CN114452257B - Selenium disulfide foam agent for skin care and preparation method thereof - Google Patents

Selenium disulfide foam agent for skin care and preparation method thereof Download PDF

Info

Publication number
CN114452257B
CN114452257B CN202210387189.9A CN202210387189A CN114452257B CN 114452257 B CN114452257 B CN 114452257B CN 202210387189 A CN202210387189 A CN 202210387189A CN 114452257 B CN114452257 B CN 114452257B
Authority
CN
China
Prior art keywords
foam
skin
selenium disulfide
selenium
antioxidant
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202210387189.9A
Other languages
Chinese (zh)
Other versions
CN114452257A (en
Inventor
不公告发明人
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Xinjiyuan Beijing Pharmaceutical Technology Co ltd
Original Assignee
Xinjiyuan Beijing Pharmaceutical Technology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Xinjiyuan Beijing Pharmaceutical Technology Co ltd filed Critical Xinjiyuan Beijing Pharmaceutical Technology Co ltd
Priority to CN202210387189.9A priority Critical patent/CN114452257B/en
Publication of CN114452257A publication Critical patent/CN114452257A/en
Application granted granted Critical
Publication of CN114452257B publication Critical patent/CN114452257B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/04Sulfur, selenium or tellurium; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183Amino acids, e.g. glycine, EDTA or aspartame
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/12Aerosols; Foams
    • A61K9/122Foams; Dry foams
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Dispersion Chemistry (AREA)
  • Dermatology (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

The invention relates to a selenium disulfide foam agent for skin care and a preparation method thereof, wherein the selenium disulfide foam agent comprises the following raw materials in percentage by mass: 0.5-3.0% of selenium disulfide micro powder, 12-20% of foaming agent, 2-5% of skin humectant, 1.5-3% of skin conditioner, 6-10% of foam propping agent, 1-2.5% of penetration enhancer, 0.5-2% of phosphatidylserine, 0.3-2% of amino acid, 0.03-0.1% of antioxidant, 5-8% of propellant and the balance of water. The selenium sulfide foaming agent provided by the invention has rich and fine foam, good sensory experience of users, low content of selenium sulfide and good safety, and can effectively prevent and treat skin symptoms caused by fungi and bacteria.

Description

Selenium disulfide foam agent for skin care and preparation method thereof
Technical Field
The invention relates to the technical field of medicines, in particular to a selenium disulfide foaming agent for skin care.
Background
The selenium disulfide has antibacterial, antifungal, and spore-killing effects on Trichophyton mentagrophytes, and can inhibit growth of epidermal cells of head. Therefore, the shampoo is widely used for nursing the scalp and the hair, and has good curative effects on removing dandruff and inhibiting scalp pruritus. For the first time, selenium sulphide has also been shown to be very effective in treating certain skin conditions of the stratum corneum, such as tinea versicolor.
At present, the selenium sulfide lotion is used as a medicine, is mostly used for washing hair and inhibiting scalp itch, and is less researched for specially aiming at the selenium sulfide lotion for skin care. If the dosage of the selenium disulfide is less, the treatment effect on tinea versicolor and other symptoms is poor. But the content of the selenium disulfide is increased, and certain safety risk exists. Selenium disulfide as a lotion mainly has the following defects at present: 1) based on the characteristic that selenium disulfide is almost insoluble in water or an organic solvent, the selenium disulfide lotion can be definitely a suspension, and is limited by a selenium disulfide production process in the market, the particle size of selenium disulfide powder is large, the particle size distribution is uneven, the instability of the selenium disulfide in the lotion suspension is influenced, and the lotion effect and the use experience are further influenced. The medicinal powder has poor dispersion uniformity and unstable suspension, and the medicinal powder at the local medicinal part is gathered to cause damage to the skin. 2) Because the selenium disulfide is easily oxidized and blackened, the risk of oxidative blackening exists in the selenium disulfide lotion in the storage process. Selenium disulfide can resist fungi, has beneficial physiological effects, still belongs to a toxic substance, has certain stimulation to eyes, skin and mucous membrane, and needs to reduce the dosage as far as possible, but the dosage of selenium disulfide lotion which can achieve the effects in the market at present is more, which is also the reason of less research on skin care products or medicines based on selenium disulfide.
In order to solve the problem that selenium disulfide is difficult to disperse in a medium, the prior art reports that the selenium disulfide is prepared into superfine powder with the particle size of 1-50 microns, so that the defects of easy agglomeration and sedimentation in a selenium disulfide suspending agent can be obviously improved. However, the particle size of selenium disulfide is too small, which has too strong skin penetration effect and is not beneficial for treatment. The main treatment mechanism of the selenium disulfide lotion is that the medicament passes through the horny layer and enters the epidermal layer to play a role in the epidermal layer, but does not enter the dermal layer or less enters the dermal layer as much as possible, and if the particle size of the selenium disulfide lotion is too small, the selenium disulfide lotion has too strong penetrating power to the skin and has the risk of toxic and side effects. Therefore, it is not feasible to solve the dispersibility and stability of the selenium sulfide simply by reducing the particle size of the selenium sulfide.
CN110772533A discloses a polyionic liquid containing selenium sulfide, which has no research on the dispersion state and foaming agent of the selenium sulfide, and the product has no capability of treating tinea versicolor caused by fungi. At present, no skin care product based on selenium sulfide exists in the market, and the product has the advantages of capability of effectively treating and relieving symptoms such as tinea versicolor, good skin affinity, easiness in washing, no side effect and good sensory experience of users. The development of the product has strong commercial value and clinical research significance.
Disclosure of Invention
The invention provides a selenium disulfide foam agent for skin care and a preparation method thereof, aiming at solving the technical defects that the existing selenium disulfide lotion for skin care is easy to discolor, uneven in dispersion, poor in sensory experience of users and the like.
In order to solve the technical problem, the invention provides a selenium disulfide foam agent for skin care, which comprises the following raw materials in percentage by mass: 0.5-3.0% of selenium disulfide micro powder, 12-20% of foaming agent, 2-5% of skin humectant, 1.5-3% of skin conditioner, 6-10% of foam propping agent, 1-2.5% of penetration enhancer, 0.5-2% of phosphatidylserine, 0.3-2% of amino acid, 0.03-0.1% of antioxidant, 5-8% of propellant and the balance of water.
Preferably, the selenium sulphide foam formulation of the invention is present in an amount of 1.3 to 1.8% by weight.
The foaming agent is widely applied to the industries of medicines and cosmetics, and is characterized by convenient use, low density, easier distribution on the epidermis than a lotion, no adhesion, guarantee of the adsorption or action time of the medicine, easy cleaning and strong compliance. In order to develop the selenium disulfide drug into the foaming agent, firstly, the problems of dispersion and stability of the selenium disulfide need to be solved, and secondly, the convenience degree and the sensory experience during use need to be considered. The selenium disulfide foaming agent provided by the invention has fine foam and good sensory experience for users. Through the selection of the components and the dosage in the formula, the selenium disulfide achieves the effects of caring skin, treating and/or relieving various skin symptoms with less dosage.
The skin symptoms comprise dermatitis, tinea and rash, especially skin symptoms caused by fungal infection; preferably, the skin condition is tinea versicolor.
The penetration enhancer comprises at least one of isopropyl myristate, medical-grade azone, menthol, bis-diethoxydiol cyclohexane 1, 4-dicarboxylate, propylene glycol methyl ether acetate, polycarboxylate and polyethylene glycol.
The invention adds phosphatidylserine as an auxiliary agent of the penetration enhancer, and the addition amount is 50-70wt% of the penetration enhancer. The inventors have unexpectedly discovered that the addition of phosphatidylserine, which acts in conjunction with a permeation enhancer, may further enhance the permeation of selenium disulfide into the epidermal skin, while phosphatidylserine alone does not have a permeation enhancing effect. Based on the incomplete absorption of the selenium disulfide lotion, the permeation enhancer reversibly alters the barrier properties of the outer layers of the stratum corneum, thereby driving the drug through the skin membrane via intracellular pathways. The invention can reduce the dosage of the selenium disulfide at the same time by combining the penetration enhancer and the penetration enhancer together to promote or enhance the intradermal penetration or delivery of the medicament. The inventor also finds that phosphatidylserine can help skin keep moisture and maintain proper oil-water balance. Phosphatidylserine is a penetration enhancer for further enhancing the permeability of selenium disulfide, and similar effects are not found in other phospholipid compounds, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and the like, and after the selenium disulfide is compounded with the penetration enhancer, the effect of obviously improving the penetration is not found. More preferably, the effect is most obvious when the phosphatidylserine and the isopropyl myristate are compounded and used together.
Furthermore, the selenium disulfide micro powder D90 is 4-50 μm, preferably 10-20 μm. Because of the limitation of the preparation process of the selenium disulfide micro powder at present, the particle size of the selenium disulfide in the market is generally more than 100 microns, and the particle size distribution is not uniform. The larger particle size and the wider particle size distribution are not beneficial to the dispersion and the stability of the selenium disulfide in the foaming agent; on the other hand, the selenium disulfide with large particle size is easy to gather, so that the selenium disulfide is not uniformly dispersed, and the risk of damage to hair and scalp due to local gathering is increased.
The invention controls the D90 of the selenium disulfide micro powder in a proper range, can solve the problem of uneven dispersion of the bulk drugs, and further prepares the foaming agent in a good suspension state. In addition, the particle size of the selenium disulfide is small, the adhesion between the medicine and the skin can be increased, the treatment time is prolonged, the bioavailability of the selenium disulfide is further improved, and the purpose of treatment can be achieved by a small dose of the selenium disulfide. However, the particle size of the selenium sulfide micro powder cannot be too small, and below 4 μm, the risk of toxic and side effects caused by selenium sulfide entering the dermis is high.
The selenium disulfide micro powder is prepared by the preparation method comprising the following steps: the selenium sulfide dry powder, water and glycerol are mixed according to the proportion of 1-1.2: 3-5: 1-2, then placing the mixture into an ultrafine grinder for grinding for 30-45 min, and controlling the particle size D90 to be 10-50 mu m to form the selenium disulfide micro powder.
The foaming agent is a compound of an anionic surfactant and an amphoteric surfactant according to the mass ratio of 3-7: 1. The anionic surfactant comprises at least one of lauryl alcohol ether sulfosuccinic acid monoester disodium salt, lauroyl sarcosine sodium, fatty alcohol sulfate, fatty acid monoglyceride sulfate, succinate sulfonate and lauryl sodium sulfate; the amphoteric surfactant comprises at least one of cocamidopropyl betaine, decyl hydroxypropyl sulfobetaine, dodecyl ethoxy sulfobetaine, hexadecyl hydroxypropyl sulfobetaine, and octadecyl ethoxy sulfobetaine. Within the above mixture ratio range, the anionic surfactant does not interact with the amphoteric surfactant to influence the stability of the system.
Even if the selenium disulfide micropowder with small particle size is insoluble substances with high density, aggregation and sedimentation exist, so that the phenomenon of uneven dispersion is generated, and the use experience of consumers is reduced. It is often necessary to add a thickener to inhibit agglomeration and settling of the selenium sulphide micropowder. However, the use of the thickener easily causes the foam of the foaming agent to be not fine and smooth enough, which leads to poor sensory experience of users, and the use of the thickener causes the foaming agent not to be easy to clean. In a preferred technical scheme of the invention, the surfactant is a compound of lauryl alcohol ether sulfosuccinic acid monoester disodium salt and cocamidopropyl betaine according to the mass ratio of 3-7: 1. The inventor finds that the compounded surfactant can stabilize the foaming agent, so that the selenium disulfide micro powder can be stably dispersed in the matrix without adding a thickening agent, and the defects of nonuniform and unstable dispersion are overcome; and the foam is fine and smooth, and the sensory experience of a user is improved.
The skin moisturizer is at least one selected from trehalose, beta-glucan and mannitol; the skin conditioning agent is at least one selected from sodium hyaluronate, panthenol and allantoin. The amino acid is at least one of proline, leucine and glycine, and can provide sufficient nutrition for skin.
The foam propping agent component is at least one selected from long-chain alkyl alcohol (octadecanol, hexadecanol), alcohol amine (triethanolamine, diethanolamine), paraffin, beeswax, cacao butter, fructus Citri Grandis butter, and cortex Phellodendri butter. Preferably the long-chain alkyl alcohol and the alcohol amine are compounded according to the mass ratio of 1-2: 1-2. The inventors have found that in accordance with the above formulated foam proppant, the foam is a friable and thermally stable foam when in use, i.e., it should be stable when released from a pressurized container and not crumble when exposed to the skin surface, but it should readily diffuse, decompose and be absorbed by the skin upon application of mild shear forces enabling prolonged foam time. The foam is a friable and thermally stable foam, i.e., it should be stable when released from a pressurized container and not crumble when exposed to the skin surface, but it should readily diffuse, disintegrate, and be absorbed by the skin upon application of mild shear forces.
The antioxidant is selected from a fat-soluble antioxidant and/or a water-soluble antioxidant, and the fat-soluble antioxidant is selected from at least one of dibutyl hydroxy toluene, vitamin E, carotenoid and astaxanthin; the water-soluble antioxidant is at least one selected from vitamin C and anthocyanin. The antioxidant is preferably astaxanthin and vitamin C according to the mass ratio of 1-3: 1-3. Selenium disulfide is oxidized to black during storage. And the proper amount of antioxidant is added to effectively prevent the selenium disulfide from discoloring. Fat-soluble astaxanthin and water-soluble vitamin C are selected to be compounded together, so that the antioxidant effect can be more effectively exerted, and the affinity to the skin and the skin care function are increased.
The propellant is non-freon propellant, such as at least one of tetrafluoroethane and heptafluoropropane. The advantages of the invention are also reflected in the selection of the propellant: the propellant used by some domestic and foreign manufacturers is a mixture of propane and butane, which is an extremely flammable and explosive substance, is unfavorable for production safety control, has high cost, and brings great hidden danger to daily use of people. The propellant of the invention is fluorinated alkane or chlorofluoro alkane, and can prepare good foaming agent. Considering that the chlorofluorocarbon propellant such as trichlorofluoromethane may cause serious damage to the earth's atmospheric ozone layer, it is not recommended to use it. Difluoroethane has properties similar to those of propane, butane and other alkanes or alkane mixture propellants, and is highly flammable and explosive. The best propellant choice is therefore to use tetrafluoroethane, heptafluoropropane or a mixture of the two.
Optionally, other adjuvants, such as 0.05-0.3% chelating agent, specifically selected from disodium edetate, may also be added into the selenium disulfide foam; 0.05-1% of essence, specifically at least one selected from lavender essence, peppermint essence, oriental cherry essence and osmanthus flower essence.
The preparation method of the selenium disulfide foaming agent provided by the invention is carried out according to the following steps:
s1, placing water in a reaction tank, heating to 60-80 ℃, adding a foam supporting component, a foaming agent and a chelating agent under a stirring state, and stirring to dissolve all the components to form a first mixture;
s2, dissolving an antioxidant in an alcohol-water solution, slowly adding the antioxidant solution, a penetration enhancer, phosphatidylserine, a skin conditioner, a skin humectant and amino acid into the first mixture, and stirring to dissolve all the components to obtain a second mixture;
s3, adding the selenium disulfide micro powder into the second mixture, and fully and uniformly stirring;
s4, adding a proper amount of essence and a pH regulator, supplementing water, continuing stirring and emulsifying for 1h, and cooling the tank body to room temperature to form a uniform suspension; sealing, pressing cover, and filling proper amount of propellant.
Further, in the preparation process, water is at least one of distilled water, deionized water and sterilized water, the amount of the water used in the step S1 is 40-60% of the total amount of the water, a reaction tank is a high-shear mixing dispersing emulsifying machine, the alcohol is ethanol in the step S2, the antioxidant is dissolved in an alcohol-water solution, the mass concentration of the alcohol in the alcohol-water solution is 50-70%, and the mass concentration of the antioxidant in the antioxidant solution is 10-20%.
The semi-finished product prepared by the invention is in a suspension state, the propellant is canned after being subpackaged by an aluminum can (epoxy phenolic resin coating), the ejected substance is orange foam, the foam is soft and exquisite, has certain strength, can be quickly and uniformly coated on the skin, has no foreign body sensation, and has good sensory experience of users. In the process of developing the selenium disulfide foaming agent, a high-low temperature test is adopted to investigate the stability of the preparation. And (3) placing the finished product at 30 ℃ for 24 hours, shaking, observing the foam state, then placing at 2-8 ℃ for 24 hours at low temperature, shaking, observing the foam state, and taking a cycle. Fifteen cycles were observed continuously. The results showed that the ejection foam state was still good after fifteen cycle examinations were completed.
The samples prepared according to the method were subjected to stability in use. The foam state is observed every day according to the single usage amount, the total amount of the foam is finally sprayed to be more than 90 percent until the foam is completely sprayed, and the foam state is good when the foam is sprayed every time.
Samples prepared according to this method were subjected to accelerated 6 month and long term 12 month stability studies. The results show that the formulation samples have very good stability and the product maintains a good foam state.
Drawings
FIG. 1 is a graph showing the stability test of the foaming agent of the present invention, wherein FIG. 1(A) shows the state where the foaming agent is sprayed out when stored for 0 day, and FIG. 1(B) shows the state where the foaming agent is sprayed out after stored for 60 days under accelerated conditions.
Detailed Description
The preparation and properties of the selenium sulphide foam formulation according to the invention are further illustrated by the following specific examples.
The selenium sulfide dry powder is purchased from Hubei Huishaopu pharmaceutical technology Co., Ltd, D90 about 130 μm.
The foaming quality of the foam was evaluated on 4 scales as follows: 1) and (3) excellent: the appearance is rich, the foam support is good, the foam structure is not contained, and the foam keeps very obvious creaminess when being diffused on the skin; 2) good: the appearance is rich, a small amount of micro-bubble structures are provided, and the film has certain creaminess when being spread on the skin; 3) in general: the visible foam cream is less, has a visible bubble structure, and becomes thin and wet when spread on the skin; 4) difference: no cream was seen, the foam was dry, large and weak bubbles, difficult to spread on the skin.
Preparation example 1
Mixing dry powder of selenium disulfide with D90 of about 130 μm, water and glycerol according to a mass ratio of 1: 3: 1, uniformly mixing, and crushing in an ultrafine crusher for 30min to finally obtain the selenium disulfide micro powder with the D90 of about 15 mu m.
Preparation example 2
Weighing the components according to the proportion, and preparing the selenium disulfide foaming agent according to the following steps:
s1, placing deionized water accounting for 60% of the total amount in a reaction tank of a high-shear mixing and dispersing emulsifying machine, heating to 60 ℃, adding a foam propping agent, a foaming agent and a chelating agent under a stirring state, and stirring to dissolve all components to form a first mixture;
S2, dissolving the fat-soluble antioxidant and/or the water-soluble antioxidant in 70% ethanol water solution to prepare antioxidant solution, slowly adding the antioxidant solution, the penetration enhancer, the skin conditioner, the skin humectant and the amino acid into the first mixture, and stirring to dissolve all the components to obtain a second mixture;
s3, adding the selenium disulfide micro powder into the second mixture, and fully and uniformly stirring;
s4, adding a proper amount of essence and a pH regulator, supplementing deionized water, continuing stirring and emulsifying for 1h, and cooling the tank body to room temperature to form a uniform suspension; sealing, pressing cover, and filling proper amount of propellant.
Examples in the following examples, the amounts of the respective raw materials were in mass%.
Example 1 study of antioxidants:
the selenium disulfide foaming agent is prepared according to the method of preparation example 2, and the formula of the foaming agent in percentage by mass is shown in the following table 1:
TABLE 1 foaming agent composition
Figure 761685DEST_PATH_IMAGE001
Compared with different antioxidant types, the astaxanthin has the optimal antioxidant effect, has a certain skin care function, but is expensive, and the selenium disulfide foaming agent can stably avoid blackening because the compound antioxidant of the astaxanthin and the vitamin C is used, and the fat-soluble antioxidant and the water-soluble antioxidant play a role together, so that the color of the foam can not change when the dosage is lower. Excessive antioxidant usage can lead to increased costs; the antioxidant is too little in dosage to effectively prevent the selenium disulfide from discoloring, so the optimal dosage of the antioxidant is 0.03-0.1%.
EXAMPLE 2 investigation of blowing agent
The selenium disulfide foaming agent is prepared according to the method of preparation example 2, and the formula of the foaming agent in percentage by mass is shown in the following table 2:
TABLE 2 foaming agent composition
Figure 209983DEST_PATH_IMAGE002
As can be seen from Table 2, the foaming agent is preferably used in an amount ranging from 8 to 15% to ensure good foaming and cleaning effects. Preferably, the anionic surfactant and the amphoteric surfactant are compounded according to a certain mass, particularly the compounding of the lauryl alcohol ether sulfosuccinic acid monoester disodium salt and the cocamidopropyl betaine in a ratio of 3-7:1, so that the optimal foaming effect can be achieved.
EXAMPLE 3 propellant Studies
The selenium disulfide foaming agent is prepared according to the method of preparation example 2, and the formula of the foaming agent in percentage by mass is shown in the following table 3:
TABLE 3 foaming agent composition
Figure 520879DEST_PATH_IMAGE003
The foam forming property is determined by the using amount of the propellant, the foam forming property is not facilitated by too little or too much propellant, good foam can be formed by 2-8% of the propellant, 5-8% is preferred, and the tetrafluoroethane and the heptafluoropropane are both suitable.
Example 4 investigation of the composition of foamed proppant
The selenium disulfide foaming agent is prepared according to the method of preparation example 2, and the formula of the foaming agent in percentage by mass is shown in the following table 4:
TABLE 4 foaming agent composition
Figure 945782DEST_PATH_IMAGE004
The foam supporting components and the using amount are researched, and the foaming quality is optimal when the long-chain alkyl alcohol (cetyl alcohol and/or stearyl alcohol) and the alcohol amine (triethanolamine and/or diethanolamine) are compounded to be used as the foam supporting agent. The foam support component has low dosage, poor foam support property, general quality and short foam collapse time, is not beneficial to fully infiltrating and contacting the skin, and reduces the treatment effect; excessive use amount can cause excessive foam support and partial hardness, and the foam has too long collapse time and is not washed away. The verification proves that the existence time of the foam is preferably 3-5 min.
Example 5 Effect of selenium disulfide particle size
The foam formulation was the same as formulation 4-1 of example 4 except that the selenium sulphide particle size was different. The results are shown in table 6 below:
TABLE 5 comparison of selenium disulfide foams of different particle sizes
Figure 25733DEST_PATH_IMAGE005
The particle size of the selenium disulfide dry powder is reduced after crystal form treatment, so that the uniform dispersion of the bulk drugs is facilitated, and the particle size D90 of the bulk drug selenium disulfide is controlled to be 10-50 μm, preferably 10-20 μm.
Example 6 enhancement of intradermal penetration or delivery of drugs
The selenium disulfide foam agent is prepared according to the method of preparation example 2, and the formula of the foam agent components in percentage by mass is shown in the following table 6. This example studies the effect of carrier on transdermal absorption by selenium disulfide foam via a 1.05mm thick synthetic silicone rubber membrane to simulate the mechanism of skin permeation by the foam of the present invention.
The specific operation is to establish a Franz diffusion cell, fix a silicon rubber membrane with the thickness of 1.05mm, and adopt a receiving cell which is normal saline with the same pH and the same osmotic pressure with human plasmaThe temperature of the water bath in the receiving tank was controlled at 32 ℃ and the temperature of the receiving tank was controlled at 32 ℃, and 0.1g of 1.30% selenium disulfide foam prepared according to the recipes 6-1 to 6-7 of example 6 was applied to a 1.05mm thick silicone rubber film with an area of 1cm2And after 24 hours of administration, the receiving solution is filtered by a microporous filter membrane, and the content of the selenium disulfide is detected by HPLC, and the transdermal rate is calculated.
TABLE 6 foaming agent composition
Figure 379354DEST_PATH_IMAGE006
As can be seen from the data in Table 6, the penetration enhancer and phosphatidylserine are used as the penetration enhancer auxiliary agent, so that the transdermal rate of the selenium disulfide can be obviously improved, and the curative effect can be ensured while the content of the selenium disulfide is reduced. The inventor surprisingly found that the combination of phosphatidylserine and isopropyl myristate was most significant in enhancing penetration. Other conventional penetration enhancers are matched with phosphatidylserine, so that the penetration enhancing effect is not obviously improved. Phosphatidylserine alone does not promote penetration.
EXAMPLE 7 study of stability
The selenium sulfide foaming agent of formula 4-1 was tested and the results are shown in table 7 below:
TABLE 7 selenium disulfide foam index
Figure 177546DEST_PATH_IMAGE007
Accelerated tests (40 ℃, 75% RH) and long-term tests (25 ℃, 60% RH) were carried out to test the stability, the results of which are shown in table 8 below:
table 8 stability test data
Figure 642025DEST_PATH_IMAGE008
The stability test results in table 8 demonstrate that the selenium disulfide foam prepared by the present invention has good stability after accelerated for 6 months and long-term 12 months, and does not affect the foaming condition of the foam. The selenium disulfide has no agglomeration or sedimentation phenomenon.
FIG. 1 is a graph showing the stability test of selenium sulfide foams of formula 4-1, wherein FIG. 1(A) shows the state of the sprayed foam when the foam is stored for 0 day, and FIG. 1(B) shows the state of the sprayed foam after the foam is stored for 60 days under accelerated conditions. The selenium sulfide foaming agent prepared by the invention is stored for 6 months under an accelerated condition, has no obvious adverse effect on the sprayed foam state, meets the actual use requirement, and is stable.
Application example
Please refer to 50 patients suffering from tinea versicolor, wherein the patients use the selenium disulfide foam (selenium disulfide content is 1.30wt%) with the formula 4-1 of the invention to clean the affected parts every day, the retention time of the foam on the skin of the patients is controlled to be 60s, the affected parts are continuously massaged, and then the foam is washed off by clean water for 1 month, so as to investigate the symptom relief and treatment conditions of the tinea versicolor of the patients. The results are shown in table 9 below:
TABLE 9 prevention and treatment of tinea versicolor with selenium disulfide foam
Figure 842063DEST_PATH_IMAGE009

Claims (8)

1. The selenium disulfide foam agent for skin care is characterized by comprising the following raw materials in percentage by mass: 0.5-3.0% of selenium disulfide micro powder, 12-20% of foaming agent, 2-5% of skin humectant, 1.5-3% of skin conditioner, 6-10% of foam propping agent, 1-2.5% of penetration enhancer, 0.5-2% of phosphatidylserine, 0.3-2% of amino acid, 0.03-0.1% of antioxidant, 5-8% of propellant and the balance of water;
the penetration enhancer is at least one selected from isopropyl myristate, medical grade azone and menthol; the addition amount of the phosphatidylserine is 50-70wt% of the penetration enhancer;
the selenium disulfide micro powder D90 is 4-50 μm;
the foam propping agent is a compound of long-chain alkyl alcohol and alcohol amine according to the mass ratio of 1-2: 1-2; the long-chain alkyl alcohol is selected from hexadecanol and/or octadecanol, and the alcohol amine is selected from triethanolamine and/or diethanolamine.
2. The selenium disulfide foam for skin care according to claim 1, wherein the foaming agent is a compound of an anionic surfactant and an amphoteric surfactant in a mass ratio of 3-7: 1; the anionic surfactant comprises at least one of lauryl alcohol ether sulfosuccinic acid monoester disodium salt, sodium lauroyl sarcosinate, fatty alcohol sulfate, fatty acid monoglyceride sulfate and succinate sulfonate; the amphoteric surfactant comprises at least one of cocamidopropyl betaine, decyl hydroxypropyl sulfobetaine, dodecyl ethoxy sulfobetaine, hexadecyl hydroxypropyl sulfobetaine, and octadecyl ethoxy sulfobetaine.
3. A selenium sulphide foam for skin care according to claim 2 wherein the surfactant is a combination of lauryl alcohol ether sulphosuccinate monoester disodium salt and cocamidopropyl betaine in a mass ratio of 3-7: 1.
4. The selenium disulfide foam for skin care of claim 1, wherein the skin moisturizer is selected from at least one of trehalose, β -glucan, mannitol; the skin conditioning agent is at least one selected from sodium hyaluronate, panthenol and allantoin; the amino acid is at least one of proline, leucine and glycine; the propellant is a non-freon propellant.
5. The selenium disulfide foam for skin care according to claim 1, wherein the antioxidant is selected from a fat-soluble antioxidant and/or a water-soluble antioxidant, the fat-soluble antioxidant being selected from at least one of dibutylhydroxytoluene, vitamin E, a carotenoid, astaxanthin; the water-soluble antioxidant is at least one selected from vitamin C and anthocyanin.
6. The selenium disulfide foam for skin care according to claim 5, wherein the antioxidant is astaxanthin and vitamin C in a mass ratio of 1-3: 1-3.
7. A method of forming a selenium sulphide foam formulation as claimed in any one of claims 1 to 6 comprising the steps of:
s1, placing water in a reaction tank, heating to 60-80 ℃, adding a foam propping agent, a foaming agent and a chelating agent under a stirring state, and stirring to dissolve all components to form a first mixture;
s2, dissolving an antioxidant in an alcohol-water solution, slowly adding the antioxidant solution, a penetration enhancer, phosphatidylserine, a skin conditioner, a skin humectant and amino acid into the first mixture, and stirring to dissolve all the components to obtain a second mixture;
s3, adding the selenium disulfide micro powder into the second mixture, and fully and uniformly stirring;
s4, adding a proper amount of essence and a pH regulator, supplementing water, continuously stirring and emulsifying for 1h, and simultaneously cooling the tank body to room temperature to form a uniform suspension; sealing, capping and filling proper amount of propellant.
8. Use of a selenium sulphide foam formulation as claimed in any one of claims 1 to 6 in the manufacture of a medicament for the treatment of a skin condition, wherein the skin condition comprises dermatitis, tinea, rashes.
CN202210387189.9A 2022-04-14 2022-04-14 Selenium disulfide foam agent for skin care and preparation method thereof Active CN114452257B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210387189.9A CN114452257B (en) 2022-04-14 2022-04-14 Selenium disulfide foam agent for skin care and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210387189.9A CN114452257B (en) 2022-04-14 2022-04-14 Selenium disulfide foam agent for skin care and preparation method thereof

Publications (2)

Publication Number Publication Date
CN114452257A CN114452257A (en) 2022-05-10
CN114452257B true CN114452257B (en) 2022-06-14

Family

ID=81418528

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210387189.9A Active CN114452257B (en) 2022-04-14 2022-04-14 Selenium disulfide foam agent for skin care and preparation method thereof

Country Status (1)

Country Link
CN (1) CN114452257B (en)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2728163A1 (en) * 1994-12-20 1996-06-21 Oreal STABLE COSMETIC, DERMATOLOGICAL OR PHARMACEUTICAL COMPOSITION CONTAINING SELENIUM DISULPHIDE AND AT LEAST ONE ZINC SALT
FR2813189B1 (en) * 2000-08-31 2003-02-28 Oreal COSMETIC FOAMING CREAM FOR THE TREATMENT OF OILY SKIN
CN105943534A (en) * 2008-04-15 2016-09-21 萨可德生物科学公司 Topical LFA-1 antagonists for use in localized treatment of immune related disorders
EP2789369B1 (en) * 2013-04-14 2018-06-06 Symrise AG A composition for lightening skin and hair
CN110772533A (en) * 2019-11-22 2020-02-11 上海心动能科技有限公司 Multi-ion liquid for treating onychomycosis and preparation method and application thereof

Also Published As

Publication number Publication date
CN114452257A (en) 2022-05-10

Similar Documents

Publication Publication Date Title
JP4758915B2 (en) Multilamellar liposome and production method thereof
JP4203394B2 (en) Micronized liposomes containing a high concentration of triterpenoid and method for producing the same
TWI325325B (en) Nanoliposome using esterified lecithin and method for preparing the same, and composition for preventing or treating skin diseases comprising the same
TWI417112B (en) Emulsified composition
CA2406570C (en) Dermal compositions containing coenzyme q as the active ingredient
PT1853303E (en) Stabilized compositions for topical administration and methods of making same
CN114146009B (en) DHA anti-aging anti-inflammatory nano composition and preparation method and application thereof
CN110302087B (en) Repairing composition, application and skin care composition containing repairing composition
CN109069418A (en) topical composition comprising tacrolimus
TWI236911B (en) Stabilized whitening compositions and methods of preparing same
US20110236503A1 (en) Topical Skincare Composition
KR20180057714A (en) Non-rinse chemical foams containing triparotene, and uses thereof in the treatment of acne
CN114452257B (en) Selenium disulfide foam agent for skin care and preparation method thereof
KR101761005B1 (en) Cosmetic composition containing non-toxic sulfur for sikn moisture, anti-inflammatory and immune enhancement and manufacturing the same
CN107595766B (en) Lidocaine microemulsion gel and preparation method thereof
JPH04338311A (en) Humectant
CN114452228B (en) Selenium disulfide foaming agent for hair washing and preparation method thereof
EP2726071B1 (en) Topical formulations including lipid microcapsule delivery vehicles and their uses
CN115554243B (en) Minocycline foam for treating acne rosacea
KR102632236B1 (en) Liposome complex and cosmetic composition for improving skin condition comprising the same
KR20160075245A (en) Composition for forming cubic phase structure, cosmetic composition for using the same and method for manufacturing cosmetic composition
CN115463091B (en) Minocycline foaming agent with improved stability
Priyanka et al. Use of novel penetration enhancers and techniques in tdds
JP2003212751A (en) Gel composition and oil-in-water (o/w) composition
JP3658114B2 (en) Topical skin preparation

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant