CN106265112B - Promote the drug or cosmetic composition of wound healing - Google Patents
Promote the drug or cosmetic composition of wound healing Download PDFInfo
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- CN106265112B CN106265112B CN201510325412.7A CN201510325412A CN106265112B CN 106265112 B CN106265112 B CN 106265112B CN 201510325412 A CN201510325412 A CN 201510325412A CN 106265112 B CN106265112 B CN 106265112B
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Abstract
Disclose the purposes of formula a and formula b compound represented or its pharmaceutically acceptable salt in the drug or cosmetic composition that preparation promotes wound healing:
Description
Technical field
The application relates generally to medicine and cosmetic field.Specifically, this application involves isosulfocyanate compounds to exist
The drug or the purposes in cosmetic composition that preparation promotes the wound healing including exedens wound.
Background technique
Papaya (Carica Papaya L.) is a kind of tropical evergreen fruit tree.Primary chemical contained in papaya seed at
It is divided into benzyl isothiocyanate.Have reported the anticancer usage of benzyl isothiocyanate in papaya seed extract.Isothiocyanic acid benzyl
Ester (Benzyl-isothiocyanate, BITC) structure is as shown in formula a:
Radish seed is Chinese herbal medicine simply, and Latin literary fame: Semen Raphani is the maturation of crucifer radish
Seed.Radish seed is usually used in alleviating stagnation of QI due to dyspepsia, abdominal fullness and distention, belch, the symptoms such as weight, coughing with a lot of sputum, syndrome characterized by dyspnea fullness sensation in chest after diarrhea.
Modern Pharmacognosy result of study discovery, principle active component be raphanin (Sulforaphene is abbreviated as SFE, molecular formula:
C6H9NOS2), it is a kind of isosulfocyanate compound, structure is as shown in formula b:
The wound healing of skin histology is extremely complex repair process.Under normal circumstances, the process of wound healing can
To be divided into three phases: initial inflammation phase, is directly followed by tissue remodeling and proliferation, after but the stage of ripeness.In maturation
Re-epithelialization, skin heart generation and wound closure occur in stage.Re-epithelialization is related to epithelial tissue, and mainly cutin is formed
The migration and proliferation of cell.Callus mouth is not most commonly in trauma wounds, and operation wound wound suffers from diabetes, phlebostasis disease
In sick patient and sickbed patients.Therefore, the drug of wound healing or cosmetic composition is promoted to have greatly using valence
Value and economic benefit.
Summary of the invention
The application relates in one aspect to formula a or formula b compound represented or its pharmaceutically acceptable salt and promotes wound in preparation
The drug of healing or the purposes in cosmetic composition:
The another aspect of the application is related to promoting the method for the wound healing of individual comprising to the individual giving construction a
Or formula b compound represented or its pharmaceutically acceptable salt:
The another aspect of the application be related to for promote individual wound healing formula a formula b compound represented or its
Pharmaceutically acceptable salt:
The another aspect of the application is related to pharmaceutical composition or cosmetic composition for promoting the wound healing of individual,
It includes formula a or formula b compound represented or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier, excipient or diluent
Or the acceptable carrier or medium of cosmetic:
Detailed description of the invention
Fig. 1 shows the effect picture of compound raphanin (15mM) treatment animal wound Healing Experiments.
Fig. 2 shows the skin histology HE slicing experiment effect pictures after compound radish extract for treating skin wound.Wherein:
(a) control group (non-administration)；(b) after representation compound raphanin (15mM) is administered 8 days.
Specific embodiment
In the following description, including certain concrete details are to provide comprehensive reason to each disclosed embodiment
Solution.However, those skilled in the relevant art are not, it will be recognized that use one or more of these concrete details, and use other
Embodiment can be achieved in the case where method, component, material etc..
Unless required in addition of the application, in claims in the whole instruction and thereafter, word " comprising " and " packet
Containing " it should be interpreted that meaning open, including formula, i.e., " including but not limited to ".
" embodiment " mentioned in entire this specification or " embodiment " or " in another embodiment " or
" in certain embodiments " mean include in an at least embodiment it is relevant to described in the embodiment with specific reference to
Element, structure or feature.Therefore, throughout the specification different location occur phrase " in one embodiment " or " in reality
Apply in scheme " or " in another embodiment " or " in certain embodiments " same embodiment need not be all referred to.In addition,
Key element, structure or feature can combine in one or more embodiments in any suitable manner.
The application relates in one aspect to formula a or formula b compound represented or its pharmaceutically acceptable salt and promotes wound in preparation
The drug of healing or the purposes in cosmetic composition:
In certain embodiments, the drug and cosmetic composition are used for local application, including but not limited to soft
Paste, cream, emplastrum, paste, gelling agent, lotion, liniment, emulsion, solution, suspension, powder, granule, patch,
Paint, dressing, sponginum, spray and/or aerosol form are used for local application.
In certain embodiments, the drug is for being administered orally, including but not limited to tablet, capsule, emulsion,
Solution, suspension, powder or granular form are administered orally.
In certain embodiments, the drug is used for Formulations for systemic administration, and preferably intravascular injection is administered, including intravascular
Dropleting medicine-feeding, Intravascular infusions administration and intravascular bolus administration, are administered more preferably in the form of injection for intravascular injection.
In certain embodiments, the wound includes but is not limited to skin injury, mucosa injury and tissue damage.
In certain embodiments, the wound includes but is not limited to trauma wounds, surgical wound, tans severely, burns, ulcer
Property wound, bedsore and diabetic ulcer wound.
In certain embodiments, the exedens wound includes but is not limited to gastric ulcer and canker sore.
In certain embodiments, when the drug or cosmetic composition are used for local application, the formula a and formula b
Compound represented or the content of its pharmaceutically acceptable salt are each independently the 0.1 weight % of weight %~10.0, preferably
The 0.1 weight % of weight %~5.0, more preferably 0.5 weight %-3.0 weight %.
In certain embodiments, when the drug is for oral give, the formula a and formula b compound represented or
The content of its pharmaceutically acceptable salt is each independently 0.01 weight %-20 weight %, preferably 0.1 weight %-10 weight
Measure %, more preferably 0.1 weight %-5.0 weight %.
In certain embodiments, when the drug is administered for intravascular injection, chemical combination shown in the formula a and formula b
The content of object or its pharmaceutically acceptable salt is each independently the 0.01 weight weight % of %~20.0, preferably 0.1 weight %-
5.0 weight %.
In certain embodiments, the drug or cosmetic composition with once a day, twice daily, three times a day,
Five frequencies are administered four times per day or daily.
The another aspect of the application is related to promoting the method for the wound healing of individual comprising to the individual giving construction a
Or formula b compound represented or its pharmaceutically acceptable salt:
In certain embodiments, by the formula a or formula b compound represented or its pharmaceutically acceptable salt with drug or
The form of cosmetic composition gives the individual.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt with drug or
When the form local application of cosmetic composition, the drug or cosmetic composition include but is not limited to ointment, cream,
Emplastrum, paste, gelling agent, lotion, liniment, emulsion, solution, suspension, powder, granule, patch, paint, dressing, sea
The forms such as continuous agent, spray and/or aerosol.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with drug
Form is administered orally, and the drug includes but is not limited to tablet, capsule, emulsion, solution, suspension, powder or granule
Etc. forms.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with drug shape
When formula Formulations for systemic administration, preferably intravascular injection is administered, including the administration of intravascular dropleting medicine-feeding, Intravascular infusions and intravascular group
Note administration, is administered more preferably in the form of injection for intravascular injection.
In certain embodiments, the wound includes but is not limited to skin injury, mucosa injury and tissue damage.
In certain embodiments, the wound includes but is not limited to trauma wounds, surgical wound, tans severely, burns, ulcer
Property wound, bedsore and diabetic ulcer wound.
In certain embodiments, the exedens wound includes but is not limited to gastric ulcer and canker sore.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with the medicine
When object or cosmetic composition form local application, content is each independently the 0.1 weight % of weight %~10.0, preferably
The 0.1 weight % of weight %~5.0, more preferably 0.5 weight %-3.0 weight %.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with the medicine
When object form is administered orally, content is each independently 0.01 weight %-20 weight %, preferably 0.1 weight %-10 weight
Measure %, more preferably 0.1 weight %-5.0 weight %.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with injection shape
When formula is administered for intravascular injection, content is each independently the 0.01 weight % of weight %~20.0, preferably 0.1 weight
Measure %-5.0 weight %.
In certain embodiments, the formula a or formula b compound represented or its pharmaceutically acceptable salt are with drug or change
The form of adornment composition is applied with five times once a day, twice daily, three times a day, four times per day or daily frequencies
With.
The therapeutically effective amount of compound shown in the formula a or formula b of the application depends on administration route and individual to be administered
Physical trait.Adjustable dosage is to reach desired effect, but this will depend on following factors: weight, diet, simultaneously
Drug therapy and other medical domains the other factors generally acknowledged of technical staff.More specifically, therapeutically effective amount refers to effectively
Disease symptoms are prevented, mitigated or improved, or extend the amount for receiving the compound for the treatment of individual life span.The reality of those skilled in the art
Border ability can determine therapeutically effective amount well, especially in accordance with detailed disclosure provided by the present invention.
As is apparent to those of skill in the art, dosage to be administered in the application and specific method of application will
Change depending on individual age, weight and used particular compound.Those skilled in the art use conventional medicine
Method of science can reach the purpose of determining effective quantity level, that is, achieve the purpose that dosage level necessary to determining desired effect.
In general, being applied with the human clinical that relatively low-dose level starts to carry out compound, as being increased up for dosage level reaches institute
Desired effect.Alternatively, being able to use acceptable in vitro study using the pharmacological method established to establish this method mirror
The effective quantity and administration route of compound shown in fixed formula a or formula b.
For example, when formula a or formula b compound represented or its pharmaceutically acceptable salt are in the form of drug or cosmetic composition
When local application, dosage is every time application 0.2g-10g drug or cosmetic composition, and frequency of administration is once a day to every
Day five times；Preferably, dosage is every time application 2g-5g drug or cosmetic composition, and frequency of administration is twice a day to every
Day is three times.
For example, when formula a or formula b compound represented or its pharmaceutically acceptable salt in the form of drug (for example, injection) into
When promoting circulation of blood pipe inner injecting and administering, dosage is to give 0.1ml-5ml drug every time, and administration frequency is once a day to daily five
It is secondary；Preferably, dosage is every time application 0.5ml-2ml drug, and administration frequency is twice a day to three times a day.
For example, when formula a or formula b compound represented or its pharmaceutically acceptable salt are administered orally with medicament forms,
Dosage is that 5mg-500mg drug is given once daily, and 10mg-100mg drug is preferably given once daily, and is divided once a day to five times a day
It gives, preferably divides two times a day to three times per day giving.
The another aspect of the application be related to for promote individual wound healing formula a formula b compound represented or its
Pharmaceutically acceptable salt:
In certain embodiments, the formula a or formula b compound represented or its pharmaceutically acceptable salt are with drug or change
The form of adornment composition gives the individual.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt with drug or
When the form local application of cosmetic composition, the drug or cosmetic composition include but is not limited to ointment, cream,
Emplastrum, paste, gelling agent, lotion, liniment, emulsion, solution, suspension, powder, granule, patch, paint, dressing, sea
The forms such as continuous agent, spray and/or aerosol.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with drug
Form is administered orally, and the drug includes but is not limited to tablet, capsule, emulsion, solution, suspension, powder or granule
Etc. forms.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with drug shape
When formula Formulations for systemic administration, preferably intravascular injection is administered, including the administration of intravascular dropleting medicine-feeding, Intravascular infusions and intravascular group
Note administration, is administered more preferably in the form of injection for intravascular injection.
In certain embodiments, the wound includes but is not limited to skin injury, mucosa injury and tissue damage.
In certain embodiments, the wound includes but is not limited to trauma wounds, surgical wound, tans severely, burns, ulcer
Property wound, bedsore and diabetic ulcer wound.
In certain embodiments, the exedens wound includes but is not limited to gastric ulcer and canker sore.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with the medicine
When object or cosmetic composition form local application, content is each independently the 0.1 weight % of weight %~10.0, preferably
The 0.1 weight % of weight %~5.0, more preferably 0.5 weight %-3.0 weight %.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with the medicine
When object form is administered orally, content is each independently 0.01 weight %-20 weight %, preferably 0.1 weight %-10 weight
Measure %, more preferably 0.1 weight %-5.0 weight %.
In certain embodiments, when the formula a or formula b compound represented or its pharmaceutically acceptable salt are with injection shape
When formula is administered for intravascular injection, content is each independently the 0.01 weight % of weight %~20.0, preferably 0.1 weight
Measure %-5.0 weight %.
In certain embodiments, the formula a or formula b compound represented or its pharmaceutically acceptable salt are with drug or change
The form of adornment composition is applied with five times once a day, twice daily, three times a day, four times per day or daily frequencies
With.
In certain embodiments, when formula a or formula b compound represented or its pharmaceutically acceptable salt are with drug or makeup
When with composition forms local application, dosage is that application 0.2g-10g drug or cosmetic composition, frequency of administration are every time
Once a day to five times a day；Preferably, dosage is that application 2g-5g drug or cosmetic composition, frequency of administration are every time
Twice a day to three times a day.
In certain embodiments, when formula a or formula b compound represented or its pharmaceutically acceptable salt are with medicament forms mouth
When clothes application, dosage is that 5mg-500mg drug is given once daily, and 10mg-100mg drug is preferably given once daily, and is divided one day one
It is secondary to five times a day giving, preferably divide two times a day to three times per day giving.
In certain embodiments, when formula a or formula b compound represented or its pharmaceutically acceptable salt with drug (for example,
Injection) for form when carrying out intravascular injection administration, dosage is to give 0.1ml-5ml drug every time, and administration frequency is daily one
It is secondary to five times a day；Preferably, dosage is every time application 0.5ml-2ml drug, and administration frequency is twice a day to daily three
It is secondary.
The another aspect of the application is related to pharmaceutical composition or cosmetic composition for promoting the wound healing of individual,
It includes formula a or formula b compound represented or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier, excipient or diluent
Or the acceptable carrier or medium of cosmetic:
In certain embodiments, described pharmaceutical composition and cosmetic composition are used for local application, including but unlimited
In with ointment, cream, emplastrum, paste, gelling agent, lotion, liniment, emulsion, solution, suspension, powder, particle
Agent, patch, paint, dressing, sponginum, spray and/or aerosol form are used for local application.
In certain embodiments, described pharmaceutical composition is for being administered orally, including but not limited to tablet, capsule
Agent, emulsion, solution, suspension, powder or granular form are administered orally.
In certain embodiments, described pharmaceutical composition is used for Formulations for systemic administration, and preferably intravascular injection is administered, including
Intravascular dropleting medicine-feeding, Intravascular infusions administration and intravascular bolus administration, are used for intravascular injection more preferably in the form of injection
Administration.
In certain embodiments, the wound includes but is not limited to skin injury, mucosa injury and tissue damage.
In certain embodiments, the wound includes but is not limited to trauma wounds, surgical wound, tans severely, burns, ulcer
Property wound, bedsore and diabetic ulcer wound.
In certain embodiments, the exedens wound includes but is not limited to gastric ulcer and canker sore.
In certain embodiments, when described pharmaceutical composition or cosmetic composition are used for local application, the formula a
It is each independently 0.1 weight of weight %~10.0 % with the content of formula b compound represented or its pharmaceutically acceptable salt, it is excellent
It is selected as the 0.1 weight % of weight %~5.0, more preferably 0.5 weight %-3.0 weight %.
In certain embodiments, when the drug is for when being administered orally, the formula a and formula b compound represented or
The content of its pharmaceutically acceptable salt is each independently 0.01 weight %-20 weight %, preferably 0.1 weight %-10 weight
Measure %, more preferably 0.1 weight %-5.0 weight %.
In certain embodiments, described when being used for intravascular injection administration in the form of injection when described pharmaceutical composition
The content of compound shown in formula a and formula b or its pharmaceutically acceptable salt is each independently the 0.01 weight % of weight %~20.0,
Preferably 0.1 weight %-5.0 weight %.
In certain embodiments, described pharmaceutical composition or cosmetic composition are with once a day, twice daily, daily
Three times, five frequencies are administered four times per day or daily.
In above-mentioned all embodiments, the pharmaceutically acceptable salt is selected from alkali metal salt or alkali salt；Hydrogen halogen
Hydrochlorate；Inorganic acid salt；Acylate；And amino-acid salt.
The example of the alkali metal salt or alkali salt that can be used in the application includes but is not limited to sodium salt, sylvite and calcium
Salt.
Can be used in the halogen acid salt of the application example include but is not limited to hydrofluoride, hydrochloride, hydrobromate and
Hydriodate.
The example that can be used in the inorganic acid salt of the application includes but is not limited to nitrate, perchlorate, sulfate and phosphorus
Hydrochlorate.
Can be used in the acylate of the application example include but is not limited to mesylate, fumarate, succinate,
Citrate, tartrate, oxalates and maleate.
The example that can be used in the amino-acid salt of the application includes but is not limited to glutamate and aspartate.
In certain embodiments, the drug of the application or pharmaceutical composition include pharmaceutically acceptable surfactant,
Carrier, diluent, excipient, smoothing preparation, suspending agent, lubricant, film forming matter, coating aids or combinations thereof and formula a or formula
Compound shown in b or its pharmaceutically acceptable salt.Can be provided in drug or pharmaceutical composition preservative, stabilizer, dyestuff,
Corrigent, colorant, antioxidant, sweetener, aromatic, fragrance etc..It may include cosmetic field in cosmetic composition
In acceptable common medium, carrier or auxiliary agent, including but not limited to solvent, preservative, stabilizer, antioxidant and surface
Activating agent etc..
The drug and pharmaceutical composition of the application can produce according to known methods, for example, passing through conventional mixing, molten
The operating methods such as solution, granulation, manufacture pastille, grinding, emulsification, packing, retention or tabletting are produced.The cosmetic group of the application
Closing object can also be produced by method known in cosmetic field.
The application Chinese style a and formula b compound represented side effect are minimum, and biological safety and bioavilability are good, therefore
It is very suitable for clinical application.
Hereinafter, the disclosure passes through following examples with reference to the accompanying drawings and is explained in detail to more fully understand the disclosure
Various aspects and its advantage.It is simply used for illustrating the present invention it will be appreciated, however, that embodiment below is non-limiting
Certain embodiments.
Embodiment
Embodiment 1: animal wound Healing Experiments
Male guinea pig 12 of SPF rank similar in 5~6 week old, weight are selected, are divided into two groups, every group 6.In animal
Adaptive feeding starts to test after a week in room.Select area for 3 × 3cm in the back two sides apart from vertebra 1cm2Two it is right
Claim region to lose hair or feathers, and is shaved with doctor blade.After Animal Anesthesia, animal is transferred to the good ultra-clean work of ultraviolet sterilization
Make in platform, first hair-fields gone to be scrubbed with partial temperature sterile water, then wiped with Iodophor, finally with 75% alcohol disinfecting.With disappearing
The annular skin punch that poison is crossed manufactures round full thickness skin and cuts off trauma model, sterilizing bandaging after operation.The back of every animal
Portion includes a check plot, an administration area.The every cage list of the animal performed the operation only is raised, it is fasting for solids and liquids overnight, in second day
Just give standard feed and drinking-water.Administration group instills wound with the ethanol solution that the benzyl isothiocyanate or raphanin of 15mM are prepared
Area, check plot are instilled with the ethanol solution to sterilize, every 25 μ l/ times/day.After the production of skin excision trauma model, see every other day
The metamorphosis of wound is examined, while observing and measuring the wound area of animal in 2,4,6,8,10,11,12 days.This experiment uses number
Code camera combined calculation machine software analytic approach measures wound area.Wound healing rate: (initial area-is calculated according to following formula
Revolution mark)/initial area × 100%.Each wound duplicate measurements three times, average value as final wound area, and
Wound healing rate is calculated, 1, table 2 is shown in Table.
The effect experiment of 1. benzyl isothiocyanate of table (BITC) promotion skin wound healing.
| Test number of days | 2d | 4d | 6d | 8d | 10d | 11d |
| Control group healing rate (%) | 0 | 5 | 9 | 12 | 23 | 35 |
| Administration group healing rate (%) | 8 | 21 | 38 | 53 | 69 | 87 |
The effect experiment of 2. raphanin of table (SFE) promotion skin wound healing.
| Test number of days | 2d | 4d | 6d | 8d | 10d | 11d |
| Control group healing rate (%) | 0 | 5 | 9 | 12 | 23 | 35 |
| Administration group healing rate (%) | 15 | 37 | 50 | 61 | 77 | 93 |
From result as it can be seen that the wound healing rate of benzyl isothiocyanate and raphanin administration group will be apparently higher than control group, this
Show that both benzyl isothiocyanate and raphanin all have very good healing effect for wound.
Embodiment 2: wound skin histology HE slicing experiment
In embodiment 1, the 8th day when the skin histology of animal skin wound is cut, be put into 4% paraformaldehyde fixed
About for 24 hours, it is subsequently placed in dimethylbenzene, transparent 20 minutes, and is repeated 1 times.Then skin histology is placed in atoleine, 60
Wax 1 hour thoroughly in DEG C baking oven, it is repeated 3 times.Skin histology is embedded using paraffin wax embedding, and carries out paraffin using paraffin slicing machine
Slice, slice thickness are 5 μm, and then slice is put into hematoxylin dye liquor, dyes 4 minutes and encapsulates.Finally utilize microscope
Observation is sliced and takes pictures, and as a result sees Fig. 2.(the black in figure from figure 2 it can be seen that collagenous fibres in raphanin (SFE) administration group
Silk ribbon shape) content obviously increase, arrangement of collagen fibers rule, skin tissue morphology tends to restore normal.In contrast, it compares
Collagen contents in group are lower, and skin tissue morphology is abnormal.The above result shows that healing of the raphanin to skin wound
There is apparent facilitation.
Embodiment 3: the safety experiment of the liquid gel dressing of local administration
The skin of rabbit is very sensitive to irritative response, similar to the dermoreaction of people, can with judge drug locally to
Safety and irritating experimental model when medicine.This experiment is intended to the liquid gel dressing of observation the compounds of this invention preparation
To the toxic side effect and irritative response of the intact skin of new zealand rabbit when local administration.Specific experimental procedure is as follows:
(1) weigh 0.5 gram of benzyl isothiocyanate, 0.5 gram of raphanin, 4 grams of Sodium Hyaluronates and 0.5 gram of carbomer (viscosity:
940).Benzyl isothiocyanate or raphanin and Sodium Hyaluronate and carbomer are added in 90ml distilled water when quickly stirring,
Stirring is until Sodium Hyaluronate and carbomer all dissolve.10ml distilled water is separately supplied to 100ml, then stirs evenly gelled, is filled
Dress, irradiation sterilization.The dressing of benzyl isothiocyanate liquid gel and raphanin liquid gel dressing are obtained respectively；
(2) healthy new zealand rabbit 12 (SPF rank), weight (2.5 ± 0.2) kg.Experimental temperature is 18 DEG C~20 DEG C.Point
It is two groups, every group 6, every animal sub-cage rearing；
(3) new zealand rabbit backbone two sides are lost hair or feathers for 24 hours before administration, go gross area be body surface area 10% (about
120cm2), check whether skin of unhairing is injured due to unhairing, and injured skin should not make the stimulation of intact skin after unhairing for 24 hours
Property experiment；
(4) it is blank district that every rabbit left of spine, which goes to hair-fields, and right side is administration area.Daily every rabbit smears different sulphur cyanogen
The dressing of acid benzyl ester liquid gel or the dressing of raphanin liquid gel 1 time, it is continuous to smear 2 weeks, it is observed again after drug withdrawal 1 week.Except observation
And record outside daily erythema and oedema situation, also observation smears whether position has the feelings such as pigmentation, blutpunkte, pachylosis
Condition；
(5) when recorded observation, the dressing of benzyl isothiocyanate liquid gel and raphanin liquid gel dressing local administration
To new zealand rabbit without apparent toxic effect, to intact skin without any irritative response, it was demonstrated that different involved in the application
The safe coefficient of benzyl thiocyanate and raphanin is higher.
From the foregoing it is appreciated that although the purpose for exemplary illustration describes specific embodiments of the present invention,
But under condit without departing from the spirit and scope of the present invention, technical staff described in this field can make various modifications or change
Into.These deformations or modification should all fall into the application scope of the appended claims.
Claims (48)
1. drug or cosmetic that formula a or formula b compound represented or its pharmaceutically acceptable salt promote wound healing in preparation
Purposes in composition, wherein the wound is skin injury:
2. purposes as described in claim 1, wherein the drug and cosmetic composition are used for local application.
3. purposes as claimed in claim 2, wherein the drug and cosmetic composition with ointment, cream, emplastrum,
Paste, gelling agent, lotion, liniment, emulsion, solution, suspension, powder, granule, patch, paint, dressing, sponginum, spray
Mist agent and/or aerosol form are used for local application.
4. purposes as described in claim 1, wherein the drug is for being administered orally.
5. purposes as claimed in claim 4, wherein the drug is with tablet, capsule, emulsion, solution, suspension, powder
Or granular form is administered orally.
6. purposes as claimed in claim 2, wherein in the drug and cosmetic composition, shown in the formula a and formula b
The amount of compound or its pharmaceutically acceptable salt is each independently the 0.1 weight weight of %~10.0 %.
7. purposes as claimed in claim 6, wherein in the drug and cosmetic composition, shown in the formula a and formula b
The amount of compound or its pharmaceutically acceptable salt is each independently the 0.1 weight weight of %~5.0 %.
8. purposes as claimed in claim 7, wherein in the drug and cosmetic composition, shown in the formula a and formula b
The amount of compound or its pharmaceutically acceptable salt is each independently 0.5 weight %-3.0 weight %.
9. purposes as claimed in claim 4, wherein in the drug, the formula a and formula b compound represented or its drug
The amount of acceptable salt is each independently 0.01 weight %-20 weight %.
10. purposes as claimed in claim 9, wherein in the drug, the formula a and formula b compound represented or its medicine
The amount of the acceptable salt of object is each independently 0.1 weight %-10 weight %.
11. purposes as claimed in claim 10, wherein in the drug, the formula a and formula b compound represented or its medicine
The amount of the acceptable salt of object is each independently 0.1 weight %-5.0 weight %.
12. purposes as described in claim 1, wherein the drug is used for Formulations for systemic administration.
13. purposes as claimed in claim 12, wherein the Formulations for systemic administration is intravascular injection administration.
14. purposes as claimed in claim 13, wherein intravascular injection administration is selected from intravascular dropleting medicine-feeding, intravascular
Administered by infusion and intravascular bolus administration.
15. purposes as claimed in claim 13, wherein intravascular injection administration is the intravascular injection in the form of injection
Administration.
16. purposes as claimed in claim 12, wherein in the drug, compound or its drug shown in the formula a and formula b
The amount of acceptable salt is each independently 0.01 weight of weight %~20.0 %.
17. purposes as claimed in claim 16, wherein in the drug, compound or its drug shown in the formula a and formula b
The amount of acceptable salt is each independently 0.1 weight %-5.0 weight %.
18. the purposes as described in any claim in claim 1 to 17, wherein the wound be selected from trauma wounds, burn,
Sunburn, surgical wound, bedsore and diabetic ulcer wound.
19. the purposes as described in any claim in claim 1 to 17, wherein the drug or cosmetic composition are with every
Five frequencies are administered once, twice daily, three times a day, four times per day or daily for it.
20. purposes as claimed in claim 18, wherein the drug or cosmetic composition with once a day, twice daily,
Three times a day, five frequencies are administered four times per day or daily.
21. the purposes as described in any claim in claim 1 to 17, wherein the pharmaceutically acceptable salt is selected from alkali gold
Belong to salt or alkali salt, inorganic acid salt, acylate and amino-acid salt.
22. purposes as claimed in claim 21, wherein the alkali metal salt is sodium salt or sylvite.
23. purposes as claimed in claim 21, wherein the alkali salt is calcium salt.
24. purposes as claimed in claim 21, wherein the inorganic acid salt is selected from halogen acid salt, nitrate, perchlorate, sulphur
Hydrochlorate and phosphate.
25. purposes as claimed in claim 24, wherein the halogen acid salt be selected from hydrofluoride, hydrochloride, hydrobromate and
Hydriodate.
26. purposes as claimed in claim 21, wherein the acylate be selected from mesylate, fumarate, succinate,
Citrate, tartrate, oxalates and maleate.
27. purposes as claimed in claim 21, wherein the amino-acid salt is selected from glutamate and aspartate.
28. purposes as claimed in claim 18, wherein the pharmaceutically acceptable salt be selected from alkali metal salt or alkali salt,
Inorganic acid salt, acylate and amino-acid salt.
29. purposes as claimed in claim 28, wherein the alkali metal salt is sodium salt or sylvite.
30. purposes as claimed in claim 28, wherein the alkali salt is calcium salt.
31. purposes as claimed in claim 28, wherein the inorganic acid salt is selected from halogen acid salt, nitrate, perchlorate, sulphur
Hydrochlorate and phosphate.
32. purposes as claimed in claim 31, wherein the halogen acid salt be selected from hydrofluoride, hydrochloride, hydrobromate and
Hydriodate.
33. purposes as claimed in claim 28, wherein the acylate be selected from mesylate, fumarate, succinate,
Citrate, tartrate, oxalates and maleate.
34. purposes as claimed in claim 28, wherein the amino-acid salt is selected from glutamate and aspartate.
35. purposes as claimed in claim 19, wherein the pharmaceutically acceptable salt be selected from alkali metal salt or alkali salt,
Inorganic acid salt, acylate and amino-acid salt.
36. purposes as claimed in claim 35, wherein the alkali metal salt is sodium salt or sylvite.
37. purposes as claimed in claim 35, wherein the alkali salt is calcium salt.
38. purposes as claimed in claim 35, wherein the inorganic acid salt is selected from halogen acid salt, nitrate, perchlorate, sulphur
Hydrochlorate and phosphate.
39. purposes as claimed in claim 38, wherein the halogen acid salt be selected from hydrofluoride, hydrochloride, hydrobromate and
Hydriodate.
40. purposes as claimed in claim 35, wherein the acylate be selected from mesylate, fumarate, succinate,
Citrate, tartrate, oxalates and maleate.
41. purposes as claimed in claim 35, wherein the amino-acid salt is selected from glutamate and aspartate.
42. purposes as claimed in claim 20, wherein the pharmaceutically acceptable salt be selected from alkali metal salt or alkali salt,
Inorganic acid salt, acylate and amino-acid salt.
43. purposes as claimed in claim 42, wherein the alkali metal salt is sodium salt or sylvite.
44. purposes as claimed in claim 42, wherein the alkali salt is calcium salt.
45. purposes as claimed in claim 42, wherein the inorganic acid salt is selected from halogen acid salt, nitrate, perchlorate, sulphur
Hydrochlorate and phosphate.
46. purposes as claimed in claim 45, wherein the halogen acid salt be selected from hydrofluoride, hydrochloride, hydrobromate and
Hydriodate.
47. purposes as claimed in claim 42, wherein the acylate be selected from mesylate, fumarate, succinate,
Citrate, tartrate, oxalates and maleate.
48. purposes as claimed in claim 42, wherein the amino-acid salt is selected from glutamate and aspartate.
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| CN201510325412.7A CN106265112B (en) | 2015-06-12 | 2015-06-12 | Promote the drug or cosmetic composition of wound healing |
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| CN201510325412.7A CN106265112B (en) | 2015-06-12 | 2015-06-12 | Promote the drug or cosmetic composition of wound healing |
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| CN106265112B true CN106265112B (en) | 2019-05-31 |
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| WO2008122038A1 (en) * | 2007-04-02 | 2008-10-09 | President And Fellows Of Harvard College | Regulating autophagy |
| CN101780066B (en) * | 2010-01-29 | 2012-06-27 | 天津医科大学总医院 | Usage of isothiocyanate in preparing medicine for preventing from tumor invasion and metastasis |
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