AU2021101843A4 - A composition for treating burn wounds - Google Patents

A composition for treating burn wounds Download PDF

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AU2021101843A4
AU2021101843A4 AU2021101843A AU2021101843A AU2021101843A4 AU 2021101843 A4 AU2021101843 A4 AU 2021101843A4 AU 2021101843 A AU2021101843 A AU 2021101843A AU 2021101843 A AU2021101843 A AU 2021101843A AU 2021101843 A4 AU2021101843 A4 AU 2021101843A4
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parts
acid
group
anpel
burn
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AU2021101843A
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Jingjing AN
Qian Chen
Guangyu Guan
Yinsheng Wu
Xie YAN
Dan Zhao
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    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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Abstract

The invention provides a composition for treating a burn wound, comprising a variety of ingredients, including a fatty acid 261 639mg, an organic substance 3.5-350mg, a carbohydrate 0.02 60mg, a vitamin 9-13pg, a microelement 3.04-5.5mg, an antibiotic 0.6-70mg, and an amino acid 105-335mg. The significant therapeutic effects of the invention include effectively promoting repair of a burn wound, anti-infection, inhibiting scar hyperplasia, no toxic side effect, convenient use, fast absorption, economical efficiency, etc. The invention provides patients with an efficient, economical, convenient and practical treatment for burn wounds, which greatly reduces the burden on patients, and effectively compensates for the various deficiencies of the current treatments for the non-healing burn wounds.

Description

A COMPOSITION FOR TREATING BURN WOUNDS
[0001] This application claims the benefit of priority to the Chinese patent application No.
CN202010591188.7, filed before China National Intellectual Property Administration on June 24,
2020, entitled "A mixture for treating burn wounds", all of which are incorporated herein by
reference.
TECHNICAL FIELD
[0002] The invention relates to the field of medical technology, in particular to a composition for
treating a burn wound.
BACKGROUND
[0003] A burn is an injury to a skin or other tissue or organ, which is mostly caused by high
temperature, radiation, electricity, friction, or exposure to chemicals. According to a recent
report from the World Health Organization, the burn is a global public health problem. Statistics
suggest that there are about 10 million burn patients, resulting in about 265,000 deaths
worldwide every year, most of which occur in low- or middle-income countries. In India, more
than 1 million people suffer from moderate or severe burns every year. A scar is one of the
sequelae of the burn with an incidence of 91.4%. The annual cost estimate for treating scars is at
least 4 billion dollars per year. The burn leads to heavy economic burdens to the state and the
society. A non-lethal burn, such as a non-healing burn wound, also cause huge mental trauma,
physical pain, and heavy economic burdens to the patients.
[0004] The non-healing burn wound frequently occurs over a long period of time after a burn
injury, carrying a risk of relapse and carcinogenesis. It remains a difficult problem to develop a
treatment for the non-healing burn wound suitable for clinic use, which is also important for the
research in the field of burns. A novel therapy for treating a non-healing burn wound is urgently
needed to solve the above problem.
SUMMARY
[0005] This application provides a composition for treating a burn wound.
[0006] The first aspect of the application provides a composition for treating a burn wound,
including the following ingredients in mass content: a fatty acid 261-639mg, an organic substance
3.5-350mg, a carbohydrate 0.02-60mg, a vitamin 9-13pg, a microelement 3.04-5.5mg, an
antibiotic 0.6-70mg, and an amino acid 105-335mg.
[0007] The second aspect of the application provides a composition for treating a burn wound,
which is recorded in parts byweight and includesthe following ingredients: 261-639 parts of fatty
acid, 3.5-350 parts of organic substance, 0.02-60 parts of carbohydrate, 0.009-0.013 parts of
vitamin E, 3.04-5.5 part of microelement, 0.6-70 parts of antibiotic, 105-335 parts of amino acid;
wherein,
the fatty acid is at least one selected from the group consisting of oleic acid, linoleic acid, linolenic
acid and palmitic acid;
the organic substance is at least one selected from the group consisting of ellagic acid,
hypaphorine, huperzine C, huperzine A, harmalol, abrine, berberine hydrochloride, 10-gingerol,
methyl gallate, spathulenol, 3-furylmethyl 1H-pyrrole-2-carboxylate, tanshinone, dihydrocapsaicin, potassium 7-hydroxy-1-naphthalenesulfonate, pilocarpine, adenosine,
firmanoic acid, glabrolide, liquidambaric lactone, schisandrolactone, dehydroepiandrosterone,
11(13)-dehydroivaxillin, 2-hydroxyeupatolide, 14,15beta-dihydroxyklaineanone, olaquindox,
oridonin, phorbol, harmine, maltol, hypoaconitine, 2-0-Rhamnosylicariside 11, theobromine,
theophylline, hordenine, ephedrine;
the carbohydrate is at least one selected from the group consisting of fructose and glucose;
the microelement is at least one selected from the group consisting of calcium, iron, zinc, copper,
and phosphorus; the antibiotic is at least one selected from the group consisting of mupirocin, neomycin, polymyxin B, gentamicin, amphotericin B and vancomycin; and the amino acid is at least one selected from the group consisting of glutamic acid, arginine, aspartic acid, serine, glycine, alanine, tyrosine, histidine, proline, cysteine, valine, isoleucine, leucine, phenylalanine, methionine, threonine, and lysine.
[0008] In some embodiments of the second aspect of the present application, the fatty acid also
include at least one selected from the group consisting of stearic acid, butyric acid, hexanoic acid,
octanoic acid, myristic acid, palmitoleic acid, heptadecanoic acid, eicosanoic acid, and cis-11
eicosenoic acid; wherein, in parts by weight, the total content of the oleic acid, linoleic acid,
palmitic acid and linolenic acid is not less than 250 parts.
[0009] In some embodiments of the second aspect of the present application, in parts by weight,
the fatty acid include: 20-50 parts of palmitic acid, 10-30 parts of stearic acid, 100-200 parts of
oleic acid, 100-300 parts of linoleic acid, 30-50 parts of linolenic acid, 0.1-1 parts of butyric acid,
0.1-1 parts of hexanoic acid, 0.1-1 parts of octanoic acid, 0.1-1 parts of myristic acid, 0.1-1 parts
of palmitoleic acid, 0.1-1 parts of heptadecanoic acid, 0.1-1 parts of eicosanoic acid and 0.3-2
parts of cis-11-eicosaenoic acid.
[0010] In some embodiments of the second aspect of the present application, in parts by weight,
the organic substance include: 0.1-10 parts of ellagic acid, 0.1-10 parts of hypaphorine, 0.1-10
parts of huperzine C, 0.1-10 parts of huperzine A, 0.1-10 parts of harmine, 0.1-10 parts of abrine,
0.1-10 parts of berberine hydrochloride, 0.1-10 parts of 10-gingerol, 0.1-10 parts of methyl
gallate, 0.1-10 parts of spathulenol, 0.1-10 parts of 3-furylmethyl 1H-pyrrole-2-carboxylate, 0.1
parts of tanshinone, 0.1-10 parts ofdihydrocapsaicin, 0.1-10 parts of potassium 7-hydroxy-1
naphthalenesulfonate, 0.1-10 parts of pilocarpine, 0.1-10 parts of adenosine, 0.1-10 parts of
firmanoic acid, 0.1-10 parts of glabrolide, 0.1-10 parts of liquidambaric lactone, 0.1-10 parts of
schisandrin, 0.1-10 parts ofdehydroepiandrosterone, 0.1-10 parts of 11(13)-dehydroivaxillin,
0.1-10 parts of 2-hydroxyzeranolide, 0.1-10 parts of 14,15beta-dihydroxyklaineanone, 0.1-10 parts of olaquindox, 0.1-10 parts of oridonin, 0.1-10 parts of phorbol, 0.1-10 parts of harmine,
0.1-10 parts of maltol, 0.1-10 parts of hypaconine, 0.1-10 parts of 2-0-rhamnosylicariside 1l, 0.1
parts of theobromine, 0.1-10 parts of theophylline, 0.1-10 parts of hordeine and 0.1-10 parts
of ephedrine.
[0011] In some embodiments of the second aspect of the present application, in parts by weight,
the carbohydrate include 0.01-30 parts of glucose and 0.01-30 parts of fructose.
[0012] In some embodiments of the second aspect of the present application, in parts by weight,
the microelement include: 0.5-1 parts of calcium, 0.01-0.1 parts of iron, 0.02-0.2 parts of zinc,
0.01-0.2 parts of copper, 2.5-4s part of phosphorus.
[0013] In some embodiments of the second aspect of the present application, in parts by weight,
the antibiotic include: 0.1-20 parts of mupirocin, 0.1-10 parts of neomycin, 0.1-10 parts of
polymyxin B, 0.1-10 parts of gentamicin, 0.1-10 parts of amphotericin B and 0.1-10 parts of
vancomycin.
[0014] In some embodiments of the second aspect of the present application, in parts by weight,
the amino acid include: 20-50 parts of glutamic acid, 20-40 parts of arginine, 10-30 parts of
aspartic acid, 5-20 parts of serine, 5-20 parts glycine, 5-20 parts of alanine, 5-20 parts of tyrosine,
1-10 parts of histidine, 1-10 parts of proline, 1-10 parts of cysteine , 5-10 parts of valine, 5-10
parts of isoleucine, 10-30 parts of leucine, 5-20 parts of phenylalanine, 1-5 parts of methionine,
2-15 parts of threonine and 4-15 parts of lysine.
[0015] The significant therapeutic effects of the composition for treating a burn wound provided
in the present invention include effectively promoting the repair of the non-healing burn wound,
anti-infection, inhibiting scar hyperplasia, no toxic side effect, convenient use, fast absorption,
economical efficiency, etc. The application provides the patients with an efficient, economical,
convenient and practical treatment for non-healing burn wounds, which greatly reduces the burden on patients, and effectively compensates for the various deficiencies of the current treatments for the non-healing burn wounds.
DESCRIPTION OF THE DRAWINGS
[0016] In order to explain more clearly the Examples of the present invention and the technical
solutions in the art, the drawings used in the Examples and the prior art are briefly described
below. It is obvious for those skilled in the art that the following drawings are only some
embodiments of the present invention, from which other drawings can be obtained without any
creative efforts.
[0017] Figure 1. Creation of porcine full-thickness burn wound models. (a) The burn-infliction
device. (b) A burn wound formation. (c) Histological analysis of the burn wound (x 40
magnification) 24 hours after burn injury. (d) This figure is a high magnification view of the area
indicated in 1c. (e) The eschar formation at 3 weeks after burn injury. (f) Clearance of necrotic
eschar at 3 weeks after burn injury and creation of porcine full-thickness burn wounds. (g) This
invention. (h) The wounded porcine covered with homemade elasticated jackets. Scale bar = 200
IIm.
[0018] Figure 2. Effects of this invention on porcine full-thickness burn wounds. Gross
appearance of wounds. Wounds were treated with this invention, rhEGF and saline for 1, 2, 3
and 4 weeks.
[0019] Figure 3. Quantification of residual wound area (burn wound area after treatment / burn
wound area at baseline x 100%) at week 1, 2, 3, and 4 post-treatment. Significance of the
differences between this invention and saline was set at *p < 0.05. Significance of the differences
between rhEGF and saline was set at #p < 0.05. Error bars indicate SEM.
[0020] Figure 4. Quantification of wound healing rate (burn wound area at baseline-burn wound
area after treatment / burn wound area at baseline x 100%) at week 1, 2, 3, and 4 post
treatment. Significance of the differences between this invention and saline was set at *p < 0.05.
Significance of the differences between rhEGF and saline was set at #p < 0.05. Error bars indicate
SEM.
[0021] Figure 5. Quantification of wound healing time at week 1, 2, 3, and 4 after treatment.
Significance of the differences between this invention and saline was set at *p < 0.05. Significance
of the differences between rhEGF and saline was set at #p < 0.05. Error bars indicate SEM.
[0022] Figure 6. Histologic and immunohistochemical staining analysis of the treated burn
wounds at day 28 after treatment with the composition of the present invention, rhEGF and
saline, with immunohistochemical staining of CK10, P63 in newly formed epidermis, and
Masson's Trichrome staining in newly formed dermis. Scale bar = 100lim.
[0023] Figure 7. Quantification of epidermal thickness at week 1, 2, 3, and 4 after treatment (the
proliferative and differentiated layers, im). Significance of the differences between this
invention and saline was set at *p < 0.05. Significance of the differences between rhEGF and
saline was set at #p < 0.05. Significance of the differences between this invention and rhEGF was
set at +p < 0.05. Error bars indicate SEM.
[0024] Figure 8. Quantification of P63 staining. Significance of the differences between this
invention and saline was set at *p < 0.05. Significance of the differences between rhEGF and
saline was set at #p < 0.05. Significance of the differences between this invention and rhEGF was
set at +p < 0.05. Error bars indicate SEM.
[0025] Figure 9. Quantification of CK10 staining. Significance of the differences between rhEGF
and saline was set at #p < 0.05. Significance of the differences between this invention and rhEGF
was set at +p < 0.05. Error bars indicate SEM.
[0026] Figure 10. Effects of this invention on human non-healing burn wounds. (a) Non-healing
wounds on back (child) over 1 month. (al) This invention applied on wounds. (a2) 4 days after
the treatment. (b) A non-healing wound on elbow over 1 month. (b1) This invention applied on
the wound. (b2) 1 week after the treatment. (b3) 2 weeks after the treatment. (c) Non-healing
wounds on back (adult) over 1 month. (c1) This invention applied on wounds. (c2) 3 days after
the treatment. (c3) 7 days after the treatment. (c4) 10 days after the treatment.
DESCRIPTION OF THE INVENTION
[0027] The invention is further described with reference to the following drawings and
embodiments, so that the objectives, the technical solutions, and the advantages of the present
invention are understood more clearly. It is obvious that the embodiments as described are only
some embodiments, rather than all embodiments of the present invention. Based on the
embodiments of the present invention, all other embodiments obtained by those skilled in the
art without creative effort shall fall within the protection scope of the present invention.
[0028] The first aspect of the application provides a composition for treating a burn wound,
including the following ingredients in mass content: a fatty acid 261-639mg, an organic substance
3.5-350mg, a carbohydrate 0.02-60mg, a vitamin 9-13pg, a microelement 3.04-5.5mg, an
antibiotic 0.6-70mg, and an amino acid 105-335mg.
[0029] It should be noted that, in the composition of the first aspect of the present application,
the mass content of each ingredient is based on the mass of 1 g composition. Similarly, in the
following preferred embodiments, the mass content of each ingredient is also based on the mass
of 1 g composition.
[0030] Preferably, the specific ingredients of the fatty acid are as follows: palmitic acid 20-50mg,
stearic acid 10-30mg, oleic acid 100-200mg, linoleic acid 100-300mg, linoleic acid 30-50mg,
butyric acid 0.1-1mg, hexanoic acid 0.1-1mg, octanoic acid 0.1-1mg, myristic acid 0.1-1mg,
palmitoleic acid 0.1-1mg, heptadecanoic acid 0.1-1mg, eicosanoic acid 0.1-1mg, and cis-11
eicosaenoic acid 0.3-2mg.
[0031] Preferably, the specific ingredients of the organic substance are as follows:
ellagic acid 0.1-10mg, hypaphorine 0.1-10mg, huperzine C 0.1-10mg, huperzine A 0.1-10mg,
harmalol 0.1-10mg, abrine 0.1-10mg, berberine hydrochloride 0.1-10mg, 10-gingerol 0.1-10mg,
methyl gallate 0.1-10mg, spathulenol 0.1-10mg, 3-furylmethyl 1H-pyrrole-2-carboxylate 0.1
mg, tanshinone 0.1-10mg, dihydrocapsaicin 0.1-10mg, potassium 7-hydroxy-1
naphthalenesulfonate 0.1-10mg, pilocarpine 0.1-10mg, adenosine 0.1-10mg, firmanoic acid 0.1
mg, glabrolide 0.1-10mg, liquidambaric lactone 0.1-10mg , schisanlactone 0.1-10mg,
dehydroepiandrosterone 0.1-10mg, 11(13) dehydroivaxillin 0.1-10mg, 2-hydroxy evanolactone
0.1-10mg, 14,15beta-dihydroxyklaineanone 0.1-10mg, olaquindox 0.1-10mg, oridonin 0.1-10mg,
phorbol 0.1-10mg, harmine 0.1-10mg, maltol 0.1-10mg, hypoconitine 0.1-10mg, 2-0
rhamnosylicariside II 0.1-10mg, theobromine 0.1-10mg, theophylline 0.1-10mg, hordeine 0.1
mg, and ephedrine 0.1-10mg.
[0032] Preferably, the specific ingredients of the carbohydrate are as follows:
Glucose 0.01-30mg, fructose 0.01-30mg.
[0033] Preferably, the specific ingredients of the vitamin are as follows:
a-Tocopherol 1.5-2.5pg, -Tocopherol 0.5-1.5pg, y-Tocopherol 4.5-5.5pg, 5-Tocopherol 2.5
3.5pg.
[0034] Preferably, the specific ingredients of the microelement are as follows:
Calcium 0.5-1mg, iron 0.01-0.1mg, zinc 0.02-0.2mg, copper 0.01-0.2mg and phosphorus 2.5-4mg.
wherein, calcium, iron, zinc, and copper are added to the composition in the form of soluble salts,
such as calcium gluconate, calcium hydrogen phosphate, calcium lactate, calcium chloride,
FeCl2-4H20, ferrous sulfate, ferrous gluconate, zinc gluconate, zinc sulfate, zinc acetate, copper
sulfate, copper gluconate, and the like, in which the phosphorus can be added in the form of
phosphate, such as sodium phosphate, disodium hydrogen phosphate, potassium dihydrogen
phosphate, etc., which are not limited in this application.
[0035] Preferably, the specific ingredients of the antibiotic are as follows:
mupirocin 0.1-20mg, neomycin 0.1-10mg, polymyxin B 0.1-10mg, gentamicin 0.1-10mg,
amphotericin B 0.1-10mg, and vancomycin 0.1-10mg.
[0036] Preferably, the specific ingredients of the amino acid are as follows:
glutamic acid 20-50mg, arginine 20-40mg, aspartic acid 10-30mg, serine 5-20mg, glycine 5-20mg,
alanine 5-20mg, tyrosine 5-20mg, histidine 1-10mg, proline 1-10mg, cysteine 1-10mg, valine 5
mg, isoleucine 5-10mg, leucine 10-30mg, phenylalanine 5-20mg, methionine 1-5mg, threonine
2-15mg, and lysine 4-15mg.
[0037] The second aspect of the application provides a composition for treating a burn wound,
which is recorded in parts by weight and includes the following ingredients: 261-639 parts of a
fatty acid, 3.5-350 parts of an organic substance, 0.02-60 parts of a carbohydrate, 0.009-0.013
parts of vitamins E, 3.04-5.5 parts of a microelement, 0.6-70 parts of an antibiotic, and 105-335
parts of an amino acid;
wherein,
the fatty acid is at least one selected from the group consisting of oleic acid, linoleic acid, linolenic
acid and palmitic acid;
the organic substance is at least one selected from the group consisting of ellagic acid,
hypaphorine, huperzine C, huperzine A, harmalol, abrine, berberine hydrochloride, 10-gingerol,
methyl gallate, spathulenol, 3-furylmethyl 1H-pyrrole-2-carboxylate, tanshinone, dihydrocapsaicin, potassium 7-hydroxy-1-naphthalenesulfonate, pilocarpine, adenosine,
firmanoic acid, glabrolide, liquidambaric lactone, schisandrolactone, dehydroepiandrosterone,
11(13) dehydroivaxillin, 2-hydroxyeupatolide, 14,15beta-dihydroxyklaineanone, olaquindox,
oridonin, phorbol, harmine, maltol, hypoaconitine, 2-0-rhamnosylicariside II, theobromine,
theophylline, hordeine and ephedrine;
the carbohydrate is at least one selected from the group consisting of fructose and glucose;
the microelement is at least one selected from the group consisting of calcium, iron, zinc, copper,
and phosphorus;
the antibiotic is at least one selected from the group consisting of mupirocin, neomycin,
polymyxin B, gentamicin, amphotericin B and vancomycin; and
the amino acid is at least one selected from the group consisting of glutamic acid, arginine,
aspartic acid, serine, glycine, alanine, tyrosine, histidine, proline, cysteine, valine, isoleucine,
leucine, phenylalanine, methionine, threonine, and lysine.
[0038] The inventors discovered in research that an excellent effect on treating burn wounds is
achieved by mixing various substances of specific contents in the composition of the present
application. Not limited to any theory, the inventor believes that this may be due to the
synergistic effect of the various ingredients.
[0039] In this application, the forms of calcium, iron, zinc, copper and phosphorus in the
microelement are not limited, as long as they can achieve the purpose of the present invention,
wherein calcium, iron, zinc and copper are added in the form of soluble salts, such as calcium
gluconate, calcium hydrogen phosphate, calcium lactate, calcium chloride, FeCl2-4H20, ferrous
sulfate, ferrous gluconate, zinc gluconate, zinc sulfate, zinc acetate, copper sulfate, copper
gluconate, and the like, in which the phosphorus can be added in the form of a phosphate, such
as sodium phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, etc.,
which is not limited in this application.
[0040] In this application, vitamin E includes a variety of different natural forms. This application
does not limit the specific form of vitamin E as long as the purpose of the present invention can
be achieved. For example, vitamin E can be at least one selected from the group consisting of a
tocopherol, p-tocopherol, y-tocopherol and 5-tocopherol.
[0041] Each ingredient in the composition of this application can be purchased from commercial
sources.
[0042] In some embodiments of the second aspect of the application, the fatty acid also includes
at least one selected from the group consisting of stearic acid, butyric acid, hexanoic acid,
octanoic acid, myristic acid, palmitoleic acid, heptadecanoic acid, eicosanoic acid, and cis-11
eicosenoic acid; wherein, in parts by weight, the total content of oleic acid, linoleic acid, linolenic
acid and palmitic acid is not less than 250 parts.
[0043] In some embodiments of the second aspect of the present application, in parts by weight,
the fatty acid includes: 20-50 parts of palmitic acid, 10-30 parts of stearic acid, 100-200 parts of
oleic acid, 100-300 parts of linoleic acid, 30-50 parts of linolenic acid, 0.1-1 parts of butyric acid,
0.1-1 parts of hexanoic acid, 0.1-1 parts of octanoic acid, 0.1-1s parts of myristic acid, 0.1-1 parts
of palmitoleic acid, 0.1-1 parts of heptadecanoic acid, 0.1-1 parts of eicosanic acid, and 0.3-2
parts of cis-11-eicosaenoic acid.
[0044] In some embodiments of the second aspect of the present application, in parts by weight,
the organic substance includes: 0.1-10 parts of ellagic acid, 0.1-10 parts of hypaphorine, 0.1-10
parts of huperzine C, 0.1-10 parts of huperzine A 0.1-10 parts of harmalol, 0.1-10 parts of abrine,
0.1-10 parts of berberine hydrochloride, 0.1-10 parts of 10-gingerol, 0.1-10 parts of methyl
gallate, 0.1-10 parts of spathulenol, 0.1-10 parts of 3-furylmethyl 1H-pyrrole-2-carboxylate, 0.1
parts of tanshinone, 0.1-10 parts ofdihydrocapsaicin, 0.1-10 parts of potassium 7-hydroxy-1
naphthalenesulfonate, 0.1-10 parts of pilocarpine, 0.1-10 parts of adenosine, 0.1-10 parts of
firmanoic acid, 0.1-10 parts of glabrolide, 0.1-10 parts of liquidambaric lactone, 0.1-10 parts of
schisanlactone, 0.1-10 parts ofdehydroepiandrosterone, 0.1-10 parts of 11(13)-dehydroivaxillin,
0.1-10 parts of 2-hydroxyeupatolide, 0.1-10 parts of 14,15beta-dihydroxyklaineanone, 0.1-10 parts of olaquindox, 0.1-10 parts of oridonin, 0.1-10 parts of phorbol, 0.1-10 parts of harmine,
0.1-10 parts of maltol, 0.1-10 parts of hypoaconitine, 0.1-10 parts of 2-0-rhamnosylicariside 1l,
0.1-10 parts of theobromine, 0.1-10 parts of theophylline, 0.1-10 parts of hordeine, and 0.1-10
parts of ephedrine.
[0045] In some embodiments of the second aspect of the present application, in parts by weight,
the carbohydrate includes 0.01-30 parts of glucose and 0.01-30 parts of fructose.
[0046] In some embodiments of the second aspect of the present application, in parts by weight,
the vitamin includes 0.0015-0.0025 parts ofa-tocopherol, 0.0005-0.0015 parts of p-tocopherol,
0.0045-0.0055 parts of y-tocopherol, and 0.0025-0.0035 parts of 5-tocopherol.
[0047] In some embodiments of the second aspect of the present application, in parts by weight,
the microelement includes: 0.5-1 parts of calcium, 0.01-0.1 parts of iron, 0.02-0.2 parts of zinc,
0.01-0.2 parts of copper, and 2.5-4 parts of phosphorus.
[0048] In some embodiments of the second aspect of the present application, in parts by weight,
the antibiotic includes: 0.1-20 parts of mupirocin, 0.1-10 parts of neomycin, 0.1-10 parts of
polymyxin B, 0.1-10 parts of macromycin, 0.1-10 parts of amphotericin B, and 0.1-10 parts of
vancomycin.
[0049] In some embodiments of the second aspect of the present application, in parts by weight,
the amino acid includes: 20-50 parts of glutamic acid, 20-40 parts of arginine, 10-30 parts of
aspartic acid, 5-20 parts of serine, 5-20 parts of glycine, 5-20 parts of alanine, 5-20 parts of
tyrosine, 1-10 parts of histidine, 1-10 parts of proline, 1-10 parts of cysteine, 5-10 parts of valine,
-10 parts of isoleucine, 10-30 parts of leucine, 5-20 parts of phenylalanine, 1-5 parts of
methionine, 2-15 parts of threonine, and 4-15 parts of lysine.
[0050] As for the compound in the present application, each type of ingredient can be separately
mixed first, and then the mixed ingredients can be subjected to a second mix. For example, first
mix the various ingredients of the fatty acid, mix the various ingredients of the organic substances,
mix the various ingredients of the carbohydrate, mix the various ingredients of the vitamin, mix
the various ingredients of the microelement, mix the various ingredients of the antibiotic, mix
the various ingredients of amino acids, and then introduce these mixed ingredients into one container for a second mix. There is no chemical reaction between the ingredients once the composition is prepared, which only includes a physical mixing. Therefore, the preparation method can be obtained by referring to the physical mixing methods in the prior art, which is not limited in this application.
[0051] The present application will be specifically explained based on Examples as follows,
although not limited thereto.
[0052] Example 1
Mix the following ingredients to obtain the composition of this application:
Linoleic acid 2700mg, ellagic acid 50mg, pilocarpine 50mg, methyl gallate 50mg, glucose 5mg,
vitamin E 100ig, calcium lactate 218mg, mupirocin 100mg, glutamic acid 500mg, arginine 400mg,
and tyrosine 200mg.
[0053] Example 2
Mix the following ingredients to obtain the composition of this application:
Oleic acid 2000mg, linoleic acid 2000mg, hypaphorine 50mg, liquidambaric lactone 50mg,
oridonin 50mg, maltol 50mg, glucose 100mg, fructose 100mg, vitamin E 200pg, calcium lactate
109mg, potassium dihydrogen phosphate 136mg, vancomycin 100mg, neomycin 100mg, serine
500mg, aspartic acid 400mg, methionine 200mg, and alanine 400mg.
[0054] Example 3
Mix the following ingredients to obtain the composition of this application:
Palmitic acid 340mg, stearic acid 130mg, oleic acid 1080mg, linoleic acid 2410mg, linolenic acid
360mg, butyric acid 1.3mg, hexanoic acid 5mg, octanoic acid 5mg, myristic acid 9mg, palmitoleic
acid 3mg, heptadecanoic acid 2mg, eicosanoic acid 4mg, cis-11-eicosaenoic acid 12mg, each of
ellagic acid, hypaphorine, huperzine C, huperzine A, harmalol, abrine, berberine hydrochloride,
-Gingerol, methyl gallate, spathulenol, 3-furylmethyl 1H-pyrrole-2-carboxylate, tanshinone,
dihydrocapsaicin, potassium 7-Hydroxy-1-naphthalenesulfonate, pilocarpine, adenosine, firmanoic acid, glabrolide, liquidambaric lactone, schisanlactone, dehydroepiandrosterone,
11(13)-dehydroivaxillin, 2-hydroxy edenoid, 14,15beta-dihydroxyklaineanone, olaquindox,
oridonin, phorbol, harmine, maltol, hypoaconitine, 2-0-Rhamnosylicariside 11, theobromine,
theophylline, hordeine, and ephedrine 2mg, glucose 5mg, fructose 5mg, a-tocopherol 18pg, p
tocopherol 8pg, y-tocopherol 55pg, 5-tocopherol 35pg, calcium lactate 27mg, ferrous gluconate
2.6mg, zinc gluconate 3.4mg, copper gluconate 0.7mg, disodium phosphate 128mg, mupirocin
2mg, neomycin 100mg, polymyxin B 5mg, gentamicin 5mg, amphotericin B 5mg, vancomycin
mg, glutamic acid 400mg, arginine 280mg, aspartic acid 150mg, serine 100mg, glycine 100mg,
alanine 90mg, tyrosine 60mg, histidine 40mg, proline 60mg, cysteine 20mg, valine 80mg,
isoleucine 70mg, leucine 130mg, phenylalanine 90mg, methionine 20mg, threonine 65mg, and
lysine 50mg.
[0055] The sources of the ingredients in each of the above examples are listed in Table 1.
TABLE 1
The Sources of the Components
Ingredient CAS No. Company SPEC Product ID Palmitic acid 57-10-3 Anpel 5g CFEQ-4-510012-0005 Stearic acid 57-11-4 Anpel 5g CFEQ-4-530173-0005 Oleic acid 112-80-1 Anpel 100mg CFEQ-4-531190-0001 Linoleic acid 60-33-3 Anpel 1g CFEQ-4-533134-0001 Linolenic acid 463-40-1 Anpel 5ml CFEQ-4-533060-0005 Butyric acid 107-92-6 Anpel 5ml CFEQ-4-420764-0005 Fatty Hexanoic acid 142-62-1 Anpel 100ml CFEQ-4-470115-0100 acids Octanoic acid 124-07-2 Anpel 5ml CFEQ-4-531037-0005 Myristic acid 544-63-8 Anpel 5g CFEQ-4-490486-0005 Palmitoleic acid 373-49-9 Anpel 100mg CFAD-P9417 Heptadecanoic acid 506-12-7 Anpel 25g CFLD-H122278 Eicosanoic acid 506-30-9 Anpel 100mg CDFT-016-05721
cis-11-Eicosenoic acid 5561-99-9 Anpel / CFAD-E3635
Ellagic acid 476-66-4 Anpel 20mg CDAA-280576 Organ1Hypaphorine 487-58-1 Anpel 5mg CDHJ-ST1700010 ssHuperzine A 102518-79-6 Anpel 20mg CDAA-280495 substa nces Huperzine C 163089-71-2 Chemfaces 20mg CFN90345 Harmalol 525-57-5 Anpel 1mg CDFX-PHY89701
CDFV-ALX-106-040 Abrine 21339-55-9 Anpel 50mg M050 Berberine hydrochloride 633-65-8 Anpel 20mg CDAA-280255 -Gingerol 23513-15-7 Anpel 20mg CDAA-281614 Methyl gallate 99-24-1 Anpel 20mg CDAA-280761 Spathulenol 6750-60-3 Anpel 5mg CDBO-B30013 3-furylmethyl1H-pyrrole- 119767-00-9 Anpel 5mg CDHJ-ST8278010 2-carboxylate Tanshinone 568-73-0 Anpel 20mg CDAA-281232 Dihydrocapsaicin 19408-84-5 Anpel 20mg CDBD-CCPE900179 Potassium 7-Hydroxy-1- 30252-40-5 Anpel 20mg CDAA-281330 naphthalenesulfonate Pilocarpine 92-13-7 Aladdin 300mg 1538505 Adenosine 58-61-7 Anpel 1Og CFLD-A108808 Chengdu Firmanoic acid 107584-83-8 Biopurify Co., 5g MOL-PMIOX-849813 Ltd. Glabrolide 10401-33-9 Anpel 5mg CDHJ-ST5514010 Liquidambaric lactone 185051-75-6 Anpel 5mg CDHJ-ST1600010
Schisanlactone 136040-43-2 Baoji Earay 10mg YRS1574 Co., Ltd 1m R17 Dehydroepiandrosterone 53-43-0 Anpel 20mg CDBO-DT0053
Shanghai 11(13)-Dehydroivaxillin 87441-73-4 Yuanmu Co., / YM-0019 Ltd. 2-hydroxyeupatolide 72229-33-5 Anpel 10mg CDHI-E-0192
14,15beta- 137359-82-1 Anpel 20mg CDHJ-ST8253010 Dihydroxyklaineanone
Olaquindox 23696-28-8 Anpel 100mg CDBD-CCAD300339 Oridonin 28957-04-2 Anpel 50mg CFLD-0111382 Phorbol 17673-25-5 Anpel 20mg CDHJ-ST243901 Harmine 442-51-3 Anpel 1g CDFT-351-00361 Maltol 118-71-8 Anpel 100mg CDBD-CCPD101352 Chengdu Hypaconine 63238-68-6 Biopurify Co., 5mg BP3199 Ltd.
2-0-Rhamnosylicariside 11 135293-13-9 Anpel 5mg CDHJ-ST1855010
Theobromine 83-67-0 Anpel 20mg CDAA-280904 Theophylline 58-55-9 Anpel 5g CFEQ-4-401712-0005
Hordenine 539-15-1 Anpel 20mg CDAA-281238 Ephedrine 299-42-3 Anpel 25g CFGF-158940250 Carbo Glucose 50-99-7 Anpel 100g CFEQ-4-532058-0005 hydratD-Fructose 57-48-7 Anpel 5g CFEQ-4-460070-0005 es a-Tocopherol 10191-41-0 Anpel 5g CFAE-258024 Vitami P-Tocopherol 16698-35-4 Anpel 25mg CDDM-T526130 ns y-Tocopherol 54-28-4 Anpel 25mg CFAD-T1782 5-Tocopherol 119-13-1 Anpel 100mg CDAA-120001 Calcium 814-80-2 Anpel 50g CFBO-2009 Micro Iron 299-29-6 Anpel 500g CDFT-096-00785 eleme Zinc 4468-02-4 Anpel 5g CFEQ-4-540015-0005 nts Copper 527-09-3 Anpel 100g CFEQ-4-441860-0100 Phosphorus 7558-79-4 Anpel 50mg CDCT-C13000000 Mupirocin 12650-69-0 Anpel 100mg CDGO-130568 Neomycin 1405-10-3 Anpel 200mg CDGO-130309 Antibi Polymyxin B 1404-26-8 Anpel 2.25mg CMLQ-P-36H otics Gentamycin 1403-66-3 Anpel 0.1g CMLQ-P-04 Amphotericin B 1397-89-3 Anpel 250mg CDFT-015-13361 Vancomycin 1404-93-9 Anpel 0.2g CMLQ-P08 Glutamic acid 56-86-0 Anpel 200mg CDAA-270005 Arginine 74-79-3 Anpel 200mg CDAA-270002 Aspartic acid 56-84-8 Anpel 200mg CDAA-270003 Serine 56-45-1 Anpel 200mg CDAA-270014 Glycine 56-40-6 Anpel 100g CFEQ-4-532109-0100 Alanine 56-41-7 Anpel 200mg CDAA-270018 Tyrosine 60-18-4 Anpel 200mg CDAA-270016 Histidine 71-00-1 Anpel 200mg CDAA-270007 Acino Proline 147-85-3 Anpel 200mg CDAA-270013 acids Cysteine 52-90-4 Anpel 200mg CDAA-270022 Valine 72-18-4 Anpel 200mg CDAA-270017 Isoleucine 73-32-5 Anpel 200mg CDAA-270008 Leucine 61-90-5 Anpel 200mg CDAA-270009 Phenylalanine 63-91-2 Anpel 200mg CDAA-270012 Methionine 63-68-3 Anpel 1Og CFLD-M101130 Threonine 72-19-5 Anpel 200mg CDAA-270015 I_ Lysine 56-87-1 Anpel 200mg CDAA-270010
[0056] Test example 1: Animal full-thickness burn healing experiment
[0057] Ethics: The Ethical Approval of this experiment has been acquired. Animals used in the
experiment were treated humanely. The experiment process complies with the relevant
regulations of Animal Health and Protection Act and the Code of Practice for Animal Care and
Use for Scientific Purposes.
[0058] Experimental animals: Three female Guangxi Bama mini-pigs are 19-21 kilograms
(provided by Tianjin Bainong Laboratory Animal Breeding Technology Co., Ltd., Tianjin, China).
Animals were housed in isolated steel cages (80 x 100 x 110 cm3) at 25°C under natural lighting
in the Experimental Animal Center, after thoroughly disinfecting the breeding room and the
cages for animals with disinfectants and ultraviolet lamps. Non-experimental personnel are
strictly prohibited from entering the breeding room during the experiment. Animals were fed
with standard pig chow twice daily, 150 grams at a time, and had access to water ad libitum
(water is of the clean standard for tap water). The breeding room and cage are disinfected
regularlyon a weekly basis, and thefeed tankand the watersinkare cleaned before each feeding.
[0059] Creation of porcine full-thickness burn wound models: The miniature pig was raised
conventionally, fasted for 12h, laid on one side, and injected with sumianxin injection into the
hip muscle. Once anesthetized, the miniature pig was transferred to an operating table and a
ventilation tube was placed in the mouth. After disinfection of the back of the ear, an indwelling
needle of the auricle vein was placed for adequate analgesia and sedation. The surgical area on
the back was prepared, disinfected with iodophor, on which a sterile sheet was spread, and an
expected site of a burn was marked. The aluminum block mold (the net weight of the aluminum
block mold is 265g, and the load is 1kg) was heated to 96°C for 10 minutes, and was in close
contact with the skin for 45 seconds. Each pig had 9 wounds. The operation on the back of the 3
mini pigs is consistent. After the operation, the wounds were disinfected with iodophor, on which
cotton pads dressing and elastic sleeves were applied. Antibiotics were injected intravenously to
prevent infection, and 2ml of the awakening agent Lu Xingning was injected intravenously. The
pigs were then transferred to the cages. One hour after waking up, the pigs were fed and given
oral rehydration saline. Activities and signs of the pigs were closely observed. After the burn injury, local debridement and different treatments were performed on the wounds. Three weeks after injury, the wounds were covered by necrotic eschar, without exudate and dissolution reaction. Excisional debridement down to the fat layer was performed. Wounds were then dressed and covered with elasticated jackets to prevent animal-initiated damage. Preemptive antibiotics and analeptic Lu Xingning were administered i.v., then the animals were transferred to individual cages, and monitored closely for adverse outcomes during their post-procedure recovery. Post-surgical pain was managed with oral analgesia.
[0060] In order to verify the therapeutic effect of the composition of this application on burn
wounds, the composition of Example 3 of this application, recombinant human epidermal growth
factor rhEGF (50001U/mL, 15mL, Shenzhen Watsin Genetech Ltd.) and physiological saline were
used respectively to treat the full-thickness burn wounds of the pigs. The wounds were
photographed and measured at day 7, 14, 21, 28 after different treatments. The wound healing
with time is shown in FIG. 2. It can be seen from FIG. 2 that the new granulation tissue of the
wound is fresh and rosy without exudation. The skin in the healing part of the wound forms a
scar with darker color and slightly harder texture than normal skin, which is slightly higher than
the surrounding normal skin, and the wound healing part has no hair growth. There are no
reactions, such as redness, blisters, or ulceration around the wound, and no deterioration, such
as further enlargement or necrosis. It can be seen from the local conditions of the wound at day
28 after treatment that the area of scar formed after the treatment with the present invention
is smaller and lighter in color than that of the rhEGF group. The wounds in both groups treated
with the present invention and the rhEGF heal faster than those of the saline group.
[0061] The changes of the residual wound area and the wound healing rate are shown in FIG. 3
and FIG. 4, respectively, wherein the residual wound area (%) = (burn wound area aftertreatment
/ burn wound area at baseline) x 100%, and the wound healing rate (%) = (burn wound area at
baseline - burn wound area after treatment) x 100%. It can be seen from FIG. 3 that the present
invention obviously reduced wound area at day 7, 14, 21, 28 after treatment, compared to the
saline group (*p<0.05, compared with the physiological saline group). The positive control rhEGF
obviously reduced wound area at day 28 after treatment, compared to the saline group (#p<0.05, compared with the physiological saline group). These data suggests that the present invention has significantly reduced wound area. FIG. 4 shows that the present invention obviously improved wound healing rate at day 7, 14, 21, 28 after treatment, compared to the saline group
(*p<0.05, compared with the physiological saline group). The positive control rhEGF obviously
improved the wound healing rate at day 7, 14, 21 after treatment, compared with saline group
(#p<0.05, compared with the physiological saline group). There were no significant differences
between the present invention and rhEGF (p = 0.946). These data suggests that the present
invention has improved healing rate of burn wounds.
[0062] Wound healing time is defined as the time taken to reach complete epithelialization.
Individual burn wounds were clinically assessed and photographed at day 7, 14, 21, 28 post
treatment. As shown in Table 2 and FIG. 5, the time required to achieve complete wound healing
was 18.44 ±3.09 days in the present invention, 23.56 ±4.85 days in the rhEGF group, and 32.56
±5.36 days in the saline group (Fig. 5 & Table 2). These data indicated that the present invention
significantly shortens the wound healing time. No difference is observed between the wounds
treated with the present invention of interest and those treated with rhEGF (p = 0.063), indicating
that the effect and the wound healing time of the composition of the present application on
wounds is equivalent to those of rhEGF. In FIG. 5, * represents the statistical significance of
between this invention and the negative control group; # represents the statistical significance
between rhEGF and the negative control group.
TABLE 2. Comparison of Wound Healing Time
Number of Wound healing time Group F P cases (days, X +/- S)
This invention 9 18.44 3.091,3
rhEGF 9 23.56 ±4.852 22.288 < 0.001
Saline 9 32.56 ±5.36
'P < 0.01 This invention versus Saline group. 2p < 0.01 rhEGF versus Saline group. 3 p > 0.05 This
invention versus rhEGF.
[0063] Wound healing assessment (histologic and immunohistochemical analysis): An
immunohistochemistry analysis was performed to identify the localization and expression of
specific molecular markers of keratinocytes in the healed epidermis. The results of
immunohistochemistry and Masson staining at 4 weeks after treatment on wounds are shown in
FIG. 6.
[0064] It can be seen from FIG. 6 that the nuclear transcription factor P63 was mainly expressed
in undifferentiated proliferating keratinocytes located in the basal layer. CK 10 was mainly
expressed in mature differentiating keratinocytes. The expression of P63 and CK10 protein
indicate the proliferation and differentiation of keratinocytes during epithelialization and repair
of wounds. The higher the expression of P63 and CK10 protein, the faster the cells proliferate
and differentiate. In the late stage of wound repair, fibroblasts secrete more collagen fibers, and
a large number of collagen fibers increase and are densely arranged. Masson staining is used to
mark the subcutaneous collagen fibers as green. The structure of each layer of the epidermis
treated with the present invention is clear. The proliferative layer and the differentiated layer
can be clearly identified by immunohistochemical staining.
[0065] Integrated optical density (IOD) values analysis of immunohistological images of P63 and
CK10 are performed by Image-Pro Plus 6.0, as shown in Table 3 and FIGs. 8 to 9. The expression
of P63 in the healed epidermis treated with the present invention was significantly weaker than
that of the rhEGF group, but stronger than that of the saline group (p < 0.05). (In FIG. 8, *
represents the statistical significance between this invention and the saline group; # represents
the statistical significance between the rhEGF group and the saline group; + represents the
statistical significance between this invention and the rhEGF group.) The expression of CK10
protein treated with the present invention was weaker than that of the rhEGF group. (In FIG. 9, * represents the statistical significance between this invention and the saline group; # represents
the statistical significance between the rhEGF group and the saline group; + represents the
statistical significance between this invention and the rhEGF group.) It should be noted that
overexpression of P63 and CK10 protein means cell overproliferation and overdifferentiation,
resulting in excessively thick proliferation and differentiation layers in the epidermis, and thus scars are easily formed. The expression of P63 and CK10 protein in the present invention is weaker than that of the rhEGF group, so that the scars after wound healing are less likely to be formed.
TABLE 3
Integrated Optical Density (IOD) of Immunohistochemistry
IOD(P63) IOD(CK10) Group S F P _ F P ( X +/-S) ( X+/-S)
This 15311.09 218625.08±
invention 10443.271,3 81454.753
21929.27± 395254.15± rhEGF 11.292 <0.05 39.312 <0.05 17138.002 99751.142
8216.11 245901.76± Saline 6860.73 90848.92
'P<0.05, This invention versus Saline group; 2P<0.05, rEGF versus Saline group; 3P<0.05, This
invention versus rEGF group.
[0066] The epidermis partitions into two layers: a proliferative layer and a differentiated layer.
The thickness of each of these two layers treated with the present invention was significantly
thinner than that of the healed skin tissue treated with rhEGF, as shown in Table 4 and FIG. 7 (*
represents the statistical significance between this invention and the saline group; # represents
the statistical significance between the rhEGF group and the saline group; + represents the
statistical significance between this invention and the rhEGF group). The results indicate that the
use of the present invention to treat wounds will produce smaller scars than rhEGF treatment.
TABLE 4
Comparison of the Thickness Between Proliferative Layer and Differentiated Layer
Thickness of Thickness of
proliferative differentiated Group F P F P layer layer
(X +/- S) (pm) (X +/- S) (pm) This 28.00 10.16", 132.32± 50.493 invention 40.224 < 0.05 44.032 < 0.05 rhEGF 35.92 ±10.392 246.20 ±76.472
Saline 17.37 ±4.63 137.24 ±42.04
'P<0.05, This invention versus Saline group; 2P<0.05, rhEGF versus Saline group; 3 P<0.05, This
invention versus rhEGF.
[0067] The above results from porcine study indicate that the present invention has a significant
healing effect on wounds, especially non-healing wounds (full-thickness burn wounds). The
wound healing rate and healing time of the present invention are equivalent to those of the
rhEGF group, indicating that the present invention has a good effect of treating burn wounds.
More importantly, compared with the rhEGF group, the epidermal proliferative layer and the
differentiated layer treated with the present invention are thinner, which means that the
probability of scarring is less. From this perspective, the present invention has a better
therapeutic effect than rhEGF. Moreover, the present invention has a lower cost than rhEGF,
which is beneficial to clinical application and popularization, and reduces the economic burden
of patients.
[0068] Test Example 2. Verification of wound healing in patients with burn wounds
[0069] Clinically, non-healing wounds refer to wounds that do not heal or show no healing
tendency after 1 month of treatment. In this application, medical records of 430 patients,
including 368 male and 60 female, aged from 1 to 70 years old, with a clinical diagnosis of at least
one non-healing burn wound were collected. The burn injury includes 150 cases of hydrothermal
burns, 167 cases of flame burns, 84 cases of electric burns, and 29 cases of chemical burns. The
430 patients had an area of a third-degree burn of 0.2%-53.5% TBSA (total body surface area), and an area of a non-healing burn wound formed thereafter of 0.1%-7% TBSA. The non-healing wounds of 430 patients were treated with the composition of Example 3 of the present invention
(49 cases), surgery (197 cases), and conventional treatment (rhEGF therapy) (184 cases). There
were no statistically significant differences observed among the groups in terms of gender, age,
and wound area (p >0.05) (The comparison results of the differences in terms of various factors
are shown in Tables 5, 6 and 7).
TABLE 5
Comparison of Gender in Different Treatment Groups
Gender Group X 2 value Sig P (male/female)
This invention 41/8
Surgery group 164/33 2.360 0.307 > 0.05 Conventional 163/21 treatment
TABLE 6
Comparison of Age in Different Treatment Groups
Group Age( x±s) F value Sig P
This invention 31.04 15.49
Surgery group 29.88 17.07 0.111 0.895 >0.05 Conventional 30.41 ±16.59 treatment
TABLE 7
Comparison of Burn Wound Area in Different Treatment Groups
Group TBSA F value Sig P
This invention 1.79% ±0.01
Surgery group 2.21% ±0.01 2.837 0.060 > 0.05 Conventional 1.87% ±0.01 treatment
[0070] The wound healing of different groups (total effective rate) is shown in Table 8. Among
the 49 patients in the present invention, the wound was completely healed in 31 cases (63.27%),
effectively healed in 15 cases (30.61%), improved in 2 cases (4.08%), and not healed in 1 case
(2.04%). Among the 197 patients in the surgery group, the wound was completely healed in 152
cases (77.15%), effectively healed in 39 cases (19.80%), improved in 6 cases (3.05%), and not
healed in 0 case (0%). Among the 184 patients in the conventional treatment group, the wound
was completely healed in 96 cases (52.17%), effectively healed in 56 cases (30.43%), improved in
24 cases (13.05%), and not healed in 8 cases (4.35%). The effect of the present invention on
wound healing is analyzed by the total effective rate after receiving different treatments. The
total effective rate = (the number of completely healed cases + the number of effectively healed
cases)/total number of cases. The total effective rate of the present invention and the surgery
group in treating non-healing burn wounds was significantly higher than that of the conventional
treatment group, and the difference was statistically significant (P<0.05). However, there is no
significant difference between the total effective rate of the present invention and that of the
surgery group (P>0.05), indicating that the therapeutic effect of the present invention on the
non-healing wounds of patients is equivalent to that of the surgical group, and is significantly
better than that of the conventional treatment group.
TABLE 8
Wound Healing Assessment (Cases/Percentage)
Numb Completely Effectively Not Total Improved Group er of healed case healed healed effective X 2 test P case (%) cases (%) case(%) case(%) rate(%)
This 15 inventi 49 31(63.27%) 2(4.08%) 1 (2.04%) 93.88%1,3 (30.61%) on
Surger 152 39 y 197 6(3.05%) 0(0%) 96.95%2 (77.15%) (19.80%) 23.445 group 0.05
Conve
national 56 24 184 96(52.17%) 8(4.35%) 82.61% treatm (30.43%) (13.05%)
ent
'P < 0.05 This invention versus Conventional treatment group; 2P < 0.05 Surgery group versus
Conventional treatment group; 3 P > 0.05 This invention versus Surgery group.
[0071] The comparison of wound healing time is shown in Table 9. The wound healing time of
the present invention group, surgery group and conventional dressing group is 19.87±9.10 days,
22.71±11.77 days and 36.71±10.60 days, respectively. Compared with the conventional
treatment group, the wound healing time of the present invention group and surgery group were
significantly shorter than the conventional treatment group (P <0.05). There is no significant
difference in wound healing time between the present invention group and the surgery group
(P > 0.05). It shows that the wound healing time of the present invention is equivalent to that of
the surgery group, and is significantly shorter than that of the conventional treatment group.
TABLE 9
Wound Healing Time (Days)
Number of Wound healing time Group F P cases (X +/- S) This invention 31 19.87 ±9.10",
Surgery group 152 22.71 ±11.772 54.311 < 0.001 Conventional 96 36.71 ±10.60 treatment
'P < 0.05 This invention versus Conventional treatment group; 2P < 0.05 Surgery group versus
Conventional treatment group; 3 P > 0.05 This invention versus Surgery group.
[0072] An example of the curative effect of the present invention on human non-healing burn
wounds is shown in FIG. 10. (a) Non-healing wounds on the back of a child over 1 month. (al)
This invention applied on wounds. (a2) The wound healing at day 4 after the treatment. (b) A
non-healing wound on elbow over 1 month. (b1) This invention applied on wounds. (b2) The
wound healing at week 1 after the treatment. (b3) The wound healing at week 2 after the
treatment. (c) Non-healing wounds on the back of an adult over 1 month. (c1) This invention
applied on wounds. (c2) The wound healing at day 3 after the treatment. (c3) The wound healing
at day 7 after the treatment. (c4) The wound healing at day 10 after the treatment. The above
results show that the present invention shows significantly improved effect on wound healing
compared with that of clinical conventional treatment.
[0073] Test Example 3. Verification of the therapeutic effect of the respective compositions
prepared in Example 1 and Example 2 of the present invention on porcine full-thickness burn
wounds
[0074] The porcine full-thickness burn wound models were created with the method described
in Example 1. The respective compositions prepared in Example 1 and Example 2 of the present
invention were used to treat the wounds. rhEGF was used as a control. The wound healing time
is shown in Table 10. It is shown that the present application shortens the wound healing time
compared with rhEGF.
TABLE 10
Comparison of Wound Healing Time of the Composition Prepared in Example 1 and Example 2
Number of Wound healing time Group F P Cases (days)( X+/-S)
Example 1 9 19.35 ±4.211,3 23.45
Example 2 9 20.61 ±2.831,3 22.98 < 0.001 rhEGF 9 23.56 4.852
Saline 9 32.56 5.36
'P<0.05, This invention versus Saline group; 2P<0.05, rhEGF versus Saline group; 3 P<0.05, This
invention versus rhEGF.
[0075] The descriptions above are only the preferred embodiments of the present invention and
are not intended to limit the present invention. Any modification, equivalent replacement,
improvement, etc. made within the spirit and principle of the present invention shall be included
in the protection scope of the present invention.
EDITORIAL NOTE 2021101843
There are 5 pages of claims only

Claims (9)

1. A composition for treating a burn wound, wherein the composition comprises the following ingredients in mass content: a fatty acid 261-639mg, an organic substance 3.5 350mg, a carbohydrate 0.02-60mg, a vitamin 9-13pg, a microelement 3.04-5.5mg, an antibiotic 0.6-70mg, and an amino acid 105-335mg.
2. A composition for treating a burn wound, wherein the composition comprises the following ingredients in parts by weight: 261-639 parts of a fatty acid, 3.5-350 parts of an organic substance, 0.02-60 parts of a carbohydrate, 0.009-0.013 parts of vitamin E, 3.04-5.5 parts of a microelement, 0.6-70 parts of an antibiotic, and 105-335 parts of an amino acid;
wherein,
the fatty acid is at least one selected from the group consisting of oleic acid, linoleic acid, palmitic acid and linolenic acid;
the organic substance is at least one selected from the group consisting of ellagic acid, hypaphorine, huperzine C, huperzine A, harmalol, abrine, berberine hydrochloride, 10-gingerol, methyl gallate, spathulenol, 3-furylmethyl 1H-pyrrole-2 carboxylate, tanshinone, dihydrocapsaicin, potassium 7- hydroxy-1-naphthalenesulfonate, pilocarpine, adenosine, firmanoic acid, glabrolide, liquidambaric lactone, schisandrolactone, dehydroepiandrosterone, 11(13) dehydroivaxillin, 2-hydroxyeupatolide, 14,15beta dihydroxyklaineanone, olaquindox, oridonin, phorbol, harmine, maltol, hypaconine, 2-0-rhamnosylicariside II, theobromine, theophylline, hordenine, and ephedrine; the carbohydrate is at least one selected from the group consisting of fructose and glucose; the microelement is at least one selected from the group consisting of calcium, iron, zinc, copper, and phosphorus; the antibiotic is at least one selected from the group consisting of mupirocin, neomycin, polymyxin B, gentamicin, amphotericin B and vancomycin; and the amino acid is at least one selected from the group consisting of glutamic acid, arginine, aspartic acid, serine, glycine, alanine, tyrosine, histidine, proline, cysteine, valine, isoleucine, leucine, phenylalanine, methionine, threonine, and lysine.
3. The composition according to claim 2, wherein the fatty acid further comprises at least one selected from the group consisting of stearic acid, butyric acid, hexanoic acid, octanoic acid, myristic acid, palmitoleic acid, heptadecanoic acid, eicosanoic acid, and cis-11-eicosenoic acid; wherein, in parts by weight, the total content of oleic acid, linoleic acid, palmitic acid, and linolenic acid is not less than 250 parts.
4. The composition according to claim 3, wherein, in parts by weight, the fatty acid comprises: 20-50 parts of palmitic acid, 10 parts of stearic acid, 100-200 parts of oleic acid, 100-300 parts of linoleic acid, 30-50 parts of linolenic acid, 0.1-1 parts of butyric acid, 0.1-1 parts of hexanoic acid, 0.1-1 parts of octanoic acid, 0.1-1 parts of myristic acid, 0.1-1 parts of palmitoleic acid, 0.1-1 parts of heptacarbonic acid, 0.1-1 parts of eicosanoic acid, and 0.3-2 parts of cis-11-eicosaenoic acid.
5. The composition according to claim 2, wherein, in parts by weight, the organic substance comprises: 0.1-10 parts of ellagic acid, 0.1-10 parts of hypaphorine, 0.1-10 parts of huperzine C, 0.1-10 parts of huperzine A, 0.1-10 parts of harmalol, 0.1-10 parts of abrine, 0.1-10 parts of berberine hydrochloride, 0.1-10 parts of 10-gingerol, 0.1-10 parts of methyl gallate, 0.1-10 parts of spathulenol, 0.1-10 parts of 3-furylmethyl 1H-pyrrole-2 carboxylate, 0.1-10 parts of tanshinone, 0.1-10 parts of dihydrocapsaicin, 0.1-10 parts of potassium 7-hydroxy-1 naphthalenesulfonate, 0.1-10 parts of pilocarpine, 0.1-10 parts of adenosine, 0.1-10 parts of firmanoic acid, 0.1-10 parts of glabrolide, 0.1-10 parts of liquidambaric lactone, 0.1-10 parts of schisanlactone, 0.1-10 parts of dehydroepiandrosterone, 0.1-10 parts of 11(13)-dehydroivaxillin, 0.1-10 parts of 2 hydroxyzeranolide, 0.1-10 parts of 14,15beta dihydroxyklaineanone, 0.1-10 parts of olaquindox, 0.1-10 parts of oridonin, 0.1-10 parts of phorbol, 0.1-10 parts of harmine, 0.1 parts of maltol, 0.1-10 parts of hypaconine, 0.1-10 parts of 2 -rhamnosylicariside II, 0.1-10 parts of theobromine, 0.1-10 parts of theophylline, 0.1-10 parts of hordeine, and 0.1-10 parts of ephedrine.
6. The composition according to claim 2, wherein, in parts by weight, the carbohydrate comprises 0.01-30 parts of glucose and 0.01-30 parts of fructose.
7. The composition according to claim 2, wherein, in parts by weight, the microelement includes: 0.5-1 parts of calcium, 0.01 0.1 parts of iron, 0.02-0.2 parts of zinc, 0.01-0.2 parts of copper, and 2.5-4 parts of phosphorus.
8. The composition according to claim 2, wherein, in parts by weight, the antibiotic comprises: 0.1-20 parts of mupirocin, 0.1 parts of neomycin, 0.1-10 parts of polymyxin B., 0.1-10 parts of gentamicin, 0.1-10 parts of amphotericin B, and 0.1-10 parts of vancomycin.
9. The composition according to claim 2, wherein, in parts by weight, the amino acid comprises: 20-50 parts of glutamic acid, -40 parts of arginine, 10-30 parts of aspartic acid, 5-20 parts of serine, 5-20 parts of glycine, 5-20 parts of alanine, 5-20 parts of tyrosine, 1-10 parts of histidine, 1-10 parts of proline, 1-10 parts of cysteine, 5-10 parts of valine, 5-10 parts of isoleucine, -30 parts of leucine, 5-20 parts of phenylalanine, 1-5 parts of methionine, 2-15 parts of threonine, and 4-15 parts of lysine.
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