CN107789393A - A kind of pharmaceutical composition for treating wound caused by chemicotherapy - Google Patents
A kind of pharmaceutical composition for treating wound caused by chemicotherapy Download PDFInfo
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- CN107789393A CN107789393A CN201610753452.6A CN201610753452A CN107789393A CN 107789393 A CN107789393 A CN 107789393A CN 201610753452 A CN201610753452 A CN 201610753452A CN 107789393 A CN107789393 A CN 107789393A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/19—Acanthaceae (Acanthus family)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
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- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract
The invention discloses a kind of pharmaceutical composition for treating wound caused by chemicotherapy, the new pharmaceutical composition is made up of the composition of following weight：8 parts of chitosan oligomer 2 part, fall 2 parts of certain herbaceous plants with big flowers extract 1 part, 1.5 parts of Chinese mesona herb extract 0.5 part, 1.5 parts of folium eucalypti extract 0.5 part, 1 part of ivy extract 0.5 part, purple 1 part of indigo extract 0.5 part, 0.75 part of RADIX ACHYRANTHIS LONGIFOLIAE extract 0.25 part.The present inventor has carried out acute toxicity testing to described pharmaceutical composition, as a result shows that the pharmaceutical composition of the present invention can be considered nontoxic.Antibacterial experiment in vitro shows that the drug regimen has good inhibition to staphylococcus aureus, Escherichia coli, pseudomonas aeruginosa.Wound repair experiment shows that the pharmaceutical composition has good effect to wound healing.Cell proliferation experiment shows that the pharmaceutical composition has good cell repair and regeneration function.Zoopery explanation has significant effect to wound healing caused by treatment chemicotherapy.Therefore, pharmaceutical composition of the invention has larger clinical value and social benefit available for wound healing caused by treatment chemicotherapy.Preparation method of the present invention is simple, is suitable for industrialized production.
Description
Technical field
The present invention relates to pharmaceutical composition, and in particular to a kind of pharmaceutical composition for treating wound caused by chemicotherapy.
Background technology
Due to the change of environment and the increase of operating pressure, cancer patient is more and more, and many patients pass through chemicotherapy
To treat, while curing the disease, many wounds can be also produced on patient body, and these wounds are difficult to heal, and not only increase
The pain of patient, it is also easy to make patient to endanger patient body by bacterium superinfection.So accelerate wound caused by chemicotherapy
Healing is the very urgent thing of part.
At present, based on the research to chitosan, having reported it has antibacterial, antitumor, Adjust-blood lipid, regulation immune and promotees
Enter the multiple functions such as wound reparation, but because of its poorly water-soluble, greatly limit the application in biomedicine field.The present inventor is led to
Enzyme edman degradation Edman is crossed, by degradation of chitosan into the degree of polymerization is small, water-soluble big chitosan oligomer.And it has been investigated that oligomeric shell
Glycan has free amine group, can be combined with negatively charged cell membrane rapidly, strengthens bacterial cell membrane permeability, cell content
Beyond the region of objective existence stream, so as to bacteria growing inhibiting；Chitosan can accelerate the secretion of collagen, so as to promote granulation tissue and epithelium group
The formation knitted, promote the quick healing of wound.
However, the present inventor further study show that, as individually by chitosan oligomer be used for treat chemicotherapy caused by wound
During mouthful healing, effect is not notable, and when adding other compositions pharmaceutical composition is made, it has more preferable treatment to wound healing
Effect, available for therapeutic wound healing caused by chemicotherapy.Thus, preferably actively research oligopolymerization chitosan sugar composite and its new adaptation
Disease.
The content of the invention
The technical problems to be solved by the invention are to overcome above-mentioned weak point, medicine of the research and design containing chitosan oligomer
Compositions and its clinical practice.
The invention provides a kind of pharmaceutical composition for treating wound healing caused by chemicotherapy.
The pharmaceutical composition of the present invention is made up of the composition of following weight：2 parts -8 parts of chitosan oligomer, falls certain herbaceous plants with big flowers and carries
Take 1 part -2 parts of thing, 0.5 part -1.5 parts of Chinese mesona herb extract, 0.5 part -1.5 parts of folium eucalypti extract, 0.5 part -1 of ivy extract
Part, purple 0.5 part -1 part of indigo extract, 0.25 part -0.75 part of RADIX ACHYRANTHIS LONGIFOLIAE extract.
Preferable formula, pharmaceutical composition of the invention are made up of the composition of following weight proportion：5 parts of chitosan oligomer,
Fall 1.5 parts of certain herbaceous plants with big flowers extract, 1 part of Chinese mesona herb extract, 1 part of folium eucalypti extract, 0.75 part of ivy extract, purple indigo extract
0.75 part, 0.5 part of RADIX ACHYRANTHIS LONGIFOLIAE extract.
In pharmaceutical composition of the present invention, the mean molecule quantity of the chitosan oligomer is 1000-2500, by following
It is prepared by method：
By the chitosan 10g acetic acids that 330ml concentration is 1%, chitosan concentration 0.03g/ml, papain is added
With the mixed enzyme 5ml of bromelain composition（45u containing enzyme amount）Hydrolysis, pH value is adjusted to 6.5,50 DEG C of continuation after hydrolyzing 20mim
Degrade 4.5h, 100 DEG C of enzyme deactivation 15min, centrifuging and taking supernatant, freeze-drying, obtains chitosan oligomer 9.27g.Tested through HPLC, really
It is chitosan oligomer to recognize it, mean molecule quantity 1750.
It is described fall certain herbaceous plants with big flowers extract, Chinese mesona herb extract, folium eucalypti extract, ivy extract, purple indigo extract, RADIX ACHYRANTHIS LONGIFOLIAE
The raw materials such as extract are by being commercially available.
It is yet another object of the invention to provide described pharmaceutical composition to prepare Wound medicine caused by treatment chemicotherapy
In application.
The present inventor has carried out acute toxicity testing to described pharmaceutical composition, as a result shows the pharmaceutical composition of the present invention
It can be considered nontoxic.Antibacterial experiment in vitro shows the drug regimen to staphylococcus aureus, Escherichia coli, pseudomonas aeruginosa
There is good inhibition.Wound repair experiment shows that the pharmaceutical composition has good effect to wound healing.Cell increases
Grow experiment and show that the pharmaceutical composition has good cell repair and regeneration function.
The pharmaceutical composition of the present invention solves the problems, such as that other clinical medicine toxicity are big or wound repairing effect is bad,
Pharmaceutical composition of the present invention is non-toxic, significant effect, has larger clinical value for treating wound caused by chemicotherapy
And social benefit.Preparation method of the present invention is simple, is suitable for industrialized production.
Embodiment
The preparation of the chitosan oligomer of embodiment 1（Enzyme process）.
By chitosan 10g（Degree of deacetylation 95%, moisture 4.85%, ash content 0.5%, mean molecule quantity 100,000, purchased from Jinan
Hai get Bei ocean engineerings Co., Ltd）Dissolved with the acetic acid 330ml that concentration is 1%, chitosan concentration 0.03g/ml, add wood
The mixed enzyme 5ml of melon protease and bromelain composition（45u containing enzyme amount）Hydrolysis, pH value is adjusted to 6.1 after hydrolyzing 20mim,
50 DEG C are continued the 4.5h that degrades, and 100 DEG C of enzyme deactivation 15min, centrifuging and taking supernatant, freeze-drying, obtain chitosan oligomer 9.27g.Through
HPLC is tested, and confirms as chitosan oligomer, mean molecule quantity 1750.
The preparation of the pharmaceutical composition of embodiment 2.
Chitosan oligomer purity >=98%, mean molecule quantity 1750, embodiment 1 are made.
Following composition raw material is commercially available：
Fall certain herbaceous plants with big flowers extract total starches content >=40%；
Chinese mesona herb extract Chinese mesona herb polyoses content >=30%；
Big fruit eucalyptus aldehyde >=10% of folium eucalypti extract；
Ivy extract hederin content >=8%；
Purple indigo extract α-amyrin content >=8%；
RADIX ACHYRANTHIS LONGIFOLIAE extract triterpenoid saponin content >=6%.
200ml beakers are taken, 100ml is added and removes thermal source distilled water, then add 5g chitosan oligomers, 1.5g falls certain herbaceous plants with big flowers extraction
Thing, 1.0g Chinese mesona herb extracts, 1.0g folium eucalypti extracts, 0.75g ivy extracts 0.75g, purple indigo extract 0.75g are red
Achyranthes bidentata extract 0.5g, being sufficiently stirred makes it well mixed, boils 5min, is cooled to 25 DEG C of room temperature, is filtered to remove insoluble matter, i.e.,
Obtain pharmaceutical composition 106.5g.
Pharmaceutical composition made from embodiment 2 is used for following experiments.
The acute toxicity testing of embodiment 3.
Experimental animal：Kunming mice 70,17 ~ 22g of body weight, male and female half and half are limited purchased from Shanghai Si Laike experimental animals
Company.
Animal packet：Distinguish the Stochastic Equilibrium method of dividision into groups using male and female, be divided into 7 groups, every group 10, one of which is blank
Control group.
Laboratory sample：It is made in embodiment 2.
Dosage determines：Dose design is 3ml/kg, 10ml/kg, 50ml/kg, 100ml/kg.
Administration：Disposable gastric infusion：3 ~ 5h of fasting before administration, after administration 1 ~ 2h of fasting, fasting can't help water.Using in batches
Administration, control group, 3ml/kg groups, 10ml/kg groups first administrations, determined after administration set by dosage it is suitable, then give 50ml/kg
Group and 100ml/kg groups.Continuous Observation more than 7 days after administration, then morning and afternoon is respectively observed once daily, Continuous Observation 14 days.In detail
Every observation index is carefully recorded, is shown in Table 1.
Table 1.
| Group | Dosage（ml/kg） | Quantity（Only） | Survival rate（%） |
| 1 | 0 | 10 | 100 |
| 2 | 3 | 10 | 100 |
| 3 | 10 | 10 | 100 |
| 4 | 50 | 10 | 100 |
| 5 | 100 | 10 | 100 |
Conclusion：Tested material is when gastric infusion dosage reaches 100ml/kg in this experiment（Solid equivalent to 7.5mg/kg
Medicine）, do not occur death.Judge according to acute toxicity grading criteria, this test medicine can be considered nontoxic.
The antibacterial experiment in vitro of embodiment 4.
Bacterial strain：Staphylococcus aureus, Escherichia coli, pseudomonas aeruginosa.
Buffer solution：PH7.0 sterile NaCl peptone buffer agents.
Culture medium：Plain agar culture medium.
Laboratory sample：Embodiment 2 is made.
Experimental temperature：20℃±1℃.
Experimental method：At 20 DEG C ± 1 DEG C, it is false that laboratory sample is acted on into staphylococcus aureus, Escherichia coli, verdigris
Monad, action time 2min, 5min, 10min, 20min, observation experiment result.Experiment is repeated 3 times.Experimental result is shown in Table
2。
Table 2.
Conclusion：At 20 DEG C ± 1 DEG C, tested material has to staphylococcus aureus, Escherichia coli, pseudomonas aeruginosa
Extremely strong bacteriostasis.
The mucocutaneous impaired wound repair experiment of embodiment 5.
Experimental animal：C57 mouse, 16-18g, female, purchased from Shanghai Si Kelai experimental animals Co., Ltd.
Experimental method：By experiment mice blank group, control group 1（U.S.'s 3M medical adhesive tapes）, control group 2（Your treasured Britain applies
Convatee products）, control group 3（Golden English peptide EGF）, experimental group.Every group 20.Mouse back unhairing otch modeling, the surface of a wound are used
Iodophor disinfection, then with appropriate physiological saline debridement, the product of control group 1 then is covered in relatively face respectively, control group 2 produces
Product；The product of control group 3 and experimental group medicine are sprayed, spontaneously dries, is then covered with sterile gauze.Respectively with regard to 3 days, 7 days and 14
It wound is replied situation and compareed, and the results are shown in Table 3.
Table 3.
Conclusion：Healed substantially during experimental group 7 days, better than control group.
The cell proliferation experiment of embodiment 6.
Cell line：People's epidermis protein cell line colo-16.
Reagent：Culture medium：DMEM, containing 10% hyclone, 100ug/ml penicillin, 100ug/ml streptomysin；
MTT, the solution of 5mg/ml concentration is made into using the preceding PBS with PH7.2.
DMSO is inoculated with epidermal cell:When the colo-16 cell growths of culture are close to individual layer, supernatant in bottle is drawn, is used
0.3% Trypsin Induced, adds appropriate DMEM that cell monolayer suspension, inoculation and 96 orifice plates are made, and 37 DEG C 5% is put per hole 200uL
CO2gas incubator culture.
Drug-treated：After inoculation 24 hours, each hole supernatant and non-attached cell are drawn, is separately added into control group 1（Peace
Skin relaxes）, control group 2（Golden English peptide EGF）, experimental group.After dosing, continue culture 72 hours, cell is observed under inverted microscope
Proliferative conditions, experimental result are shown in Table 4.
Table 4.
| Group | Cell breeds OD values |
| Control group 1 | 0.18±0.030 |
| Control group 2 | 0.20±0.035 |
| Experimental group | 0.40±0.045 |
Conclusion：Drug regimen is good to the propagation and regeneration function of cell.
Claims (6)
1. a kind of pharmaceutical composition for treating wound caused by chemicotherapy, it is characterised in that described pharmaceutical composition is by following heavy
Measure the composition composition of part proportioning：2 parts -8 parts of chitosan oligomer, fall 1 part -2 parts of certain herbaceous plants with big flowers extract, 0.5 part -1.5 of Chinese mesona herb extract
Part, 0.5 part -1.5 parts of folium eucalypti extract, 0.5 part -1 part of ivy extract, purple 0.5 part -1 part of indigo extract, RADIX ACHYRANTHIS LONGIFOLIAE extraction
0.25 part -0.75 part of thing.
2. a kind of pharmaceutical composition for treating wound healing caused by chemicotherapy, it is characterised in that described pharmaceutical composition is under
The composition composition of row weight：5 parts of chitosan oligomer, fall 1.5 parts of certain herbaceous plants with big flowers extract, 1 part of Chinese mesona herb extract, folium eucalypti extraction
1 part of thing, 0.75 part of ivy extract, purple 0.75 part of indigo extract, 0.5 part of RADIX ACHYRANTHIS LONGIFOLIAE extract.
3. the chitosan oligomer is prepared by the following method：
By the chitosan 10g acetic acids that 330ml concentration is 1%, chitosan concentration 0.03g/ml, papain is added
With the mixed enzyme 5ml of bromelain composition（45u containing enzyme amount）Hydrolysis, pH value is adjusted to 6.5,50 DEG C of continuation after hydrolyzing 20mim
Degrade 4.5h, 100 DEG C of enzyme deactivation 15min, centrifuging and taking supernatant, freeze-drying, obtains chitosan oligomer 9.27g.
4. preparation method according to claim 3, it is characterised in that the mean molecule quantity of the chitosan oligomer is
1000-2500。
A kind of 5. pharmaceutical composition as claimed in claim 1 answering in wound healing medicine caused by treatment chemicotherapy is prepared
With.
A kind of 6. pharmaceutical composition as claimed in claim 2 answering in wound healing medicine caused by treatment chemicotherapy is prepared
With.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610753452.6A CN107789393A (en) | 2016-08-29 | 2016-08-29 | A kind of pharmaceutical composition for treating wound caused by chemicotherapy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610753452.6A CN107789393A (en) | 2016-08-29 | 2016-08-29 | A kind of pharmaceutical composition for treating wound caused by chemicotherapy |
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| CN107789393A true CN107789393A (en) | 2018-03-13 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201610753452.6A Pending CN107789393A (en) | 2016-08-29 | 2016-08-29 | A kind of pharmaceutical composition for treating wound caused by chemicotherapy |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102727578A (en) * | 2011-04-11 | 2012-10-17 | 苏州瑞美科生物技术有限公司 | Pharmaceutical composition for healing wounds generated by chemoradiotherapy |
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2016
- 2016-08-29 CN CN201610753452.6A patent/CN107789393A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102727578A (en) * | 2011-04-11 | 2012-10-17 | 苏州瑞美科生物技术有限公司 | Pharmaceutical composition for healing wounds generated by chemoradiotherapy |
Non-Patent Citations (2)
| Title |
|---|
| 俞露等: "低聚壳聚糖的性质和应用研究 ", 《河南科技学院学报》 * |
| 段杉等: "低聚壳聚糖的制备及应用 ", 《中国食品添加剂》 * |
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Application publication date: 20180313 |