CN117379364A - Skin scald repair gel and preparation method and application thereof - Google Patents

Skin scald repair gel and preparation method and application thereof Download PDF

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Publication number
CN117379364A
CN117379364A CN202311617754.7A CN202311617754A CN117379364A CN 117379364 A CN117379364 A CN 117379364A CN 202311617754 A CN202311617754 A CN 202311617754A CN 117379364 A CN117379364 A CN 117379364A
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parts
skin
gel
water
mixture
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李娟�
姚遥
孙美霞
贾傲
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Ningxia Medical University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7084Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
    • 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
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to the technical field of skin repair, in particular to a skin scald repair gel and a preparation method and application thereof. The invention provides a skin scald repair gel, which comprises the following components in parts by weight: 1 to 10 parts of nicotinamide adenine dinucleotide, 9400.4 to 1.6 parts of carbomer, 4 to 16 parts of glycerol, 2 to 10 parts of propylene glycol, 0.3 to 0.7 part of potassium sorbate, 2 to 5 parts of triethanolamine and 25 to 2.0 parts of tween-800.4; 54.7 to 89.9 portions of water. The gel prepared by the invention has obvious repairing effect on the wound surface of the skin scald, is not stimulated to the skin and has no sensitization, and the preparation method is simple and easy to operate.

Description

Skin scald repair gel and preparation method and application thereof
Technical Field
The invention relates to the technical field of skin repair, in particular to a skin scald repair gel and a preparation method and application thereof.
Background
Skin acts as a protective barrier and is the largest organ of the human body, and skin burns occur in daily life and may be life-threatening if not properly treated. The healing period of the skin scald is longer, if the treatment is not in time, the wound surface of the scald is difficult to recover, even permanent scars are left, and the appearance change and the skin dysfunction caused by the scars generated by the skin scald can have a certain influence on the life quality of people, even a certain psychological shadow is left for patients.
For repairing the scalded skin wound, the medicine can be smeared and administrated through external medicines, and the medicine is smeared on the wound surface, so that the medicine can directly act on the scalded part, the curative effect is enhanced, and the adverse reaction is less. At present, the silver sulfadiazine cream has wide application on scalds, has strong antibacterial and anti-inflammatory effects, but generates certain irritation to skin, is easy to cause pain, and has certain influence on wound healing. In addition, ointment preparations for scalds are also prone to adverse reactions such as fever. Therefore, the development of the low-irritation and high-safety scald repair drug is a research direction of scald repair products.
Disclosure of Invention
The invention aims to provide the skin scald repair gel which has no irritation to skin, has obvious repair effect on the wound surface of scalded skin and has a simple preparation method.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a skin scald repair gel, which comprises the following components in parts by weight: 1 to 10 parts of nicotinamide adenine dinucleotide, 9400.4 to 1.6 parts of carbomer, 4 to 16 parts of glycerol, 2 to 10 parts of propylene glycol, 0.3 to 0.7 part of potassium sorbate, 2 to 5 parts of triethanolamine and 0.4 to 2.0 parts of tween-80; 54.7 to 89.9 portions of water.
Preferably, the composition comprises the following components in parts by weight: 4-7 parts of nicotinamide adenine dinucleotide, 9400.8-1.2 parts of carbomer, 7-13 parts of glycerol, 4-8 parts of propylene glycol, 0.4-0.6 part of potassium sorbate, 3-4 parts of triethanolamine, 0.8-1.6 parts of tween-80 and 64.6-80.0 parts of water.
Preferably, the composition comprises the following components in parts by weight: 5.5 parts of nicotinamide adenine dinucleotide, 9401.0 parts of carbomer, 10 parts of glycerol, 6 parts of propylene glycol, 0.5 part of potassium sorbate, 3.5 parts of triethanolamine, 1.2 parts of tween-80 and 72.3 parts of water.
The invention also provides application of the skin scald repair gel in preparing a medicine for repairing skin scald.
The invention also provides a preparation method of the skin scald repair gel, which comprises the following steps:
(1) Mixing carbomer 940 with water, and standing to obtain gel mixture;
(2) Mixing nicotinamide adenine dinucleotide, tween-80, glycerol, propylene glycol, potassium sorbate and the gel mixture with water to obtain a mixture;
(3) Adding triethanolamine into the mixture, adjusting the pH of the mixture, and adding the rest water to obtain the skin scald repair gel.
Preferably, in the step (1), the addition amount of the water is 50% -70% of the total amount of the water.
Preferably, the temperature of the mixing in step (1) is 50 to 70 ℃.
Preferably, the standing time is 2 to 4 hours;
preferably, in the step (2), the water is added in an amount of 25% to 45% of the total amount of water.
The invention has the beneficial effects that:
(1) The skin scald repair gel comprises the components of the carbomer 940, nicotinamide adenine dinucleotide, propylene glycol, glycerol, potassium sorbate and triethanolamine. It has obvious repairing effect on the wound surface of skin scald, no irritation to skin and no sensitization.
(2) The preparation method of the skin scald repair gel has simple steps and is easy to operate.
Drawings
FIG. 1 shows the results of the healing rate test.
Detailed Description
The invention provides a skin scald repair gel, which comprises the following components in parts by weight: 1 to 10 parts, preferably 4 to 7 parts, more preferably 5.5 parts of nicotinamide adenine dinucleotide;
9400.4 to 1.6 parts, preferably 0.8 to 1.2 parts, more preferably 1.0 part of carbomer;
4 to 16 parts of glycerin, preferably 7 to 13 parts, and more preferably 10 parts;
2 to 10 parts, preferably 4 to 8 parts, more preferably 6 parts of propylene glycol;
potassium sorbate 0.3 to 0.7 part, preferably 0.4 to 0.6 part, more preferably 0.5 part;
2 to 5 parts of triethanolamine, preferably 3 to 4 parts, more preferably 3.5 parts;
tween-80 0.4 to 2.0 parts, preferably 0.8 to 1.6 parts, further preferably 1.2 parts;
54.7 to 89.9 parts of water, preferably 64.6 to 80.0 parts, and more preferably 72.3 parts.
In the invention, the nicotinamide adenine dinucleotide can stimulate the epidermis differentiation and wound healing, has obvious repairing effect on the scalded skin wound surface, and can not generate irritation to the skin when the nicotinamide adenine dinucleotide is externally used; propylene glycol has the advantages of improving the transdermal absorption performance of each component, changing the barrier function of the skin stratum corneum, facilitating the rapid flow of each component, and promoting the rapid healing of wound surfaces; the glycerol is beneficial to avoiding the loss of water in the gel; because the water content in the gel is high, the gel is easy to mildew, and therefore, a certain amount of preservative, potassium sorbate, is also added in the gel; carbomer 940 has a clear appearance, no greasy feel, proper viscosity, good spreadability, no irritation to skin and mucous membrane, good adhesiveness and uniform distribution of the drug on the skin, and in addition, it dries faster and is easy to elute;
the invention also provides application of the skin scald repair gel in preparing a medicine for repairing skin scald.
The invention also provides a preparation method of the skin scald repair gel, which comprises the following steps:
(1) Mixing carbomer 940 with water, and standing to obtain gel mixture;
(2) Mixing nicotinamide adenine dinucleotide, tween-80, glycerol, propylene glycol, potassium sorbate and the gel mixture with water to obtain a mixture;
(3) Adding triethanolamine into the mixture, adjusting the pH of the mixture, and adding the rest water to obtain the skin scald repair gel.
In the present invention, in step (1), carbomer 940 is added in portions during mixing of carbomer 940 with water;
in the invention, in the step (1), the addition amount of the water accounts for 50-70 percent, preferably 60 percent of the total amount of the water;
in the present invention, the temperature of the mixing in step (1) is 50 to 70 ℃, preferably 60 ℃;
in the invention, the standing time is 2-4 hours, preferably 3 hours;
in the present invention, in the step (2), the amount of the water added is 25% to 45% of the total amount of water, preferably 35%.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
The rats used in the experimental example of the present invention are SPF-grade SD rats, male, weight 180-220 g; healthy adult rabbits, male and female rabbits are half, and the weight is 1.8-2.4 kg; healthy adult guinea pigs, male and female half, have a body weight of 300-350 g. Rats, rabbits and guinea pigs were purchased from the university animal center of Ningxia medical science
Example 1A skin Scald repair gel
(1) Uniformly adding 0.7g of carbomer 940 into 47g of pure water in a water bath state at 60 ℃ in a divided manner, mixing, uniformly stirring, and standing for 2 hours to obtain a gel mixture;
(2) Mixing 5.0g of nicotinamide adenine dinucleotide, 1.2g of tween-80, 8.0g of glycerol, 2.0g of propylene glycol, 0.5g of potassium sorbate, the gel mixture of step (1) with 27g of water to obtain a mixture;
(3) 3.5g of triethanolamine is slowly added into the mixture, the pH is regulated, 5.1g of water is added, and the mixture is stirred uniformly, thus obtaining the skin scald repair gel.
Example 2A skin Scald repair gel
(1) Uniformly adding 0.7g of carbomer 940 into 50g of pure water in a water bath state at 60 ℃ for mixing, uniformly stirring, and standing for 3 hours to obtain a gel mixture;
(2) Mixing 3.0g of nicotinamide adenine dinucleotide, 1.0g of tween-80, 7.0g of glycerol, 4.0g of propylene glycol, 0.5g of potassium sorbate, and the gel mixture of step (1) with 25g of water to obtain a mixture;
(3) Slowly adding 2.5g of triethanolamine into the mixture, regulating pH, adding 6.3g of water, and stirring uniformly to obtain the skin scald repairing gel.
Example 3A skin Scald repair gel
(1) Uniformly adding 1.0g of carbomer 940 into 42g of pure water in a water bath state at 60 ℃ for mixing, uniformly stirring, and standing for 3 hours to obtain a gel mixture;
(2) Mixing 6.0g of nicotinamide adenine dinucleotide, 1.5g of tween-80, 9.0g of glycerol, 3.0g of propylene glycol, 0.4g of potassium sorbate, and the gel mixture of step (1) with 28g of water to obtain a mixture;
(3) 3.8g of triethanolamine is slowly added into the mixture, the pH is regulated, 5.3g of water is added, and the mixture is stirred uniformly, thus obtaining the skin scald repair gel.
Example 4A skin Scald repair gel
(1) Uniformly adding 1.3g of carbomer 940 into 46g of pure water in a water bath state at 60 ℃ for mixing, uniformly stirring, and standing for 3 hours to obtain a gel mixture;
(2) Mixing 7.0g of nicotinamide adenine dinucleotide, 2.0g of tween-80, 5.0g of glycerol, 6.0g of propylene glycol, 0.6g of potassium sorbate, and the gel mixture of step (1) with 24g of water to obtain a mixture;
(3) Slowly adding 4.5g of triethanolamine into the mixture, adjusting pH, adding 3.6g of water, and stirring uniformly to obtain the skin scald repairing gel.
Example 5A skin Scald repair gel
(1) Uniformly adding 1.0g of carbomer 940 into 40g of pure water in a water bath state at 60 ℃ for mixing, uniformly stirring, and standing for 4 hours to obtain a gel mixture;
(2) Mixing 5.0g of nicotinamide adenine dinucleotide, 1.2g of tween-80, 10.0g of glycerol, 4.0g of propylene glycol, 0.5g of potassium sorbate, and the gel mixture of step (1) with 30g of water to obtain a mixture;
(3) 3.5g of triethanolamine is slowly added into the mixture, the pH is regulated, 4.8g of water is added, and the mixture is stirred uniformly, thus obtaining the skin scald repair gel.
Experimental example 1 pharmacodynamic experiment
Rats were randomly divided into 4 groups: skin scald repair gel administration group (NAD+ group), sulfadiazine silver cream positive drug group [ SSD group (positive control) ], blank gel matrix group (gel matrix is prepared according to the method of example 5, wherein the components do not contain nicotinamide adenine dinucleotide, matrix group), and model group, 8 rats of each group are molded with metal weights except for normal group. The molding method comprises the following steps:
after shallow anesthesia of the rats, the metal weights were pre-placed in boiling water for 30min. The mixture is quickly wiped and dried on the back of a rat after being taken out, the mixture lasts for 15 seconds, the wound surface of the skin scald is formed, the size of the wound surface is 1.5cm multiplied by 1.5cm, and then 5ml of physiological saline is injected into the abdominal cavity to resist shock.
The NAD+ group uniformly smears 0.3ml of the skin scald repair gel described in the embodiment 5 on each scald wound surface, the SSD group (positive control) smears sulfadiazine silver cream on each scald wound surface according to the specification, the blank gel matrix group uniformly smears 0.3ml of blank gel matrix on each scald wound surface, and the model group smears 0.3ml of physiological saline on each scald surface. The medicine is taken once a day for 2 weeks continuously, the healing condition of the skin scalds of the 0 th, 3 th, 5 th, 8 th, 11 th and 14 th days after the scalds is observed, the wound surface area at each time point is assessed according to the observed crusting degree of the scalded wound surface, the scar formation, the healing area and the like, and the healing rate of the scalded wound area is taken as an index. And detecting the treatment effect of each group on the skin scald of the rat caused by the metal weights. The results of the detection are shown in Table 1 and FIG. 1.
Wherein, the calculation formula of the healing rate of the scalded wound area is as follows:
healing rate (%) = (initial area of wound surface-area of wound surface at each time point)/(initial area of wound surface x 100%).
TABLE 1 results of healing Rate measurements
As can be seen from fig. 1 and table 1, the skin scald repair gel described in example 5 can significantly promote healing of a wound surface of a rat scald.
Experimental example 2 safety experiment
1. Skin irritation test
The hairs on the two sides of the spine of 8 rabbits are removed 24 hours before the experiment, so that the epidermis cannot be damaged. The skin scald repair gel described in example 1 was smeared on the upper right side of the dehairing site of a rabbit, a blank gel matrix (gel matrix was prepared according to the method of example 1, wherein the components do not contain nicotinamide adenine dinucleotide, blank control group) was smeared on the upper left side of the dehairing site, physiological saline was smeared on the rest of the sites, the moisturizing was covered with a preservative film, then gauze was added to cover and fixed with a non-irritating adhesive tape and bandage, and after 1h, 24h, 48h and 72h, the local skin reaction of the rabbit was observed.
After skin irritation test, observing for 1h, 24h, 48h and 72h, the skin scald repair gel of the embodiment 1 is smeared on the site without adverse reactions such as erythema, edema and the like. The skin scald repair gel is free from skin irritation reaction.
2. Skin allergy test
24 hours before the experiment, the hairs on the two sides of the spinal column of 12 guinea pigs are removed, and the epidermis can not be damaged. Guinea pigs were randomly divided into 3 groups: (1) skin scald repair gel administration group (nad+ group): the skin scald repair gel described in example 1 was applied to the right side of the hairline site of guinea pigs by 0.2ml; (2) 1% of 2, 4-dinitrochlorobenzene administration group (positive control group): 1% of 2, 4-dinitrochlorobenzene is smeared on the right side of a hairremoving part of a guinea pig, and the smearing amount is 0.2ml; (3) blank gel matrix group (gel matrix was not prepared according to the method of example 1, wherein the components did not contain nicotinamide adenine dinucleotide, blank control group): the blank gel matrix was applied to the right side of the guinea pig depilatory site, at 0.2ml. After the skin is fixed for 6 hours by using weighing paper and gauze, gel remained on the surface of the skin is removed by using warm water, allergic reactions such as erythema, edema and the like are observed at the smearing positions for 24 hours, 48 hours and 72 hours, and the average integral and the sensitization rate of the allergic reactions are taken as judging standards to detect the skin allergy of the skin scald repair gel. The test results are shown in Table 2.
The average integral of anaphylactic reaction and the sensitization rate are calculated as follows:
average integral of allergic response (score) = (total erythema plus total edema)/(total animals tested);
sensitization rate (%) = number of animals with skin erythema and edema +.f. total number of animals tested x 100%.
TABLE 2 skin allergy test results
As is clear from Table 2, the guinea pigs did not develop allergic reactions after the skin scald repair gel described in example 1 was applied. The skin scald repair gel disclosed by the invention has no sensitization.
As can be seen from the above examples, the invention provides a skin scald repair gel, and a preparation method and application thereof, and the prepared gel has obvious repair effect on skin scald wound surface, is not stimulated to skin, has no sensitization, and has simple preparation method and easy operation.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.

Claims (9)

1. The skin scald repair gel is characterized by comprising the following components in parts by weight: 1 to 10 parts of nicotinamide adenine dinucleotide, 9400.4 to 1.6 parts of carbomer, 4 to 16 parts of glycerol, 2 to 10 parts of propylene glycol, 0.3 to 0.7 part of potassium sorbate, 2 to 5 parts of triethanolamine and 0.4 to 2.0 parts of tween-80; 54.7 to 89.9 portions of water.
2. The skin scald repair gel of claim 1, comprising the following components in parts by weight: 4 to 7 parts of nicotinamide adenine dinucleotide, 9400.8 to 1.2 parts of carbomer, 7 to 13 parts of glycerol, 4 to 8 parts of propylene glycol, 0.4 to 0.6 part of potassium sorbate, 3 to 4 parts of triethanolamine, 800.8 to 1.6 parts of tween-and 64.6 to 80.0 parts of water.
3. The skin scald repair gel of claim 1, comprising the following components in parts by weight: 5.5 parts of nicotinamide adenine dinucleotide, 9401.0 parts of carbomer, 10 parts of glycerol, 6 parts of propylene glycol, 0.5 part of potassium sorbate, 3.5 parts of triethanolamine, 1.2 parts of tween-80 and 72.3 parts of water.
4. Use of the skin scald repair gel as claimed in any one of claims 1 to 3 for preparing a medicament for repairing a skin scald.
5. A method for preparing a skin scald repair gel as claimed in any one of claims 1 to 3, comprising the steps of:
(1) Mixing carbomer 940 with water, and standing to obtain gel mixture;
(2) Mixing nicotinamide adenine dinucleotide, tween-80, glycerol, propylene glycol, potassium sorbate and the gel mixture with water to obtain a mixture;
(3) Adding triethanolamine into the mixture, adjusting the pH of the mixture, and adding the rest water to obtain the skin scald repair gel.
6. The method according to claim 5, wherein in the step (1), the water is added in an amount of 50% to 70% of the total amount of water.
7. The method according to claim 6, wherein the temperature of the mixing in the step (1) is 50 to 70 ℃.
8. The method according to claim 7, wherein the time for the standing is 2 to 4 hours.
9. The method according to claim 8, wherein the water is added in an amount of 25% to 45% of the total amount of water in step (2).
CN202311617754.7A 2023-11-29 2023-11-29 Skin scald repair gel and preparation method and application thereof Pending CN117379364A (en)

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