolactone cream.
And (4) experimental conclusion: the compound spironolactone cream prepared by the method is stable in forming, the active ingredients spironolactone, clindamycin hydrochloride and azone are stable, the amine pungent smell is avoided, the production operation is simple, and the preservatives methyl paraben and propyl paraben are not degraded in the preparation process.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.

Claims (10)

1. A method for preparing a cream under alkaline conditions, the method comprising:
placing fatty acid and alkaline substance into the first water phase to obtain a second water phase, wherein the fatty acid comprises C11～C18At least one of a series of fatty acids;
respectively heating the second water phase and the oil phase, and then carrying out isothermal mixing on the two phases to obtain a uniform emulsification system;
and under the condition of stirring, cooling and solidifying the emulsifying system to obtain the cream.
2. The method of making a cream under alkaline conditions of claim 1, wherein said step of placing the fatty acid and the alkaline material in a first aqueous phase to obtain a second aqueous phase comprises:
mixing a first aqueous phase and an alkaline substance to completely dissolve the alkaline substance;
and adding fatty acid into the first water phase, and stirring and heating to form uniform emulsion so as to obtain a second water phase.
3. The method for preparing a cream under alkaline conditions as claimed in claim 2, wherein the step of adding fatty acid to the first aqueous phase and heating while stirring to form a uniform emulsion, and the step of obtaining the second aqueous phase, the heating temperature is 70-99 ℃.
4. The method of claim 1, wherein the first aqueous phase comprises at least one of glycerin, sodium carboxymethylcellulose, polyethylene glycol, sodium hydroxide, potassium hydroxide, calcium hydroxide, peregal, polysorbate, sodium lauryl sulfate, and water.
5. The method of making a cream under alkaline conditions of claim 1 wherein the fatty acid comprises at least one of lauric acid, myristic acid, palmitic acid, stearic acid and oleic acid.
6. The method of claim 1, wherein the alkaline substance comprises at least one of sodium hydroxide, potassium hydroxide, and calcium hydroxide.
7. The method of claim 1, wherein the oil phase comprises at least one of cetyl alcohol, stearyl alcohol, cetostearyl alcohol, glycerin, liquid paraffin, petrolatum, monoglycerides, silicone oil, beeswax, and lanolin.
8. The method of preparing a cream under alkaline conditions according to claim 1, wherein said step of heating said second aqueous phase and said oil phase separately and then isothermally mixing the two phases to obtain a homogeneous emulsified system comprises:
placing unstable components under alkaline conditions into the oil phase, respectively heating the second water phase and the oil phase, and then carrying out isothermal mixing on the two phases to obtain a uniform emulsification system;
or respectively heating the second water phase and the oil phase, isothermally mixing the two phases, and adding the unstable components under the alkaline condition into the mixed system to obtain a uniform emulsified system.
9. The method of claim 8, wherein the under alkaline condition labile ingredient comprises at least one of an inorganic acid ester, a fatty acid ester, an aromatic chain acid ester, a heterocyclic carboxylic acid ester, a lactone, etomidate, methyl salicylate, beclomethasone propionate, aspirin, artemisinin, erythromycin, dexamethasone acetate, procaine, tetracaine, atropine, pilocarpine, succinylcholine chloride, clofibrate, simvastatin, reserpine, rifampin, vitamin a acetate, vitamin C, spironolactone, midecamycin, isoamyl nitrite, nitroglycerin, isosorbide dinitrate, and nipagin ester.
10. The method for preparing the cream under the alkaline condition as claimed in claim 1, wherein in the step of heating the second water phase and the oil phase respectively and then mixing the two phases isothermally to obtain a uniform emulsified system, the heating temperature of the second water phase is 75-90 ℃;
and/or the temperature of the emulsification process of mixing the two phases is 75-85 ℃;
and/or the temperature difference is within 10 ℃ when the two phases are mixed isothermally.
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Application publication date: 20200417