CN110693947A

CN110693947A - Gel preparation for treating skin diseases and preparation method thereof

Info

Publication number: CN110693947A
Application number: CN201911047131.4A
Authority: CN
Inventors: 张瀚文
Original assignee: Individual
Current assignee: Individual
Priority date: 2019-10-30
Filing date: 2019-10-30
Publication date: 2020-01-17

Abstract

The invention provides a gel preparation for treating skin diseases and a preparation method thereof, wherein the gel preparation comprises the following components in percentage by mass, namely 1-30% of distillate oil; 1-5% of eucalyptus oil; 1-5% of borneol; 0.1-2% of preservative; glycyrrhetinic acid 0.1-5%; 1-10% of ethanol; 1-5% of emulsifier A; 1-10% of polyol; 20-60% of deionized water; poloxamer 1881-20%; 1-5% of phospholipid; the sum of the mass fractions of the components is 100%, and poloxamer 188 is not included in the emulsifier A. The gel preparation contains the effective components such as glycyrrhetinic acid, distillate oil and the like, and various effective components with poor solubility are prepared into an oil-in-water system which has strong usability and small stimulation and is easy to clean, and the gel preparation is used for treating skin immune or inflammatory diseases such as eczema, dermatitis, psoriasis and the like.

Description

Gel preparation for treating skin diseases and preparation method thereof

Technical Field

The invention belongs to the technical field of gel preparations for treating skin diseases, and particularly relates to a gel preparation for treating skin diseases and a preparation method thereof.

Background

Eczema is the most common disease in dermatology, and various types of eczema can account for 20% of outpatients of dermatology, is a chronic recurrent disease and can last for months, years and even decades. The most significant symptom is severe pruritus, which can obviously affect the study, work and life of patients. Other conditions include papules, blisters, erosive surface formation, crusting and scaling, and also secondary infections, inflammation and the like. The etiology and pathogenesis of eczema are complex, and no clear conclusion is made at present, and the eczema is usually the result of the interaction of internal and external factors. Internal factors such as chronic digestive system diseases, mental stress, insomnia, overfatigue, mood changes, endocrine dyscrasia, infection, metabolism disorder and the like, and external factors such as living environment, climate changes, food and the like can influence the occurrence of eczema. External stimuli such as sunlight, cold, dryness, heat, hot water scalding, and various animal skins, plants, cosmetics, soaps, artificial fibers, etc. can be induced. Is a delayed type allergic reaction caused by complex internal and external factors. According to research, the prevalence rate of eczema in western countries reaches more than 10%, and the prevalence rate of eczema in Chinese population gradually approaches the value. With the gradual improvement of the living standard of Chinese people in recent years, the number of infectious skin diseases is gradually reduced, the number of allergic skin diseases is gradually increased, and the incidence rate of eczema is also shown to be increased by the result of epidemiological investigation.

In terms of treatment, the externally applied medicine containing the corticoids has the most obvious effect and is also a main medicine for treating eczema, but the externally applied medicine is easy to suffer from dependent dermatitis after long-term use.

Disclosure of Invention

In view of the above, the present invention aims to provide a gel preparation for treating skin diseases and a preparation method thereof, so as to overcome the defects of the prior art, the gel preparation of the present invention contains the effective components such as glycyrrhetinic acid and distilled oil, and various effective components with poor solubility are prepared into an oil-in-water system which has strong usability and small irritation and is easy to clean, and the gel preparation is used for skin immune or inflammatory diseases such as eczema, dermatitis, psoriasis, and the like.

In order to achieve the purpose, the technical scheme of the invention is realized as follows:

a gel preparation for treating skin diseases comprises the following components, by mass, 1-30% of distillate oil; 1-5% of eucalyptus oil; 1-5% of borneol; 0.1-2% of preservative; glycyrrhetinic acid 0.1-5%; 1-10% of ethanol; emulsifier A1-5%; 4-15% of polyhydric alcohol; 20-60% of deionized water; poloxamer 1881-20%; 1-5% of phospholipid; the sum of the mass fractions of the components is 100%, and poloxamer 188 is not included in the emulsifier A.

Preferably, the oil-distilling agent comprises the following components in percentage by mass, 5-20% of distillate oil; 1-5% of eucalyptus oil; 1-5% of borneol; 0.1-2% of preservative; glycyrrhetinic acid 0.1-5%; 1-10% of ethanol; emulsifier A1-5%; 4-15% of polyhydric alcohol; 20-60% of deionized water; poloxamer 18810-18%; 1-5% of phospholipid; the sum of the mass fractions of the components is 100%, and poloxamer 188 is not included in the emulsifier A.

Preferably, the distillate oil is one or more of black soybean distillate oil, pine distillate oil, bran distillate oil, coal tar, and egg oil, preferably black soybean distillate oil.

Preferably, the preservative can be one or more of sodium benzoate, potassium sorbate, phenoxyethanol, nipagin ester, cason, benzyl alcohol, phenethyl alcohol and salicylic acid, preferably phenoxyethanol;

preferably, the emulsifier is one or more of tween (sorbitan monolaurate) 20, tween 21, tween 40, tween 60, tween 61, tween 65, tween 80, tween 81, tween 85, sorbitan stearate 165, ceteareth PEG20, span (sorbitan monostearate) 20, span 60, span 80 and castor oil polyoxyethylene (10/25/40/60/80/90), and preferably tween 80, span 80 and castor oil polyoxyethylene.

Preferably, the polyhydric alcohol is one or more of ethanol, glycerol, propylene glycol, butylene glycol and 1, 2-pentanediol, and preferably glycerol.

The ethanol is chemically pure ethanol, analytically pure ethanol, dealdehydized ethanol or denatured ethanol, preferably analytically pure ethanol.

Preferably, the phospholipid is natural phospholipid and/or synthetic phospholipid, preferably, the phospholipid comprises one or more of phosphatidylcholine such as egg yolk lecithin, soybean lecithin, hydrogenated soybean lecithin, distearoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, dimyristoyl phosphatidylcholine and the like, and preferably, the phospholipid is egg yolk lecithin and hydrogenated soybean lecithin.

The present invention also provides a method for preparing the gel formulation for treating skin diseases as described above, comprising the steps of,

1) mixing the emulsifier A, the polyhydric alcohol, the deionized water and the poloxamer 188, heating to 60-80 ℃, stirring at 600r/min for 100-;

2) cooling the solution in the step 1) to 40-60 ℃, adding phospholipid, stirring at 600r/min for 100-; then placing the mixture to room temperature to obtain a water phase;

3) mixing glycyrrhetinic acid and ethanol, heating for dissolving, cooling, and obtaining a low-temperature phase 2;

4) mixing the distillate oil, eucalyptus oil, borneol and preservative with the low-temperature phase 2 prepared in the step 3), and slowly stirring until the mixture is uniformly mixed and smooth to form a mixed low-temperature phase;

5) and (3) injecting the mixed low-temperature phase prepared in the step 4) into the water phase in the step 2) in a trickle manner, rapidly stirring by using a stirring paddle while injecting the mixed low-temperature phase until the mixed low-temperature phase is completely mixed, and continuously stirring for more than 30 minutes to ensure that the mixed low-temperature phase is uniformly mixed.

The gel preparation for treating the skin diseases is applied to medicines or skin care products for treating the skin diseases and preparation thereof.

The gel preparation prepared by the preparation method is applied to medicines or skin care products for treating skin diseases and preparation thereof.

Glycyrrhetinic acid (also called glycyrrhetinic acid) is an effective component of Glycyrrhrizae radix, and has antiinflammatory and immunoregulatory effects. Its anti-inflammatory and anti-allergic response may be associated with inhibition of capillary permeability, antihistamine or reduced cellular responsiveness to stimuli. Is clinically used for treating various inflammations. Black soybean distillate oil, bran distillate oil, coal tar, egg yolk oil, pine oil, etc. are traditional Chinese medicine preparations for relieving itching, diminishing inflammation, astringing and resisting bacteria, and are often used for skin diseases such as acute and chronic eczema, neurodermatitis, psoriasis, infantile eczema, etc. The mechanism of action of black soybean distillate oil has been studied by Japanese scientists, and the anti-inflammatory action is mainly due to the inhibition of vascular hyperpermeability and acute edema in the early stage of inflammatory reaction by the action of antihistamine and bradykinin.

For example, black soybean oil can significantly inhibit the movement of neutrophils and macrophages. In addition, the Minimum Inhibitory Concentration (MIC) of the black soya bean distillate oil to bacteria is 156.3-2500 ug/ml, the minimum bactericidal concentration (MCC) is 156.3-5000 ug/ml, the MIC and the MCC are both 156.3ug/ml for the trichophyton, the lower numerical value is shown, and the black soya bean distillate oil is judged to have stronger antibacterial power to the trichophyton.

The glycyrrhetinic acid is compounded with various types of distillate oil or tar, and has the effects of resisting inflammation, regulating immunity, resisting bacteria, relieving itching and the like, so that the effect of treating eczema and psoriasis is achieved.

However, glycyrrhetinic acid is insoluble in water and oil, and soluble in hot ethanol; the black soya bean distillate oil and the like are insoluble in water, soluble in ethanol, sticky, have strong special odor, are easy to be stained with clothes, are difficult to be removed by using a common detergent, and are very inconvenient to use. The invention improves the dissolution properties of the two main active ingredients and also leads the two main active ingredients to be more convenient to form compatibility.

Compared with the prior art, the gel preparation for treating skin diseases and the preparation method thereof have the following advantages:

the invention relates to a compound gel preparation which takes the active ingredients of glycyrrhetinic acid and distilled oil as main active ingredients, and the invention improves the properties and the use simplicity of the glycyrrhetinic acid and the distilled oil by providing a safe and effective preparation formula and a process flow so as to achieve the effect of effectively relieving, controlling and treating skin chronic diseases such as eczema, dermatitis, psoriasis and the like.

The gel ointment is verified by efficacy, the using population comprises various eczema and psoriasis patients, and the using parts comprise, but are not limited to, neck, wrist, ankle, arm, palm, sole and the like. The results of the verification show that 80% of patients are relieved, improved and healed to different degrees. The average time of onset is 7 days, and the average time of recovery is 14 days;

the chemical structure of glycyrrhetinic acid is similar to that of steroid hormone, and can raise the activity of endogenous and exogenous glucocorticoid. And the glucocorticoid receptor agonistic activity of the glycyrrhetinic acid is far lower than that of glucocorticoid, so that dependence cannot be formed. Although the distilled oil component lacks clear pharmacological action and molecular mechanism research, the distilled oil component has been used as a medicament for various skin diseases for a long time, has sufficient verification on curative effect, but is limited by the problems of oily touch, special odor, difficult treatment after being stained with clothes and the like, so that the compliance of patients is reduced. By the invention, all tested persons show that the product has appropriate smell, good spreadability, is not easy to be stained with clothes and is easy to clean. The endogenous hormone regulation effect of the glycyrrhetinic acid is cooperated with the local immunity regulation and broad-spectrum antibacterial effect of the distillate oil components, so as to achieve the ideal curative effect on skin diseases such as eczema, psoriasis and the like.

Drawings

FIG. 1 is a diagram of a gel paste of example III;

FIG. 2 is a gel of example III observed under a microscope;

FIGS. 3 and 4 are diagrams illustrating the effects of the third embodiment;

Detailed Description

Unless defined otherwise, technical terms used in the following examples have the same meanings as commonly understood by one of ordinary skill in the art to which the present invention belongs. The test reagents used in the following examples, unless otherwise specified, are all conventional biochemical reagents; the experimental methods are conventional methods unless otherwise specified.

The present invention will be described in detail with reference to examples.

The first embodiment is as follows:

mixing span 601 g, Tween 600.5 g, glycerol 10g, deionized water 47.5g, and poloxamer-18810 g, heating to 60 deg.C, mixing, continuously magnetically stirring for 30 min, cooling to 40 deg.C, adding egg yolk lecithin 1g, magnetically stirring, mixing, and cooling to room temperature to obtain water phase. Heating and stirring 2g of glycyrrhetinic acid, dissolving in 10g of ethanol until the glycyrrhetinic acid is completely dissolved, and cooling to room temperature to prevent precipitation for later use. Mixing bran distillate oil 10g, oleum Eucalypti 5g, Borneolum 2g, and methyl hydroxybenzoate 1g with the above Glycyrrhetinic acid ethanol solution, and slowly stirring to mix well and smooth to form mixed low temperature phase. And injecting the mixed low-temperature phase into the water phase in a trickle manner, rapidly stirring by using a stirring paddle while injecting the mixed low-temperature phase until the mixed low-temperature phase is completely mixed, and continuously stirring for more than 30 minutes to ensure that the mixed low-temperature phase is uniformly mixed. And then can be packed into an aluminum tube for standby.

Example two:

uniformly mixing 801 g of tween, 10g of glycerol, 5g of butanediol, 41g of deionized water and-18815 g of poloxamer, heating to 80 ℃, mixing, continuously magnetically stirring for 30 minutes, cooling to 50 ℃, adding 3g of hydrogenated soybean phospholipid, magnetically stirring, uniformly mixing, and cooling to room temperature for later use, wherein the mixture is an aqueous phase. Heating and stirring 2g of glycyrrhetinic acid, dissolving in 8g of ethanol until the glycyrrhetinic acid is completely dissolved, and cooling to room temperature to prevent precipitation for later use. Mixing 10g of pine tar oil, 2g of eucalyptus oil, 2g of borneol and 1g of benzyl alcohol with the ethanol solution of glycyrrhetinic acid, and slowly stirring until the mixture is uniformly mixed and smooth to form a mixed low-temperature phase. And injecting the mixed low-temperature phase into the water phase in a trickle manner, rapidly stirring by using a stirring paddle while injecting the mixed low-temperature phase until the mixed low-temperature phase is completely mixed, and continuously stirring for more than 30 minutes to ensure that the mixed low-temperature phase is uniformly mixed. And then can be packed into an aluminum tube for standby.

Example three:

uniformly mixing 802 g of tween, 10g of glycerol, 52.5g of deionized water and 18815 g of poloxamer, heating to 75 ℃, mixing, continuously magnetically stirring for 30 minutes, cooling to 60 ℃, adding 1.5g of egg yolk lecithin, magnetically stirring, uniformly mixing, and cooling to room temperature for later use, wherein the mixture is an aqueous phase. Heating and stirring 0.5g glycyrrhetinic acid, dissolving in 5g ethanol until completely dissolving, and cooling to room temperature to precipitate. Mixing semen Sojae Atricolor distillate oil 10g, oleum Eucalypti 2g, Borneolum 1g, and phenoxyethanol 0.5g with the ethanol solution of Glycyrrhetinic acid, and slowly stirring to mix well and smooth to form mixed low temperature phase. And injecting the mixed low-temperature phase into the water phase in a trickle manner, rapidly stirring by using a stirring paddle while injecting the mixed low-temperature phase until the mixed low-temperature phase is completely mixed, and continuously stirring for more than 30 minutes to ensure that the mixed low-temperature phase is uniformly mixed. And then can be packed into an aluminum tube for standby.

Example four:

uniformly mixing castor oil polyoxyethylene-404 g, glycerol 10g, butanediol 2g, deionized water 50g and poloxamer-1886.5 g, heating to 65 ℃ for mixing, cooling to 50 ℃ after 10 minutes of high-pressure average value, adding distearyl phosphatidyl choline 3.5g, uniformly mixing, and cooling to room temperature for later use, wherein the mixture is a water phase. 0.8g of glycyrrhetinic acid is taken, heated, stirred and dissolved in 5g of ethanol until the glycyrrhetinic acid is completely dissolved, and the glycyrrhetinic acid is cooled to room temperature and is not separated out for standby. Mixing coal tar 10g, eucalyptus oil 2g, Borneolum Syntheticum 2g, and cason 1g with the ethanol solution of glycyrrhetinic acid, and slowly stirring to mix and smooth to form mixed low temperature phase. And injecting the mixed low-temperature phase into the water phase in a trickle manner, rapidly stirring by using a stirring paddle while injecting the mixed low-temperature phase until the mixed low-temperature phase is completely mixed, and keeping the high-pressure average value for more than 10 minutes to ensure that the mixed low-temperature phase is uniformly mixed. And then can be packed into an aluminum tube for standby.

The products obtained in the first to fourth examples were tested separately.

1. Macroscopically observing the finished product, wherein the initial state of the synthesis, the stable state after being heated and placed for 6 hours at 60 ℃, the stable state of the product after being placed for half a year at room temperature and 4 ℃ and the absorption state of the product on the skin are observed, and the results are shown in the following table 1.

TABLE 1

2. And (5) microscopic observation of a finished product.

The finished product is an oil-in-water system, specifically, a water phase gel system wraps the components in the low-temperature oil phase component, and the low-temperature oil phase component is uniformly and stably dispersed in the water phase by small oil drops smaller than 50 microns, so that a macroscopically stable and water-soluble gel finished product system is formed. The product of example three was thinly coated on a glass slide and observed by a 400X optical microscope, and the result is shown in FIG. 2. The products of the remaining examples were also oil-in-water systems, with the oil phase components being uniformly dispersed in the water phase as small oil droplets of less than 50 microns.

3. Verification of usage effects

Taking the third embodiment as an example, the skin care product is used for the skin of patients with eczema and psoriasis.

The using method comprises the following steps:

twice a day in the morning and at night or three times in the morning, at night, cleaning the affected part, taking a proper amount of ointment, thinly applying the ointment to the affected part, massaging for several seconds in a circle until the ointment is semi-absorbed, and remaining the ointment on the affected part for continuous absorption. The application is continued for 2 weeks or until recovery.

Fig. 3 shows that the patient has neck eczema which is not cured for several months, and the patient can be cured for 2 weeks after the gel paste in the third embodiment is used.

In fig. 4, the patients with mild primary psoriasis at the back of ears and scalp in the third example can be cured after 5 days. The recovery means that the pathological changes of the skin at the affected part disappear, no molt, no redness, no pruritus and no relapse in a short time.

After 20 patients have undergone the above tests, it was verified that 80% of the patients had different degrees of remission, improvement and recovery. The average time of onset is 7 days, and the average time of recovery is 14 days;

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, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims

1. A gel formulation for treating a skin condition, comprising: comprises the following components in percentage by mass, distilled oil 1-30%; 1-5% of eucalyptus oil; 1-5% of borneol; 0.1-2% of preservative; glycyrrhetinic acid 0.1-5%; 1-10% of ethanol; emulsifier A1-5%; 4-15% of polyhydric alcohol; 20-60% of deionized water; poloxamer 1881-20%; 1-5% of phospholipid; the sum of the mass fractions of the components is 100%, and poloxamer 188 is not included in the emulsifier A.

2. The gel formulation for the treatment of skin disorders according to claim 1, wherein: comprises the following components with the mass fraction of 5-20 percent of distillate oil; 1-5% of eucalyptus oil; 1-5% of borneol; 0.1-2% of preservative; glycyrrhetinic acid 0.1-5%; 1-10% of ethanol; 1-5% of emulsifier A; 4-15% of polyhydric alcohol; 20-60% of deionized water; poloxamer 18810-18%; 1-5% of phospholipid; the sum of the mass fractions of the components is 100%, and poloxamer 188 is not included in the emulsifier A.

3. The gel formulation for the treatment of skin disorders according to claim 1, wherein: the distillate oil is one or more of black soybean distillate oil, pine distillate oil, bran distillate oil, coal tar, and egg oil, preferably black soybean distillate oil.

4. The gel formulation for the treatment of skin disorders according to claim 1, wherein: the antiseptic is one or more of sodium benzoate, potassium sorbate, phenoxyethanol, nipagin ester, cason, benzyl alcohol, phenethyl alcohol, and salicylic acid, preferably phenoxyethanol.

5. The gel formulation for the treatment of skin disorders according to claim 1, wherein: the emulsifier is one or more of tween (sorbitan monolaurate) 20, tween 21, tween 40, tween 60, tween 61, tween 65, tween 80, tween 81, tween 85, sorbitan stearate 165, ceteareth PEG20, span (sorbitan monostearate) 20, span 60, span 80 and castor oil polyoxyethylene (10/25/40/60/80/90), and the preferred emulsifier is tween 80, span 80 and castor oil polyoxyethylene.

6. The gel formulation for the treatment of skin disorders according to claim 1, wherein: the polyalcohol is one or more of ethanol, glycerol, propylene glycol, butanediol, and 1, 2-pentanediol, preferably glycerol.

7. The gel formulation for the treatment of skin disorders according to claim 1, wherein: the phospholipid is natural phospholipid and/or synthetic phospholipid, preferably, the phospholipid comprises one or more of phosphatidylcholine such as egg yolk lecithin, soybean lecithin, hydrogenated soybean lecithin, distearoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, dimyristoyl phosphatidylcholine, and the like, and preferably, the phospholipid is egg yolk lecithin and hydrogenated soybean lecithin.

8. A method of preparing a gel formulation for the treatment of a skin disorder according to any one of claims 1 to 7, wherein: comprises the following steps of (a) carrying out,

9. The use of the gel formulation according to any one of claims 1 to 7 for the treatment of skin diseases in the manufacture of a medicament or skin care product for the treatment of skin diseases.

10. The use of the gel preparation prepared by the preparation method according to claim 8 in the preparation of a medicament or skin care product for treating skin diseases and the preparation thereof.