KR20150130618A - Hydrogel Burn Wound Treatment of Aerosol Spray Type - Google Patents

Abstract

The present invention relates to a hydrogel agent of an aerosol spray type for treating burn injuries and, more specifically, to a hydrogel agent of an aerosol spray type for treating burn injuries comprising: 27 to 94 wt% of a coolant, 5 to 20 wt% of a cooling propellant, 0.1 to 50 wt% of a cooling germicide and 0.5 to 3 wt% of a thickening agent.

Description

[0001] The present invention relates to an aerosol spray type hydrogel,

The present invention relates to an aerosol spray type hydrogel burn treatment agent, and more particularly, to an burn treatment agent which improves the persistence of the initial prescription effect through flow improvement.

 An image can be classified into a hot-water image, a contact image, a flame image, a scintillation image, a chemical image, an electric image, and a radiographic image depending on the damage mechanism. Deep 2nd degree burns and third degree burns, in which most protective epithelial layers and almost all dermal layers are destroyed, can quickly catch bacteria and cause infections.

 Prevention of infection in burns is a common problem in nursing burn patients. Infection in most burns can quickly progress to life-threatening sepsis if untreated.

Therefore, it is a problem to rapidly treat the affected part of the image, and U.S. Patent No. 3,761,590 describes a method of producing a thick creamy ointment containing silver sulfadiazine useful for conventional burn treatment.

 However, these cream products use only sterilization technology to apply the affected part. In addition, this type of drug administration operation is very time consuming and may allow for the possibility of cross-contamination between patients due to multiple uses of the same container. Cross-contamination usually prevents the doctor from prescribing the product to the patient, and is used clinically only after each treatment rather than at home. Therefore, even if the patient has a bad smell, there is a risk of infection during the application of the cream. Thus, there is a clear need in the art to develop formulations that are inexpensive, less painful, easy to use, transparent and not cross-contaminated for burn therapy. Therefore, in order to overcome the risk of cross - contamination, the need for spray - type instruments has increased and a spray - type aerosol method has been developed to solve this problem.

  U.S. Patent No. 5,143,717 discloses certain aerosol formulations of antibiotics containing silver sulfadiazine in a cream base as a topical water-soluble blowing agent. (2) the activity of the aerosol product needs to be lined inside the aerosol or have a protective coating to stabilize the compound; (3) the sensitive wound area (4) the foam can easily slide without being adhered to the wound area when contacted with the patient, reducing the concentration of the antimicrobial agent in the treatment position and not being applied properly There is a disadvantage that the antimicrobial foam can not be held in place.

 In order to compensate for this, a method of spraying in non-aerosol form such as a gel has been devised, and U.S. Patent No. 4,803,066 describes a number of suitable gelling agents, but no description of a spraying hydrogel is mentioned. On the other hand, in U.S. Patent No. 4,551,139, when the cream is pushed out of the folding bag into the outlet, the cream is delivered to the sanitary spray nozzle by a sanitary pump operated with compressed air. However, the present invention does not mention specific high viscosity cream formulations.

 In addition, in Publication No. 2001-0012464, a gel or cream lotion formulation is used as a trigger device to overcome the drawbacks of the conventional spray method. However, the present invention has difficulties in terms of the inconvenience due to the insufficient spraying and spraying range, the problem of the duration of spraying due to the lack of propellant, and the control of the application of a certain thickness depending on the size of the affected part.

Finally, there is a cooling effect to be considered as an image treatment agent. An image is a temperature impairment at the point of symmetry of the phase. That is, a state in which tissue cells and tissue structures lose their integrity and are destroyed by an insatiable level of excessive heat load. As with most damage procedures, the degree of initial treatment of burn injuries has a significant impact on the survival rate and the incidence of complications. Therefore, if an initial burn occurs, the heat remaining on the body surface must be removed promptly to prevent further burns or other tissue damage. In case of thermotherapy, it is possible to expect the effect of cold water / cooling treatment by emergency treatment, that is, it quickly removes body heat, reduces edema, reduces tissue damage and improves wound healing, thereby reducing scarring, It is recommended by several imaging associations to promote circulation and prevent shock. Therefore, since the effect of the image treatment by cold water and cooling has been proved, development of an effective cooling agent is required. In order to prevent infections caused by inadequate mobility of the patient and continuous or irreversible tap water, the invention of burn treatment is needed. In addition, since the existing therapeutic agent has insufficient cooling effect or is tubular, there is a possibility of secondary infection that may occur when contaminants are introduced into the container every time it is used. Therefore, there is a need to develop an aerosol spray type material which is excellent in cooling effect and does not cause infection due to container contamination during injection.

 In order to solve the above problems, the present invention is to provide an image treatment agent capable of rapid spray application in initial image treatment.

Further, the present invention is to provide an improved burn treatment agent so that the applied burn treatment agent can be continuously persisted in the lesion.

  In order to achieve the above object, the present invention provides an aerosol spray type hydrogel comprising 27 to 94% by weight of a base coolant, 5 to 20% by weight of a cooling promoter, 0.1 to 50% by weight of a cooling sterilizer, and 0.5 to 3% Thereby providing an image therapeutic agent.

The present invention also provides an aerosol spray type hydrogel burn treatment agent comprising 0.01 to 1 part by weight of a pH adjusting agent or 0.01 to 3 parts by weight of a fungicide per 100 parts by weight of the image processing agent.

Further, the present invention provides an aerosol spray type hydrogel burn treatment agent, wherein the bass coolant may include water or purified water, the cooling propellant may include DME gas, and the cooling sterilizing agent may include ethanol.

In the present invention, it is preferable that the thickening agent includes at least one of cellulose, gum, seaweed (alginic acid, carrageenan), protein (gelatin), alkali swellable type and urethane associative type And an aerosol spray type hydrogel burn treatment agent.

In addition, the present invention is characterized in that the fungicide includes at least one of tea tree oil, lavender, German Chamomile and Roman camomile, PHMB (polyhexamethylene biguanide), and silver antimicrobial agent Wherein the aerosol-spray-type hydrogel-based therapeutic agent is an aerosol spray-type hydrogel-based therapeutic agent.

Also, the present invention provides an aerosol spray type hydrogel burnable therapeutic agent to which 0.08 to 0.13 parts by weight of a preservative is added to 100 parts by weight of the above-mentioned burn agent.

Also, the present invention is characterized in that the preservative comprises at least one of methylparaben, propylparaben, benzyl alcohol, benzoic acid, sodium benzoate, potassium benzoate, sorbic acid, sodium sorbate, potassium sorbate and phenylethyl alcohol And an aerosol spray type hydrogel burn treatment agent.

In addition, the present invention provides an aerosol spray type hydrogel burnable therapeutic agent characterized in that the range of viscosity after spraying the therapeutic agent is in the range of 1,000 to 20,000 cPs.

 The aerosol spray type hydrogel burn remedy according to the present invention is advantageous for initial burn treatment through rapid spray application.

Further, the aerosol spray type hydrogel burn-off therapeutic agent according to the present invention is characterized in that it provides an effect such as cooling necessary for the initial image treatment by improving the flowability and effectively maintaining the application state in the affected part after the application for a predetermined time.

Fig. 1 is a perspective view of the present invention in which an appropriate amount of an image treatment agent is placed in a circle in which a straight line is placed on top of a plane before tilting.
FIG. 2 shows an experimental example for measuring the length of the flow of viscosity according to the slope of Example 1 and Comparative Examples 1 and 2. FIG.
3 is a graph showing the results of Example 1 and Comparative Examples 1 and 2 at a tilt angle of 90 degrees.
4 is a graph showing the results of Example 1 and Comparative Examples 1 and 2 at a tilt angle of 45 degrees.
Fig. 5 shows an example of spraying an aerosol spray type hydrogel burn remedy of the present invention onto a burn site.
FIG. 6 is a graph showing the cooling temperature and the duration after the temperature measurement sensor is fixed to the skin, and Example 1 and Comparative Example 2 are sprayed onto the lesion.
FIG. 7 is a photograph of a cooling effect according to change of time after radiating the first and second comparative examples onto the affected part with a thermal imaging camera.

 In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted so as to avoid obscuring the subject matter of the present invention.

 The terms "about "," substantially ", etc. used to the extent that they are used herein are intended to be taken to mean an approximation of, or approximation to, the numerical values of manufacturing and material tolerances inherent in the meanings mentioned, Accurate or absolute numbers are used to help prevent unauthorized exploitation by unauthorized intruders of the referenced disclosure.

Hereinafter, the present invention will be described in more detail. The burn agent according to one embodiment of the present invention may include a base coolant, a cooling promoter, a coolant, and a thickener. In addition, the burn treatment agent may further comprise a pH adjusting agent, a fungicide or an antiseptic agent. Each of the above components may contain 27 to 94% by weight of a base coolant, 5 to 20% by weight of a cooling propellant, 0.1 to 50% by weight of a cooling sterilizer, and 0.5 to 3% by weight of a thickener. The constituent components of each of the burn therapeutic compositions of the present invention will be described in more detail as follows.

The base coolant refers to a solvent used to dissolve materials such as a cooling promoter, a cooling sterilizer, a thickener, a fungicide, and an antiseptic. Solvents are used for the purpose of dissolving various components and simultaneously achieving their performance, the function of determining the effective range of the components by adjusting the concentration of each component, and the basic capacity for sufficient injection. In addition, the solvent agent should be capable of dissolving the solute sufficiently. Water, which is a polar solvent, is most commonly used because of the characteristics of the liquid solute. Water is a good inorganic solvent (universal solvent) because it is a polar molecule with a dipole moment. Therefore, they are well mixed with polar substances and dissolve ionic substances such as sodium chloride (molecules with ionic bonds). Water has no flavor and aroma, it mixes well with other solutes and does not cause any chemical reaction. It is mainly used as a universal inorganic solvent.

Another use for water is cold water treatment by spraying the burn site by injection, and the clinical effect is on pain relief. The vasoconstriction is reduced at low temperatures and the vasoconstriction is maximal at 15 ° C. The peripheral neurotransmission decreases to 2.4 m / s per 1 ° C decrease, and the neurotransmission is completely blocked at 10 ~ 15 ° C. have. In addition, cold water treatment is expected to reduce secretion of inflammatory chemical messengers and reduce vasodilation and vascular permeability. Reduces tissue metabolic acidosis and preserves lymphatic channels to prevent lymphatic and protein stagnation. It is known that there is an effect of reducing edema. In the animal experiment with cold water treatment in the degradation phase, epidermal regeneration occurred about 10 days after burning, whereas epidermal necrosis, ulcer and fibrosis of the dermal layer were observed in the absence of cold water treatment. That is, cold water treatment can induce tissue necrosis and ultimately fibrosis, avoiding severe hypertrophic scars that may appear after deep burns. Water for this cooling effect is suitably from 27 to 94% by weight, preferably from 73 to 75% by weight.

The cooling propellant should have little toxicity as it touches the human body in order to act as a spraying agent and should have a low boiling point or melting point in order to be a propellant for forced injection. Among these materials, DME gas does not form a hydrogen bond, so it has a melting point of -141.5 ℃ and a boiling point of -24.9 ℃. These properties exist in the gaseous state at room temperature and are lower in flammability than LPG, so that the risk from fire is relatively low. Therefore, DME gas can be used as a spraying agent. However, if the content of the composition is within an appropriate range, and if it exceeds 20% by weight, the injection pressure becomes too strong, which may cause secondary damage due to strong pressure on the burned portion, In the range of less than% by weight, the effect as a propellant is low and there is a difficulty in spraying. Accordingly, 5 to 20% by weight, preferably 15 to 16% by weight, is suitable.

The cooling sterilizing agent may be ethanol as a non-limiting example. Ethanol has a good cooling effect and can function to prevent thermal damage of the burn area. Ethanol is useful for removing fire in burns while evaporating due to the effect of heat of vaporization.

 In addition, ethanol has the effect of coagulating proteins, and it also has disinfection and sterilizing action. It is expected that ethanol and water will evaporate after aerosol spraying to lower the temperature of the burn area, thereby reducing the secretion of inflammatory mediators more effectively and reducing vasodilation and vascular permeability than cold water treatment.

The range of ethanol is suitably from 0.1 to 50.0% by weight, preferably from 5.0 to 20.0% by weight. In case of mixing more than 20.0% by weight, cytotoxicity and skin irritation may cause the effect as a cooling disinfectant to be weaker than the maximum value. However, since the sample produced up to 50.0% by weight has excellent cooling effect upon spraying, it can be up to 50.0% by weight .

The viscosity of the composition is determined according to the amount of the thickener added so as to have a gel-type property. Viscosity increases with the addition of a thickener, which is generally a physical unit that indicates the degree of stickiness of the fluid. The change in viscosity after addition of the thickener can be judged by measuring in cPs units using a rotary viscometer.

 Though it is difficult to measure the viscosity strictly, it takes more time for the viscous fluid to compare the time when the same amount of liquid is taken down to the tube of the same thickness. At this time, it is possible to compare the viscosity by taking time with one liquid as a standard. Since viscosities usually decrease when the temperature rises, the temperature should be kept constant during the measurement.

It is a kind of thickener, which is a typical type of natural cellulose. It has a high viscosity and good film forming ability. It is used for cosmetics such as adhesion and increases volume and smoothness. Generally, it is chiseled. HEC (hydroxy ethyl cellulose) is mainly used, and 0.5 to 3% by weight, preferably 0.5 to 1.5% by weight is suitable. When the thickener is used in an amount of 0.5% by weight or less, the skin tends to flow down, and when the thickener is used in an amount of 3% by weight or more, problems may arise due to high viscosity.

In addition, as an example of non-limiting examples, there are alkaline swellable type and urethane combination type. Particularly, the urethane associative thickener has a wide choice of leveling properties and rigidity. In many cases, different types of thickeners are used together. Here, the term "plasticity" refers to a property that the shape is not deformed unless a certain amount of force is externally applied. Sealants or adhesives with a roughening property can flow through the vertical wall during the curing process and may not deform or deform its shape.

Table 3 shows the final viscosity change depending on the content of the thickener HEC in the burn agent and the content of ethanol as the coolant disinfectant incidentally. For example, in the case of 1.5 wt% of the thickener HEC, the viscosity is about 15,000 cPs (measured value is 14800) (Example 5) and the final viscosity can be controlled according to the ethanol content. When the viscosity of the thickener HEC is 2 wt% and ethanol is 10 wt% (Comparative Example 3), the viscosity is 15000 cPs. However, unlike Comparative Example 3, when the ethanol is added in an excess amount of 50 wt%, the viscosity is lowered to 10,000 cPs, and the viscosity can be controlled to some extent by the ethanol content. Therefore, it is possible to find the sprayable viscosity of the burn treatment agent by appropriate control of the ethanol content as well as the content of the thickener HEC.

 The pH adjusting agent may be used in an amount of 0.01 to 1 part by weight per 100 parts by weight of the burn agent to neutralize the acidity of the solution. the kind of the pH adjusting agent is not limited. Proper acidity maintenance can inhibit microbial growth and can also play an important role in preventing metal corrosion in containers. When the pH control agent was not added, it was acidic at pH 5.6, but neutralized at 0.02 part by weight. When the amount is 0.1 part by weight or more, it may be changed to basic. In addition, the other components, particularly tea tree oil and the like, are acidic and the amount of the pH adjuster may be varied depending on the content thereof. A maximum of 1 part by weight may be required. Table 4 shows the change in pH depending on the content of the pH adjusting agent. Therefore, the more the content of tea tree oil is, the more the pH adjuster content can be increased to neutralize.

Examples of the fungicide include tea tree oil, lavender, German Chamomile and Roman Camomile PHMB (polyhexamethylene biguanide), and silver antimicrobial agents.

The most suitable fungicide is tea tree oil, which is colorless or yellow and has good efficacy to remove various bacteria. It is said that about 100 ingredients contained in tea tree oil interact with each other to produce strong therapeutic and sterilizing properties. This oil penetrates deep into the skin and kills bacteria without harming healthy cells. Recent studies have shown that tea tree oil eradicates 58 bacteria, including Candida and Staphylococcus aureus. The constitution ratio is suitably 0.01 to 3 parts by weight, preferably 0.020 to 0.025 parts by weight, per 100 parts by weight of the image treatment agent. In the case of tea tree oil, there is little effect as a sedative for 0.01 part by weight or less, and cytotoxicity at a concentration of 0.03 parts by weight or more, but there is an example of using 3 parts by weight or more for increasing fungus power. 0.03 parts by weight does not cause cytotoxicity.

 As a non-limiting example, lavender is effective as an analgesic, sedative, antidepressant, antimicrobial, nerve stabilizer, and trauma treatment agent. German chamomile is effective in the treatment of antimicrobial, trauma, anti-inflammatory, sedative, eczema, psoriasis, acne, It is effective, and it is effective for the treatment of anti-inflammation, anti-sedation, atopy and the like.

Preservatives may be naturally occurring or chemically synthesized as a substance added to products such as food, pharmaceuticals, paints, biological samples, wood, etc. to prevent microbial growth or corruption due to unwanted chemical changes. Among them, methyl paraben (Methyl 4-hydroxybenzoate) is a widely used antiseptic ingredient widely used in cosmetics and personal care products. The longer the alkyl group is, the more excellent the antifungal effect is. The more excellent the antifungal effect, the higher the toxicity. Parabens are rapidly released without accumulation, but when parabens are hydrolyzed into benzoic acid, they can bind to lipids and concentrate in the body. In addition, non-limiting examples include propylparaben, benzyl alcohol, benzoic acid, sodium benzoate, potassium benzoate, sorbic acid, sodium sorbate, potassium sorbate and phenylethanol.

Hereinafter, an embodiment of the present invention will be described.

Example  One

50 g of a hydrogel stock solution obtained by mixing 100 g of water as a base coolant, 1 g of hydroxyethyl cellulose (HEC) as a thickener, 0.15 g of Methy paraban as a preservative, 5 g of ethanol as a cooling sterilizing agent and 1 g of fungicide as a fungicide And then 10 g of DME gas was further injected to prepare an aerosol spray type hydrogel burn agent.

Example  2

In Example 1, an aerosol spray type hydrogel burning therapeutic agent having 1.2 g of HEC and 10 g of ethanol was prepared.

Example  3

In Example 1, an aerosol spray type hydrogel burn treatment agent having 1.2g of HEC and 20g of ethanol was prepared.

Example  4

In Example 1, an aerosol spray type hydrogel burn treatment agent having 1.2 g of HEC and 15 g of ethanol was prepared.

Example  5

In Example 1, an aerosol soup type hydrogel burning therapeutic agent having 1.5 g of HEC and 10 g of ethanol was prepared.

Example  6

In Example 1, an aerosol spray type hydrogel burn treatment agent having 2.0 g of HEC and 50 g of ethanol was prepared.

Comparative Example  One

An aerosol moisturizer was prepared by mixing 46.5 g of water as a base coolant, 0.15 g of a carbomer as a thickener, 0.14 g of aminomethyl propanol as a cooling disinfectant, 0.7 g of Vitysviniferae leaf extract as a fungus sedative and 18.2 g of DME gas as a cooling propellant

Comparative Example  2

13 g of water as a base coolant, 0.51 g of PEG-10 Cetyl Ether as an emulsifier, 0.03 g of methylparaben as a preservative, and 0.02 g of tea tree oil as a fungicide were mixed to prepare a lotion-type burn agent.

Comparative Example  3

An aerosol burn remedy was prepared by mixing 100 g of water as a base coolant, 2 g of hydroxylethyl cellulose (HEC) as a thickener, 0.15 g of methy paraban as a preservative, 5 g of ethanol as a cooling disinfectant and 1 g of tea tree oil as a fungicide.

※ Test method

1. Place three fastening rings in a straight line on top of PET transparent film. The conditions of the retaining ring are 36 mm in inner diameter, 56 mm in outer diameter and 3 mm in thickness, and the temperature inside the laboratory is maintained at 22 ^° C. Thereafter, the same amount of the examples and the comparative examples are injected into the ring, and then the portion raised outside the ring is adjusted to a certain thickness by adjusting the height difference. (See Fig. 1)

2. After removing the ring, lift one side of the support of the transparent film to 90 degrees and 45 degrees, and measure the length of the flow of liquid for 10 seconds. (See Fig. 2)

90 degree slope
Time 10 seconds
Temperature 22 ⁰ C
1 time
Episode 2
3rd time
4 times
5 times
Average  Example 1 9 8 9 8.5 8 8.5  Comparative Example 1 15 16 15 14 15 15  Comparative Example 2 22 23 24 23 22 22.8

Unit: cm

45 degree inclination
Time 10 seconds
Temperature 22 ⁰ C
1 time
Episode 2
3rd time
4 times
5 times
Average  Example 1 5 4 4.5 5 3 4.3  Comparative Example 1 8 9 8.5 8 9 8.5  Comparative Example 2 14 13 13.5 14 14 13.7

Unit: cm

No.

water
(g)

HEC
(g)
methyl
paraben
(g)
Water + MP + HEC viscosity
(CPS)

EtOH
TTO
Change in viscosity after addition of EtOH + TTO
spray (cPs) possible Example 1 100 One 0.15 3700 5 One 3000 o Example 2 100 1.2 0.15 6400 10 One 5200 o Example 3 100 1.2 0.15 6400 20 One 4000 o Example 4 100 1.2 0.15 6400 15 One 4500 o Example 5 100 1.5 0.15 14800 10 One 11000 o Example 6 100 2 0.15 67500 50 One 10500 o Comparative Example 3 100 2 0.15 67500 5 One 35000 X

C One 2 3 4 5 6 7 pH adjusting agent C 0 0.01 0.02 0.05 0.1 0.15 One pH 7.4 5.672 7.04 7.32 7.54 7.855 8.11 8.766

As a result of the test, the liquid flowability of Example 1 was 1.76 times higher than that of Comparative Example 1 at a 90 degree slope, 2.68 times higher than that of Comparative Example 2, and 1.98 times higher than Comparative Example 1 at a slope of 45 degrees, There is a difference in liquid flow of the ship.

As a result, it can be seen that the therapeutic agent according to the present invention has a flowability that can be kept constant on the surface of the skin after spraying with the aerosol, and as a result, it is 2 to 3 ° C lower Temperature, indicating that it is useful for initial image processing.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the inventions. It will be clear to those who have knowledge of.

Claims (8)

27 to 94% by weight of a base coolant, 5 to 20% by weight of a cooling propellant, 0.1 to 50% by weight of a cooling sterilizing agent and 0.5 to 3% by weight of a thickener.
The aerosol spray type hydrogel burnable therapeutic agent according to claim 1, wherein 0.01 to 1 part by weight of a pH adjusting agent or 0.01 to 3 parts by weight of a fungicide is added to 100 parts by weight of the image processing agent.
The aerosol spray type hydrogel burnable therapeutic agent according to claim 1, wherein the bass coolant is water or purified water, the cooling propellant is DME gas, and the cooling sterilizing agent is ethanol.
The thickening agent according to claim 1, wherein the thickener is one or more selected from the group consisting of cellulose, gum, seaweed (alginic acid, carrageenan), protein (gelatin), alkali swellable type and urethane Wherein the aerosol spray type hydrogel is a therapeutic agent for burn injury.
The method according to claim 2, wherein the fungicide is at least one of tea tree oil, lavender, German Chamomile, Roman camomile, PHMB (polyhexamethylene biguanide) Wherein the aerosol spray type hydrogel burn treatment agent is an aerosol spray type hydrogel burn agent.
2. The aerosol spray type hydrogel burn treatment agent according to claim 1, wherein 0.08 to 0.13 part by weight of a preservative is added to 100 parts by weight of the image treatment agent.
7. The composition of claim 6, wherein the preservative comprises at least one of methylparaben, propylparaben, benzyl alcohol, benzoic acid, sodium benzoate, potassium benzoate, sorbic acid, sodium sorbate, potassium sorbate, and phenylethyl alcohol Wherein the aerosol spray type hydrogel is a therapeutic agent for burn injury.
2. The aerosol spray type hydrogel burn treatment agent according to claim 1, wherein the range of viscosity after spraying the therapeutic agent is in the range of 1,000 to 20,000 cPs.

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