CN115813949A - Application of fulvic acid in preparation of composition for preventing and treating skin burn caused by radiotherapy - Google Patents
Application of fulvic acid in preparation of composition for preventing and treating skin burn caused by radiotherapy Download PDFInfo
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- CN115813949A CN115813949A CN202211171935.7A CN202211171935A CN115813949A CN 115813949 A CN115813949 A CN 115813949A CN 202211171935 A CN202211171935 A CN 202211171935A CN 115813949 A CN115813949 A CN 115813949A
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- fulvic acid
- liquid dressing
- skin
- radiotherapy
- potassium sorbate
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- PUKLDDOGISCFCP-JSQCKWNTSA-N 21-Deoxycortisone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2=O PUKLDDOGISCFCP-JSQCKWNTSA-N 0.000 title claims abstract description 83
- FCYKAQOGGFGCMD-UHFFFAOYSA-N Fulvic acid Natural products O1C2=CC(O)=C(O)C(C(O)=O)=C2C(=O)C2=C1CC(C)(O)OC2 FCYKAQOGGFGCMD-UHFFFAOYSA-N 0.000 title claims abstract description 83
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Abstract
The invention discloses application of fulvic acid in manufacturing a medicine or liquid dressing for preventing skin burns during radiotherapy, wherein the liquid dressing contains fulvic acid and potassium sorbate, and a preparation method of the liquid dressing. The fulvic acid liquid dressing not only can not be absorbed through skin, but also can effectively prevent skin burn of tumor patients during radiotherapy.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to application of fulvic acid in preparation of a composition for preventing and treating skin burn caused by radiotherapy.
Background
Tumor patients typically require chemotherapy and radiation therapy to prevent tumor recurrence or metastasis. However, in the course of radiotherapy, if the radiation dose or the implementation method is not properly operated, the factors such as individual physique difference and the like easily cause physical burns on the local skin of radiotherapy, the damage depth is generally deep, and great pain is brought to patients. Generally, only a few of burn ointment can be applied to the skin after skin burns occur, and even if the burn ointment is healed, scars can be left.
Fulvic acid has wide sources, has been used as a traditional Chinese medicine component in China for decades, and can improve the immune function of organisms; promoting the growth of fiber cells; has obvious functions of removing necrosis, promoting granulation, resisting inflammation, etc.
Investigation has found that few products are available on the market which can be used to prevent skin burns during radiotherapy. Even with similarly acting products, the price is in the hundreds of yuan. Therefore, it is very necessary to research and develop a product containing fulvic acid as a main ingredient for preventing skin burn during radiotherapy. The product can fill the blank of domestic products for preventing skin burn during radiotherapy, and improve the life quality of tumor patients.
Disclosure of Invention
The invention aims to provide the application of fulvic acid in the preparation of a medicine or medical liquid dressing for preventing or treating skin burn caused by radiotherapy. The main using method comprises the following steps: the bottle body is shaken before radiotherapy, and after even shaking, the bottle body is sprayed on the surface of the skin for radiotherapy, and a layer of water film is formed on the surface of the skin, so that the effect of protecting the skin during radiotherapy is achieved.
In order to achieve the above object, the following embodiments are provided.
In one embodiment, the invention provides a use of fulvic acid in the manufacture of a medicament or medical fluid dressing for the prevention or treatment of skin burns resulting from radiation therapy.
According to the application of the invention, the fulvic acid is preferably mineral fulvic acid, and the liquid dressing is an external skin preparation.
In another embodiment, the liquid dressing for preventing and treating skin burn caused by radiotherapy comprises fulvic acid, a preservative and water.
The liquid dressing of the invention has the fulvic acid concentration of 0.5 mg/mL-10 mg/mL and the preservative concentration of 0.5 mg/mL-2 mg/mL.
In the liquid dressing of the present invention, the preservative is selected from sorbic acid or salts thereof and benzoic acid or salts thereof, preferably potassium sorbate, and the fulvic acid is mineral fulvic acid.
On the other hand, the invention also provides a preparation method of the medical liquid dressing, which comprises the following steps:
s1, adding fulvic acid into distilled water, and stirring to dissolve fulvic acid;
s2, adding potassium sorbate after the fulvic acid is completely dissolved, and stirring to dissolve the potassium sorbate;
and S3, adding sufficient distilled water after dissolving to ensure that the content of the fulvic acid is 0.5-10 mg/mL and the content of the potassium sorbate is 0.5-2.0 mg/mL.
The preparation method of the medical liquid dressing comprises the following steps:
1) Weighing a certain amount of fulvic acid powder and potassium sorbate by using a precision balance for later use;
2) Adding fulvic acid powder into a sterilized volumetric flask filled with a certain amount of distilled water, stirring at room temperature to dissolve, adding weighed potassium sorbate after fulvic acid is completely dissolved, and stirring at room temperature to dissolve;
3) And adding the residual distilled water after dissolving to ensure that the content of the fulvic acid in the liquid dressing is 0.5-10 mg/mL and the content of the potassium sorbate is 0.5-2 mg/mL.
The medical liquid dressing of the invention takes fulvic acid as a main component and is used for preventing skin burn during radioactive therapy. Especially for preventing skin burn of tumor patients during radiotherapy.
The liquid auxiliary materials comprise the following main components: 0.5 mg/mL-10 mg/mL fulvic acid, 0.5 mg/mL-2 mg/mL potassium sorbate and distilled water.
Compared with the existing product, the invention has the following beneficial effects:
the invention adopts fulvic acid as an active substance to prepare the skin liquid dressing product for preventing the skin from being burnt by radiotherapy, and the product can not generate transdermal absorption and pigmentation (pigmentation test) when being coated on the skin or sprayed on the surface of the skin and can also prevent (prevent) the skin from being burnt by radiotherapy radiation. In addition, the fulvic acid has wide raw material source and simple formula and process, not only can obviously reduce the cost of the radiotherapy protective agent, but also has obvious effect of preventing the skin from being burnt by radiotherapy.
(1) Transdermal absorption test
The liquid dressing of the present invention of batch No. 20200710 was evaluated for its degree of percutaneous absorption in vitro using Franz cell method, and the results of the study are shown in table 1 below.
(2) Pigmentation test
The liquid dressing of the invention of batch No. 20200710 was subjected to skin pigmentation test
Ordinary-grade Kunming mice were selected for pigmentation test of liquid dressing, and the following were indicated:
for normal skin of a mouse, the liquid dressing does not cause pigmentation;
for the skin of the affected part of the mouse injury, the liquid dressing can generate pigmentation within a short time, but can be recovered to a normal state after 5 days, the pigmentation disappears, and the inflammatory reaction of the affected part of the skin injury can not be generated.
Drawings
FIG. 1 is a scanning ultraviolet-visible spectrum of fulvic acid;
FIG. 2 is a graph of the four quadrant distribution of the depilatory skin on the back of the experimental mouse;
FIG. 3 is a photograph of experimental mice after completion of the administration on day 1;
FIG. 4 is a photograph of experimental mice after completion of the 5 th day administration;
FIG. 5 is a photograph showing experimental mice after completion of the administration on day 10;
FIG. 6 is a photograph showing the experimental mice after completion of the administration on day 15;
FIG. 7 is a graph showing the effect of 21 axillary radiation therapies in a blank test subject (breast cancer patient);
FIG. 8 is a graph of the effect of 15 post-operative radiation treatments on the chest of 1 of breast cancer subjects;
FIG. 9 is a graph showing the effect of 29 radiotherapy on the neck of 1 lung cancer subject.
Detailed Description
The present invention is described in detail below with reference to representative examples to assist in understanding the nature of the invention. While the present embodiment has been described with reference to the accompanying drawings, it is to be understood that the invention is not limited to the specific embodiments, but is intended to cover various changes, modifications and embodiments.
Example 1
Preparation of medical liquid dressing for preventing skin burn during radiotherapy
Comprises the following components: fulvic acid concentration is 0.5mg/mL, potassium sorbate concentration is 0.5mg/mL, and the balance is distilled water.
The preparation process comprises the following steps:
1) The mineral fulvic acid powder 50.00mg and the potassium sorbate 50.00mg are precisely weighed by a precision balance for later use.
2) Transferring the fulvic acid powder into a 100mL volumetric flask, adding a certain amount of distilled water, stirring and dissolving at room temperature, adding weighed potassium sorbate after the fulvic acid is completely dissolved, and stirring and dissolving at room temperature.
3) And (3) fixing the volume of the volumetric flask to 100mL by using distilled water, so that the content of fulvic acid in the liquid dressing is 0.5mg/mL, and the content of potassium sorbate is 0.5mg.
Example 2
Preparation of liquid dressing for preventing skin burn during radiotherapy
The formula is as follows: fulvic acid concentration is 0.5mg/mL, potassium sorbate concentration is 2.0mg/mL, and the balance is distilled water.
The preparation process comprises the following steps:
1) 50.00mg of fulvic acid and 200.00mg of potassium sorbate are precisely weighed by a precision balance for later use.
2) Transferring the fulvic acid powder into a 100mL volumetric flask, adding a certain amount of distilled water, stirring and dissolving at room temperature, adding weighed potassium sorbate after the fulvic acid is completely dissolved, and stirring and dissolving at room temperature.
3) And (5) fixing the volume of the volumetric flask to 100mL by using distilled water, so that the content of the fulvic acid in the liquid dressing is 0.5mg/mL and the content of the potassium sorbate is 2mg/mL.
Example 3
Preparation of liquid dressing for preventing skin burn during radiotherapy
The formula is as follows: the concentration of fulvic acid is 5mg/mL, the concentration of potassium sorbate is 0.5mg/mL, and the balance is distilled water.
The preparation method comprises the following steps:
1) Precisely weighing 500.00mg of fulvic acid and 50.00mg of potassium sorbate for later use by using a precision balance.
2) Transferring the fulvic acid powder into a 100mL volumetric flask, adding a certain amount of distilled water, stirring and dissolving at room temperature, adding weighed potassium sorbate after the fulvic acid is completely dissolved, and stirring and dissolving at room temperature.
3) And (5) fixing the volume of the volumetric flask to 100mL by using distilled water, so that the content of the fulvic acid in the liquid dressing is 5.0mg/mL and the content of the potassium sorbate is 0.5mg/mL.
Example 4
Preparation of liquid dressing for preventing skin burn during radiotherapy
The formula is as follows: the concentration of fulvic acid is 5.0mg/mL, the concentration of potassium sorbate is 2.0mg/mL, and the balance is distilled water.
The preparation method comprises the following steps:
1) Precisely weighing 500.00mg of fulvic acid and 200.00mg of potassium sorbate for later use by using a precision balance.
2) Transferring the fulvic acid powder into a 100mL volumetric flask, adding a certain amount of distilled water, stirring and dissolving at room temperature, adding weighed potassium sorbate after the fulvic acid is completely dissolved, and stirring and dissolving at room temperature.
3) And (5) making the volume of the volumetric flask to be 100mL by using distilled water, so that the content of the fulvic acid in the liquid dressing is 5.0mg/mL and the content of the potassium sorbate is 2mg/mL.
Example 5
Preparation of liquid dressing for preventing skin burn during radiotherapy
The formula is as follows: the concentration of fulvic acid is 10mg/mL, the concentration of potassium sorbate is 0.5mg/mL, and the balance is distilled water.
The preparation method comprises the following steps:
1) 1000.00mg of fulvic acid and 50.00mg of potassium sorbate are precisely weighed by a precision balance for later use.
2) Transferring the fulvic acid powder into a 100mL volumetric flask, adding a certain amount of distilled water, stirring and dissolving at room temperature, adding weighed potassium sorbate after the fulvic acid is completely dissolved, and stirring and dissolving at room temperature.
3) And (5) making the volume of the volumetric flask to be 100mL by using distilled water, so that the content of the fulvic acid in the liquid dressing is 10mg/mL and the content of the potassium sorbate is 0.5mg/mL.
Example 6
Preparation of liquid dressing for preventing skin burn during radiotherapy
The prescription has fulvic acid concentration of 10mg/mL, potassium sorbate concentration of 2.0mg/mL and the balance of distilled water.
The preparation method comprises the following steps:
1) 1000.00mg of fulvic acid and 200.00mg of potassium sorbate are precisely weighed by a precision balance for later use.
2) Transferring the fulvic acid powder into a 100mL volumetric flask, adding a certain amount of distilled water, stirring and dissolving at room temperature, adding weighed potassium sorbate after the fulvic acid is completely dissolved, and stirring and dissolving at room temperature.
3) And (5) making the volume of the volumetric flask to be 100mL by using distilled water, so that the content of the fulvic acid in the liquid dressing is 10mg/mL and the content of the potassium sorbate is 2mg/mL.
Example 7 transdermal experiments
External transdermal absorption assay for liquid dressings
Control 1 and control 2 were prepared as in example 1
And (3) replacing potassium sorbate with methyl paraben in the reference 1, and keeping the rest to obtain the reference 1.
And (4) replacing benzalkonium bromide with methyl paraben in the control 2, and keeping the balance to obtain the control 2.
The transdermal test is a comparison of the skin permeability of the liquid dressing of the invention (product as in example 1).
Laboratory apparatus
Instrument for experiment
Experimental methods
Establishment of method for measuring content of fulvic acid in fulvic acid liquid dressing
Determination of the ultraviolet absorption wavelength
After appropriate dilution of the liquid dressing, a uv-vis spectral scan was performed, which indicated a maximum absorption at 216 nm. The results are shown in FIG. 1.
Preparation of the Standard Curve
5.0mg of fulvic acid reference substance is precisely weighed, and is dissolved by distilled water to be constant volume to prepare standard stock solution with mass concentration of 50 mu g/ml. And sequentially diluting the standard stock solutions into standard solutions with mass concentrations of 0.25, 7.5, 10 and 15 mu g/ml respectively, and measuring the absorbance at a wavelength of 216 nm. And performing linear regression by taking the absorbance as an ordinate and the mass concentration of the fulvic acid as an abscissa. The results show a good linear relationship in the range of 0.5 to 15. Mu.g/ml. The regression standard curve equation is: a =0.042C +0.0048 2 ＝0.9997。
Preparation of mouse in vitro skin
Anesthetizing a mouse by intraperitoneal injection of 0.5% chloral hydrate, shaving abdominal hair, smearing depilatory cream for depilatory treatment, washing the depilatory part with normal saline, feeding for 24h, killing the mouse, peeling the unhaired abdominal skin, removing subcutaneous fat, washing with normal saline, sucking water by using filter paper, washing with phosphate buffer solution (PBS, pH 7.4) until the lotion is clear, and sucking water on the skin surface for later use.
In vitro transdermal absorption experiment
The transdermal absorption experiment was performed in a vertical Franz diffusion cell, which was placed in a drug transdermal diffusion tester and incubated in a constant temperature circulating water bath at 37 ℃. Fixing the excised skin of the mouse treated under the item 2.2 between the supply pool and the receiving pool, wherein the horny layer part faces the supply pool, and the effective permeation area is 3.5cm 2 . The volume of the receiving pool is 6.5mL by using physiological saline as a receiving medium. Precisely measuring 1.0mL of liquid dressing, and adding the liquid dressing to the surface of the horny layer of the in-vitro skin of the mouse in the supply poolAnd the opening at the upper section of the supply pool is sealed by a sealing film to prevent the evaporation of the liquid medicine and the leakage in the liquid taking process. Under the stirring speed of 300rpm, 1.0ml is sampled from the receiving pool at 15min, 1h, 2h, 4h, 8h and 24h respectively, and the equal amount of isothermal normal saline solution is supplemented after each sampling. And filtering the sucked receiving solution by a 0.22 mu m micropore filter membrane, performing sample injection measurement by adopting an ultraviolet spectrophotometry, and calculating the release amount of the medicament at different time points according to a regression equation of a standard curve. And the cumulative permeability per unit area was calculated as follows.
Cn in the formula is the mass concentration of the drug measured at the nth sampling point (μ g. ML) -1 ) (ii) a Ci is the mass concentration of the drug measured at the ith sampling point (μ g. ML) -1 ) (ii) a A is the effective transdermal penetration area of the diffusion cell; v is the receiving liquid volume; vi is the sample volume; cx is the concentration of drug in the feed tank (μ g. ML) -1 ) (ii) a Vx is the volume of drug in the feed reservoir.
After the transdermal experiment is finished, the skin is taken down from a diffusion cell, the rat skin with the effective area of the transdermal part is cut, the rat skin is washed for three times by deionized water, the rat skin is cut into pieces and placed in an EP tube, 2ml of deionized water is added for ultrasonic treatment for 60min, then the rat skin is centrifuged for 15min at 13000 rpm, and the supernatant is taken out and detected at 216 nm.
Results of the experiment
The results of the experiment show that 3 groups of mice in 24 hours, the liquid dressing (adjuvant: potassium sorbate) in the group 1, the control 1 (adjuvant: methyl paraben) in the group 2, and the control 2 (adjuvant: benzalkonium bromide) in the group 3 have the mean in vitro transdermal cumulative release rates of fulvic acid of 3.22% + -0.9%, 3.56% + -1.24% and 4.10% + -0.83% respectively, and the skin retentions of 1.24% + -0.27%, 1.29% + -0.21% and 1.37% + -0.15% respectively, as shown in tables 1, 2 and 3. The detailed experimental results are shown in table 1, table 2 and table 3.
Table 1 percentage of in vitro transdermal cumulative release of liquid dressing (potassium sorbate) (n = 3)
Table 2 percent in vitro transdermal cumulative release of control 1 (methylparaben) solution (n = 3)
Table 3 percent in vitro transdermal cumulative release of control 2 (benzalkonium bromide) solution (n = 3)
Conclusion of the experiment
Animal transdermal absorption experiments prove that the transdermal absorption of the liquid dressing (auxiliary material: potassium sorbate), the reference substance 1 (auxiliary material: methyl paraben) and the reference substance 2 (auxiliary material: benzalkonium bromide) is very little and can be ignored. However, in the aspect of comprehensive comparison of transdermal absorption rate and skin retention rate, potassium sorbate as a preservative is superior to methyl paraben and benzalkonium bromide.
Example 8 pigmentation test of fulvic acid liquid dressing on mouse skin surface
Experimental method
Treatment of mice
Taking 3 male common-grade Kunming mice, shaving the back hair of the experimental mice by using an electric hair cutter to expose the skin, then smearing depilatory cream, wiping off the redundant depilatory cream by using a soft cloth after acting for 10min, cleaning the skin at the depilatory position by using clean water, and feeding for 24h for later use.
Administration of drugs
The depilated skin on the back of the mouse was divided into four quadrants as shown in fig. 1, the upper left quadrant was used as a control area (No. 1), the lower left quadrant was subjected to skin laceration using a surgical blade, and then the liquid dressing solution of example 1 (No. 3) was coated with a cotton swab, the liquid dressing solution of example 1 (No. 2) was coated with a cotton swab in the upper right quadrant, and the liquid dressing solution of example 1 was coated with a cotton swab in the lower right quadrant, and wiped clean with a clean cotton swab after maintaining for 10min (No. 4). The administration was continued for 15 days, and the skin surface pigmentation of the mice was observed every day. Day 1 is shown in FIG. 2, day 5 is shown, day 10 is shown, and day 15 is shown.
From the above experimental results, it was found that, after the liquid dressing solution of the present invention was applied to normal skin, no matter the excess liquid dressing solution was wiped off after 10min administration or remained on the skin continuously, there was no pigmentation compared with the quadrant skin of the control area, and in the affected area with skin lesions, yellow pigment deposition on the wound was observed in the first four days, but there was no inflammatory reaction such as red swelling, ulceration and suppuration, and on the fifth day, the wound on the skin lesion was completely healed and recovered to the normal state.
Results of the experiment
For normal skin of a mouse, the liquid dressing solution of the invention does not cause pigmentation;
for the skin of the affected part of the mouse injury, the liquid dressing solution of the invention can generate pigmentation within a short time, but can be recovered to a normal state after 5 days, the pigmentation disappears, and the affected part of the skin injury can not generate inflammatory reaction.
EXAMPLE 9 clinical trial for prevention of radiation burn
Beginning at 7 months in 2022, shandong Ke Nuo De biomedical science and technology Co., ltd carries out a radiotherapy patient use test about 30 days per artificial period in a hospital, 10 tumor patients are selected to be grouped, wherein 1 patient with lung cancer, 2 patients with esophagus cancer and 7 patients with breast cancer need to collect the name, sex, age, height, weight, cancer species and occupational information of all the patients to be grouped before the first use and fill in a use recording card, a picture before the use is taken once, and then the patients enter the use period of the fulvic acid liquid dressing. Before the liquid dressing is used, the wound surface and the skin should be cleaned, and no foreign matter or moisture exists. When the face is used, the eyes are closed firstly; the bottle body is 15-20cm away from the skin, and the bottle body and the skin are uniformly sprayed back and forth at an angle of 45 degrees, and the gathered part is lightly tapped by fingers and abdomen to be uniformly scattered. Spray protection is carried out on irradiated and surrounding skin mucous membrane tissues for 1-2 times for about 30 days before radiotherapy, an irradiated part picture is taken every day, a later period is taken as a result judgment basis, the skin damage prevention degree is recorded on a recording table, and signature confirmation of a doctor is recorded.
Grading the acute radiation injury of the skin:
level 0 is essentially unchanged;
grade 1 follicular dark red spots/alopecia sicca/decreased sweating;
grade 2 tender or bright red spots, flaky moist alopecia/moderate edema;
the fused parts except the 3-grade skin folds are wet and peeled, and are sunken edema;
grade 4 ulcer/hemorrhage/necrosis.
10 tumor patients (containing 1 blank) were enrolled and subjected to a radiation therapy trial. Spraying the fulvic acid liquid dressing solution for 1-2 times before 15min before radiotherapy on the irradiated and surrounding skin mucosa tissues; after radiotherapy, immediately spraying liquid dressing solution for 1-2 times; spraying liquid dressing solution 3-5 times a day after the radiotherapy is finished. The types of cancers of 10 patients are different, most of the cancers have breast cancer, and other cancers such as lung cancer and the like exist; the middle-aged and the elderly are more; radiotherapy is performed after operation, and both sexes are available; time of radiation therapy, 35 times longest and 25 times shortest, all subjects using fulvic acid liquid dressing, skin rating after radiation therapy. The blank test patient is a breast cancer patient, the fulvic acid liquid dressing is not used for protection, and after radiotherapy, the skin burn degree reaches 4 grades, and is shown in figure 7. 9 subjects who used the fulvic acid liquid dressing of the present invention were slightly burned in the 0-1 grade change of the skin after radiotherapy; the macroscopic changes of the skin are limited as shown in fig. 8 and 9. FIG. 8 is a graph of the effect of 15 times of radiotherapy on the chest after 1 breast cancer operation, and FIG. 9 is a graph of the effect of 29 times of radiotherapy on the neck of 1 lung cancer patient. Compared with the control of 1 blank subject, the fulvic acid liquid dressing has obvious protection effect. The fulvic acid liquid dressing is proved to have very obvious effect of preventing skin burn when being used for radiotherapy of different cancer patients.
Claims (10)
1. Use of fulvic acid in preparation of medicine or medical liquid dressing for preventing and treating skin burn caused by radiotherapy is provided.
2. The use according to claim 1, wherein the fulvic acid is a mineral source fulvic acid.
3. The use according to claim 1, wherein the liquid dressing is an external skin preparation.
4. A liquid dressing for preventing and treating skin burn caused by radiotherapy comprises fulvic acid, antiseptic and water.
5. The liquid dressing of claim 4, wherein the concentration of fulvic acid is 0.5mg/mL to 10mg/mL and the concentration of preservative is 0.5mg/mL to 2mg/mL.
6. The liquid dressing of claim 4 or 5, said preservative being selected from sorbic acid or a salt thereof and benzoic acid or a salt thereof.
7. The liquid dressing of claim 4 or 5, said preservative being potassium sorbate.
8. The liquid dressing of claim 4 or 5, wherein said fulvic acid is a mineral source fulvic acid.
9. A method of manufacturing a liquid dressing according to any one of claims 4 to 8, comprising the steps of:
s1, adding fulvic acid into distilled water, and stirring to dissolve fulvic acid;
s2, adding potassium sorbate after the fulvic acid is completely dissolved, and stirring to dissolve the potassium sorbate;
and S3, adding sufficient distilled water after dissolving to ensure that the content of the fulvic acid is 0.5-10 mg/mL and the content of the potassium sorbate is 0.5-2.0 mg/mL.
10. The process according to claim 9, wherein the preservative is sorbic acid or a salt thereof and benzoic acid or a salt thereof.
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| CN202211171935.7A CN115813949A (en) | 2022-09-26 | 2022-09-26 | Application of fulvic acid in preparation of composition for preventing and treating skin burn caused by radiotherapy |
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| WO2007102813A1 (en) * | 2006-03-07 | 2007-09-13 | Advantage Marketing, Inc. | Compositions and methods for human use containing fulvic acid |
| CN102242152A (en) * | 2011-05-10 | 2011-11-16 | 华东理工大学 | Humic acid active component, preparation method and application thereof, and pharmaceutical composition containing same |
| US20120046361A1 (en) * | 2010-08-20 | 2012-02-23 | American Symbolic, Llc | Ethyl pyruvate compositions and methods |
| JP2016183130A (en) * | 2015-03-26 | 2016-10-20 | 株式会社コーセー | Agent for improving or preventing pigmentation |
| CN107398562A (en) * | 2017-07-14 | 2017-11-28 | 山西农业大学 | The preparation method of fulvic acid nano silver gel |
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| WO2007102813A1 (en) * | 2006-03-07 | 2007-09-13 | Advantage Marketing, Inc. | Compositions and methods for human use containing fulvic acid |
| US20120046361A1 (en) * | 2010-08-20 | 2012-02-23 | American Symbolic, Llc | Ethyl pyruvate compositions and methods |
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| JP2016183130A (en) * | 2015-03-26 | 2016-10-20 | 株式会社コーセー | Agent for improving or preventing pigmentation |
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