阅读说明：本技术 一种聚桂醇尿素乳膏及其制作方法 (Polycinnamic alcohol urea emulsifiable paste and preparation method thereof ) 是由 王立兴 朱国理 王斌 乐云峰 林亚玲 于 2021-01-06 设计创作，主要内容包括：本发明提供一种聚桂醇尿素乳膏及其制作方法,乳膏由聚桂醇、尿素、卡波姆、甘油、苯甲醇、氨丁三醇、二甲硅油、苯基聚二甲基硅氧烷、液状石蜡、鲸蜡醇棕榈酸酯、硬脂酸、辛基十二醇、聚山梨酯80及纯化水组成。处方中辛基十二醇的用量为5％～15％(W/W),卡波姆用量为0.5％～1.5％(W/W),卡波姆加氨丁三醇的水相溶液一起溶胀的速度更快。本发明的有益效果是,卡波姆的溶胀速度及效果更好,节约生产时间与成本；辛基十二醇与卡波姆是影响本品疗效的关键性辅料,控制好其用量才能保证产品的临床疗效。(The invention provides a lauromacrogol urea emulsifiable paste and a preparation method thereof, wherein the emulsifiable paste consists of lauromacrogol, urea, carbomer, glycerol, benzyl alcohol, tromethamine, dimeticone, phenyl polydimethylsiloxane, liquid paraffin, cetyl palmitate, stearic acid, octyl dodecanol, polysorbate 80 and purified water. In the formula, the dosage of the octyldodecanol is 5-15% (W/W), the dosage of the carbomer is 0.5-1.5% (W/W), and the swelling speed of the carbomer and the aqueous phase solution of the tromethamine is higher. The invention has the advantages that the swelling speed and effect of carbomer are better, and the production time and cost are saved; octyl dodecanol and carbomer are key auxiliary materials influencing the curative effect of the product, and the clinical curative effect of the product can be ensured only by controlling the dosage of the octyl dodecanol and the carbomer.)

1. A lauromacrogol urea cream, wherein the formula (W/W) of the cream comprises 3% of lauromacrogol, 5% of urea, 1.7% of glycerol, 1.0% of benzyl alcohol, 1.2% of tromethamine, 2% of dimethicone, 5% of phenyl polydimethylsiloxane, 1.5% of liquid paraffin, 0.5% of cetyl palmitate, 1.5% of stearic acid, 803% of polysorbate and a proper amount of purified water; the method is characterized in that: the cream formula also comprises 5 to 15 percent of octyl dodecanol and 0.5 to 1.5 percent of carbomer; the sum of the weight percentages of the components of the cream formula is 100%.

2. The lauromacrogol urea cream as claimed in claim 1, wherein: the octyldodecanol is preferably used in an amount of 10% (W/W); the amount of carbomer is preferably 1.3% (W/W).

3. The method for preparing the lauromacrogol urea cream as claimed in claim 1 or 2, which is characterized in that: the swelling mode of the carbomer in the formula of the emulsifiable paste is that the carbomer and tromethamine are mixed and swelled by an aqueous phase solution; the cream is realized by the following steps:

step one: water phase components: taking urea, glycerol, benzyl alcohol, tromethamine and water, stirring and dissolving, and supplementing a proper amount of water according to the water evaporation amount in the operation process; adding carbomer, stirring, standing for swelling for 3 hr, stirring, and heating to 70 deg.C;

step two: oil phase components: heating lauromacrogol, dimethicone, phenyl dimethicone, liquid paraffin, cetyl palmitate, stearic acid, octyldodecanol, and polysorbate 80 to 70 deg.C for melting, and stirring;

step three: and (3) slowly adding the oil into the water phase at a constant speed with the rotation speed of 400 rpm under stirring, keeping the temperature of 70 ℃ for stirring for 30 minutes, stopping heating, continuously stirring, cooling to below 40 ℃, stopping stirring, and filling to obtain the water-based paint.

Technical Field

The invention relates to a lauromacrogol urea emulsifiable paste and a preparation method thereof.

Background

The lauromacrogol urea cream is used for treating pruritus, eczema, dermatitis, and ichthyosis caused by itching relieving and moisturizing. Can also be used for the continuous treatment and the subsequent treatment of the skin diseases. Each 1g of the cream contains 3.0% (W/W) of lauromacrogol and 5.0% (W/W) of urea. The product has definite effect and good safety, can be sold in places such as supermarkets, gas stations and the like as common medicines, and does not appear to be on the market at home.

Eczema, dermatitis and scaling are common diseases of the skin, and the most obvious symptom of the diseases is pruritus. The incidence rate of eczema is the highest and accounts for 20% of the outpatient amount of dermatology, wherein the incidence rate of infantile eczema accounts for more than 70%. Eczema can obviously affect the learning, working and living of patients, and serious patients can also affect sleeping.

The domestic external preparation for relieving itching caused by eczema or dermatitis symptoms is a traditional Chinese medicine preparation except hormone medicines, and the traditional Chinese medicine external preparation has the problems of smell, clothes dyeing and the like. The product does not contain hormone components, has no special and obvious smell and color, has unique market advantages and has great domestic market potential.

Urea is a physiological product of human protein metabolism, naturally exists in the skin, and can soften the stratum corneum, increase the hydration of the skin and keep moisture for 24 hours when being locally administered. The lauromacrogol is mainly used as a hardening agent clinically, and meanwhile, the lauromacrogol has a slight local anesthetic effect and a good itching relieving effect, and can not be absorbed and enter blood circulation when being externally used, so that the lauromacrogol has good tolerance and safety to a human body.

Chinese patent CN 108853312A discloses a lauromacrogol gel for external use and a preparation method thereof, and the components mainly comprise urea, lauromacrogol, aloe extract, benzalkonium chloride, sodium alginate, potassium sorbate, menthol, glycerol, disodium hydrogen phosphate dodecahydrate, sodium dihydrogen phosphate dihydrate and purified water. Can be used for treating burn and scald of 1-2 deg.C, mosquito bite, and abrasion, and has antipruritic, analgesic, antiinflammatory, and repercussive effects. The main components and the dosage, the auxiliary materials and the functions of the product in the patent are greatly different from those of the product.

Disclosure of Invention

The invention aims to provide a lauromacrogol urea emulsifiable paste and a preparation method thereof, which are a good prescription and a good process, ensure good in-vitro release degree of lauromacrogol and urea and good transdermal rate of urea, and ensure clinical curative effect.

The invention is realized in such a way that the formula (W/W) of the cream comprises 3% of lauromacrogol, 5% of urea, 1.7% of glycerol, 1.0% of benzyl alcohol, 1.2% of tromethamine, 2% of dimeticone, 5% of phenyl polydimethylsiloxane, 1.5% of liquid paraffin, 0.5% of cetyl palmitate, 1.5% of stearic acid, 803% of polysorbate and a proper amount of purified water; the cream formula also comprises 5 to 15 percent of octyl dodecanol and 0.5 to 1.5 percent of carbomer; the sum of the weight percentages of the components of the cream formula is 100%.

The octyldodecanol used in the present invention is preferably 10% (W/W); the amount of carbomer is preferably 1.3% (W/W).

According to the preparation method of the lauromacrogol urea emulsifiable paste, carbomer in the emulsifiable paste formula is swelled by mixing carbomer with tromethamine in an aqueous phase solution; the cream is realized by the following steps:

step one: water phase components: taking urea, glycerol, benzyl alcohol, tromethamine and water, stirring and dissolving, and supplementing a proper amount of water according to the water evaporation amount in the operation process; adding carbomer, stirring, standing for swelling for 3 hr, stirring, and heating to 70 deg.C;

step two: oil phase components: heating lauromacrogol, dimethicone, phenyl dimethicone, liquid paraffin, cetyl palmitate, stearic acid, octyldodecanol, and polysorbate 80 to 70 deg.C for melting, and stirring;

step three: and (3) slowly adding the oil into the water phase at a constant speed with the rotation speed of 400 rpm under stirring, keeping the temperature of 70 ℃ for stirring for 30 minutes, stopping heating, continuously stirring, cooling to below 40 ℃, stopping stirring, and filling to obtain the water-based paint.

The main technical key points 1 of the invention are as follows: the dosage of the prescription of the octyldodecanol is controlled, the component has obvious influence on the skin permeation rate of the urea, and can achieve good in vitro release rate and skin permeation rate within the range of 5-15 percent, thereby effectively ensuring the clinical curative effect. Preferably, the amount of octyldodecanol used in the formulation is 10%.

The main technical key points 2 of the invention are as follows: the dosage of the carbomer prescription is controlled, the component has obvious influence on the in vitro release rate of the lauromacrogol, and the good in vitro release rate can be achieved within the range of 0.5-1.5%, so that the clinical curative effect is effectively ensured. The preferred formulation has a carbomer level of 1.3%.

The main technical key points 3 of the invention are as follows: the tromethamine and the carbomer are swelled together in the water phase, the tromethamine is a pH value regulator, and the tromethamine is added in the early stage, so that the swelling speed of the carbomer is accelerated, the swelling of the carbomer is more uniform, the emulsifying uniformity of the emulsifiable paste is controlled, and the swelling time of the carbomer is shortened.

Drawings

FIG. 1 is a graph of the time-release rate of urea from a preparation of the invention (0.5%, 1.0%, 1.3%, 1.5% carbomer).

FIG. 2 is a graph of the time-release rate of lauromacrogol from a preparation of the present invention (0.5%, 1.0%, 1.3%, 1.5% carbomer).

FIG. 3 is a graph of time-transdermal rate of urea from a preparation of the present invention (5%, 10%, 15% octyldodecanol).

Detailed Description

The present invention will be described in detail with reference to the following examples and FIGS. 1 to 3.

The product contains lauromacrogol, urea, carbomer, glycerol, benzyl alcohol, tromethamine, dimethicone, phenyl polydimethylsiloxane, liquid paraffin, cetyl palmitate, stearic acid, octyldodecanol, polysorbate 80 and purified water.

The swelling pattern of carbomer was examined. The carbomer + water and the carbomer + tromethamine aqueous phase solutions are respectively swelled and stirred at the same interval, and the transparency of the gel is taken as an index, so that the swelling time of the carbomer + water is about 6 hours (more ideal for swelling for 12 hours), and the swelling time of the carbomer + tromethamine aqueous phase solution is about 3 hours, and the result shows that the swelling speed after alkalization is obviously higher than that of a single aqueous solution, and the transparency after swelling is good (no colloidal particle lumps).

The swelling method can effectively reduce production operation time, ensure uniformity of carbomer in the finished product, and avoid fine particle jelly after coating.

The in vitro release rate of the lauromacrogol and the urea is taken as an index, and the dosage of the auxiliary materials is screened through an orthogonal test, so that the dosage of the auxiliary materials in the prescription is preliminarily determined.

The preliminary prescription determined is as follows:

the most critical factor of the influence of the in vitro release rate of the carbomer is determined by screening the dosage of the prescription auxiliary materials, so that the single-factor investigation of the dosage of the carbomer is carried out according to the preliminarily determined dosage of the prescription auxiliary materials. Except carbomer, the dosages of other raw and auxiliary materials are unchanged, the dosages of carbomer are respectively adjusted to be 0.5%, 1.0%, 1.3% and 1.5%, and the in-vitro release rate of lauromacrogol and urea is taken as an index.

Example 1

Except that the amount of carbomer is 0.5%, the amount of the raw materials and auxiliary materials of the prescription is the same as that of the preliminarily determined prescription.

Example 2

The amount of carbomer is 1.0%, and the amount of the other raw materials and auxiliary materials in the prescription is the same as that in the preliminarily determined prescription.

Example 3

Except that the amount of carbomer is 1.3 percent, the amount of other raw and auxiliary materials of the prescription is the same as that of the preliminarily determined prescription.

Example 4

Except that the amount of carbomer is 1.5 percent, the amount of other raw and auxiliary materials of the prescription is the same as that of the preliminarily determined prescription.

The preparation process is the same as the preparation method of the lauromacrogol urea cream.

The in vitro release degree test is carried out on the examples 1-4 according to the guiding principle requirements of the external application, the in vitro release degree results of the urea and the lauromacrogol in the self-prepared product are shown in the following tables 1 and 2, and the in vitro release degree curves are shown in the attached figures 1 and 2.

The data in the tables 1 and 2 show that the dosage of carbomer has no obvious influence on the release rate of urea, but has obvious influence on the in vitro release rate of lauromacrogol, the dosage needs to be controlled within the range of 0.5-1.5%, and the release rate of lauromacrogol is relatively proper.

According to the preliminarily determined prescription, the dosage of the octyldodecanol in the prescription is considered. Except for the octyl dodecanol, the dosages of other raw materials and auxiliary materials are unchanged, the dosages of the octyl dodecanol are respectively adjusted to be 5 percent, 10 percent and 15 percent, and the transdermal rate of the urea on the skin of the rat is taken as an index.

Example 5

Except that the dosage of the octyldodecanol is 5 percent, the dosages of the raw materials and the auxiliary materials of the other prescriptions are the same as the preliminarily determined prescription.

Example 2

The dosage of the octyldodecanol is 10 percent, and the dosages of the raw materials and the auxiliary materials of the rest prescriptions are the same as the preliminarily determined prescription.

Example 6

Except that the dosage of the octyldodecanol is 15 percent, the dosages of the raw materials and the auxiliary materials of the other prescriptions are the same as the preliminarily determined prescription.

The preparation process is the same as the preparation method of the lauromacrogol urea cream.

The transdermal rate test of rat skin is carried out according to the requirement of the external application guiding principle in the examples 2, 5 and 6, and the transdermal rate of the urea is analyzed. The results are shown in Table 3 below, and the graph of the transdermal rate of rat skin is shown in FIG. 3.

The data in the table 3 show that the dosage of the octyl dodecanol has a significant influence on the transdermal rate of the urea, and the dosage needs to be controlled within the range of 5-15%, so that the transdermal rate of the urea of the self-prepared product can be effectively ensured.