CN107308145A - Insoral as skin anti-inflammatory preparation purposes - Google Patents

Insoral as skin anti-inflammatory preparation purposes Download PDF

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Publication number
CN107308145A
CN107308145A CN201710571206.3A CN201710571206A CN107308145A CN 107308145 A CN107308145 A CN 107308145A CN 201710571206 A CN201710571206 A CN 201710571206A CN 107308145 A CN107308145 A CN 107308145A
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insoral
skin
inflammatory
pharmaceutical composition
tnf
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CN107308145B (en
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吴训伟
李丁洋
周倩
郭泾
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Shandong University
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Shandong University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/155Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses purposes of the insoral as skin anti-inflammatory preparation.Present invention firstly discovers that insoral, which can significantly inhibit skin epidermal cells secretion inflammation cell factor, includes interleukin 6/8 (IL 6, IL 8) and TNF (TNF α), and can equally significantly decrease the conventional acetate of 12 oxygen Tetradecanoylphorbol 13 (TPA) and polyinosinic acid polyinosinic polycytidylic acid (poly I:C) the application on human skin epithelial cell inflammatory reaction of (immunostimulant) induction, therefore can be used for preventing and treating scytitis relevant disease.So as to open new application for insoral, new prevention and treatment means are provided for scytitis relevant disease.

Description

Insoral as skin anti-inflammatory preparation purposes
Technical field
The invention belongs to medical pharmaceutical field, and in particular to a kind of insoral as skin anti-inflammatory preparation purposes.
Background technology
Dermatitis (Dermatitis) refers to the dermal inflammatory disease caused by various inside and outside portion's infection or non-infectious factor The general term suffered from, a not independent disease, its cause of disease and complicated clinical manifestation are various, and recurrent exerbation, and clinical treatment is more It is difficult.Modern medicine study thinks that the dermatitis illness cause of disease is sufficiently complex, may be relevant with following factors:Including internal factor (such as menstruation is disorderly for such as chronic infection focus (such as chronic cholecystitis, tonsillitis, intestinal parasitic disease), endocrine and metabolism change Unrest, gestation etc.), blood circulation disorder (such as shank vein varicose), psychoneural factor, inherent cause;External factor is as eaten Thing (such as fishes and shrimps, beef and mutton), inhalation (inhalatio) (such as pollen, dust mite), living environment (such as hot and cold, dry), animal skin, Various physics and chemistry materials (such as cosmetics, soap, synthetic fibers).Current treatment policy is for the cause of disease or various suspicious pathogenic Factor is treated, the positive infection control of infective inflammation, and the general principle of reatment of non-infectious inflammation is treated for systemic drug, is resisted It is scorching, antipruritic.
With the development of the association areas such as molecular biology, it has been found that generation, development and the interferon of dermatitis, inflammation are thin Closely related, such as Guo Yan (Chen Yan, Guo such as intracellular cytokine, TNF (TNF α), Fas associated deaths domain (FADD) albumen In training, CHENYan waits comparative studies of the antihistamines of new generation to 3 kinds of cytokine influences of allergic contact dermatitis mouse [J] clinic skins section magazine, 2006,35 (1):6-8) research Mizolastine, Loratadine and cetirizine are contacted to allergia Property dermatitis (allergiccontact dermatitis, ACD) mouse produce interferon (IFN), TNF (TNF α) And the influence of interleukin (IL) -4, inquire into the mechanism of action that antihistamine treats ACD;Bonnet etc. (Bonnet M C, Preukschat D,Welz P S,et al.The Adaptor Protein FADD Protects
Epidermal Keratinocytes from Necroptosis In Vivo and Prevents Skin Inflammation[J].
Immunity,2011,35(4):572-582) etc. research is pointed out to show with the mouse that FADD epithelial properties melt The necroptosis of spontaneous horn cell, and serious inflammatory skin damaged is formed in several days in birth, therefore FADD is at angle To maintaining the balance between cutaneous immunisation reaction and prevention scytitis most important in cell plastid.Therefore research acts on above-mentioned The influence material of protein factor turns into an important directions of research and development prevention and treatment dermatitis relevant disease.
Insoral (Phenformin) is a kind of for treating adult's Non-Insulin Dependent Diabetes Mellitus and part pancreas islet The common medicine of plain dependent diabetes.Its effect reduces liver production to promote intake and glycolysis of the muscle cell to glucose Give birth to glucose and play anti-high-blood-sugar function, can be shared with insulin, be relatively easy to control blood glucose, insulin dosage can be reduced.To obesity Patients with type Ⅰ DM person, is still lost weight using its appetite-suppressing and intestinal absorption glucose.Because it has larger probability to induce sugar Patient's having diabetes complication --- lactic acidosis is urinated, on November 18th, 2016, state food pharmaceuticals administration is total Office issues《The bulletin of insoral is used on stopping production and sales》.
The content of the invention
For above-mentioned the deficiencies in the prior art, inventor passes through long-term technology and practical exploration, has been surprisingly found that benzene second is double Guanidine, which can significantly inhibit skin epidermal cells secretion inflammation cell factor, includes interleukin 6/8 (IL-6, IL-8) and tumour Necrosin (TNF α), and can equally significantly decrease conventional 12- oxygen-Tetradecanoylphorbol -13- acetates (TPA) With polyinosinic acid polyinosinic-polycytidylic acid (poly I:C) the application on human skin of (immunostimulant) induction Epithelial cell inflammatory reaction, consequently found that there is insoral anti-scytitis to act on, can development and application in clinic for pre- Anti- and treatment scytitis relevant disease.
Specifically, the present invention relates to following technical scheme:
One aspect of the present invention, discloses insoral as the purposes of skin anti-inflammatory preparation, and therefore, for prevention And/or the treatment disease related to dermatitis (scytitis) is extremely effective;
Another aspect of the present invention, disclosing insoral as skin anti-inflammatory preparation is used to prepare prevention and/or controls Treat the purposes of the medicine of scytitis relevant disease;
According to the present invention, the representation of concept of " prevention and/or treatment " is any to be applied to treat scytitis relevant disease Measure, either the disease for this performance or the symptom showed carry out prophylactic treatment or avoid this disease Recurrence, the symptom of such as recurrence after treatment time section is finished or disease to having broken out treats.
In the sense of the present invention, " skin anti-inflammatory preparation " represents a kind of material, and it hinders, delays or suppress and dermatitis Disease related inflammatory cytokine, TNF and/or immunostimulant;
Wherein, the inflammatory cytokine includes but is not limited to interleukin 6/8 (IL-6, IL-8);
The TNF includes but is not limited to TNF α/TNF β;
The immunostimulant includes but is not limited to 12- oxygen-Tetradecanoylphorbol -13- acetates (TPA)/poly IC Thuja acid polyinosinic-polycytidylic acid (poly I:C);
According to the understanding of the present invention, the concept of " suppressions " it will be appreciated that with not using the inflammatory cytokine of insoral, TNF and/or immunostimulant are compared, the work of inflammatory cytokine, TNF and/or immunostimulant Property slack-off (delaying) and/or reduction, preferably reduction up to 10%, also, it is preferred that up to 40%, more preferably up to 60%, it is preferably high Up to 70%, also, it is preferred that up to 80%, more preferably up to about 90%, equally more preferably up to 95%, and more preferably up to 98%, Most preferably 100%.
Another aspect of the present invention, discloses scytitis relevant disease and includes but is not limited to erythema, skin spinous layer Loosen, the burning sensation in pemphigus, eczema, leucoderma, lichen planus, contact dermatitis, atopic dermatitis, inflammatory process, thorn Pain and/or scratchiness, skin ulcer, acne;
For the effective prevention and/or treatment of scytitis relevant disease, it is particularly possible to by applying insoral medicine Active component, in the case where considering form of medication, they preferably have lower Column Properties:
A) in local application skin anti-inflammatory preparation of the present invention:To the local administration by any long period and effectively into The dynamic (dynamical) local applicability (correspondingly applying to parenterai administration) of high transdermal delivery divided;
B) active ingredient is significantly uniformly distributed in the range of application point and avoids local concentration too high;
C) preferably it is enriched with involved body part, as far as possible with postponing to blood circulation (i.e. endovascular conveying) It is combined;
D) inhibitory action, i.e., in involved body part to the related inflammatory cytokine of scytitis, neoplasm necrosis The obstruction or inhibitory action of the factor and/or immunostimulant activity;
Simultaneously, it is necessary to it is emphasized that be used to treat the related disease of scytitis as active ingredient using insoral Disease has the characteristics that:
1) possibility of the local application insoral on skin is passed through so that reach and be enough in epiderm skin or intradermal The insoral concentration of therapeutic effect is realized, other organs during without as Formulations for systemic administration in body reach similar high benzene second Biguanide concentration;And there is no strong side effect to the skin histology of other organs or health;
2) coherent condition of insoral can be liquid, gaseous state or solid-state during local administration.Can be with to the conveying of skin By insoral either by the preparation and direct skin contact containing insoral or through middle layer such as air, micropore Film etc. spreads to realize;
According to the present invention, insoral is not only disclosed as the effect as skin anti-inflammatory preparation, and is also disclosed, Using insoral and other at least one active constituents of medicine combination when, this effect can be strengthened.It is used as other medicines The replacement or supplement of active component, insoral can also be used with other non-drug active ingredient combinations.
In view of this, another aspect of the present invention, disclose insoral and at least one other active constituents of medicine and/ Or the pharmaceutical composition that at least one other non-drug active component is constituted.
Wherein, other medicines active component can be used for prevention and/or/treatment to include but is not limited to erythema, skin spinous layer Loosen, the burning sensation in pemphigus, eczema, leucoderma, lichen planus, contact dermatitis, atopic dermatitis, inflammatory process, thorn Pain and/or scratchiness, skin ulcer, acne;
Other non-drug active components include pharmaceutically acceptable carrier, excipient and/or diluent.For example pharmaceutically Compatible inorganic or organic acid or alkali, polymer, copolymer, block copolymer, monose, polysaccharide, ion and non-ionic surface Activating agent or lipid, pharmacologically harmless salt such as sodium chloride, flavor enhancement, vitamin such as vitamin A or vitamin E, fertility Similar vitamin or provitamin, antioxidant present in phenol or human biological object, such as ascorbic acid, and for prolonging The use of long active constituents of medicine or formula and the stabilizer and/or preservative of holding time, and it is other known in the prior art Conventional non-drug active component or auxiliary agent and additive, and their mixture.It is other according to currently preferred non-medicine Especially all materials that may be constructed hydrogel of thing active component, such as natural or synthetic can form the solvable of mesh In the polymer of water.
In accordance with the purpose of the invention, the administration of described pharmaceutical composition can be via perfusion, via endoscope, or conduct Aerosol or dry powder formulations and local, transdermal, nasal cavity, enteron aisle, non-bowel are implemented.The specific formulation bag of described pharmaceutical composition Include oral formulations, injection, spray, creme, paste, lotion, emulsion, gel or hydrogel.
Wherein, administering mode is preferably part and cutaneous penetration, by applying described pharmaceutical composition on skin come real Apply, preferably the liquid containing insoral, gas (aerosol or steam), preparation, preferably as creme, paste, lotion, emulsion, Or gel or hydrogel are implemented.
It is extremely to have to the scytitis relevant disease according to currently preferred part or cutaneous penetration insoral Profit.Can be in the high therapeutically effective insoral of the local application of skin according to currently preferred part or cutaneous penetration Concentration, at the same can reduce or avoid completely system (blood circulation) load and to the healthy skin tissue that need not treat with And the side effect of the tissue of other organs.
Simultaneously, it is possible to use means commonly known in the art suppress or limitation insoral is from Skin Cell to whole body Transport.The example of this means is mainly targetedly manipulated via skin (i.e. between body part and skin surface) Osmotic gradient, the flow of water, the material are reduced by using the material of the flow of water of suitable change local application insoral Can be the salt of physiological compatible, such as sodium chloride, water-soluble polymer and other non-pharmaceutical materials.
Beneficial effects of the present invention:Present invention firstly discovers that insoral, which can significantly inhibit skin epidermal cells, secretes a variety of Inflammatory cytokine includes interleukin 6/8 (IL-6, IL-8) and TNF (TNF α), and equally can significantly drop Low conventional 12- oxygen-Tetradecanoylphorbol -13- acetates (TPA) and polyinosinic acid polyinosinic- polycytidylic acid(poly I:C) the application on human skin epithelial cell inflammatory reaction of (immunostimulant) induction, therefore can be with For preventing and treating scytitis relevant disease.It is the related disease of scytitis so as to open new application for insoral Disease provides new prevention and treatment means.
Brief description of the drawings
Fig. 1 is the various inflammatory cytokine (IL- of suppression epidermal cell in various concentrations insoral in vitro cell culture 6, IL-8, TNF α) expression block diagram;
Fig. 2 is human skin cell's inflammatory Cytokines Expression block diagram that insoral suppresses TPA inductions;
Fig. 3 is that insoral suppresses immunostimulant Poly I:The various inflammatory cytokines of human skin cell of C inductions (IL-6, IL-8, TNF α) expresses block diagram;
Fig. 4 is the inflammatory reaction that insoral handles reduction TPA inducing mouse ears;Wherein, Fig. 4 A. are different disposal bar Mouse ear histopathology schematic diagram under part, Fig. 4 B are mouse ear Thickness Analysis block diagram under the conditions of different disposal.
Embodiment
It is noted that described further below is all exemplary, it is intended to provide further instruction to the application.Unless another Indicate, all technologies used herein and scientific terminology are with usual with the application person of an ordinary skill in the technical field The identical meanings of understanding.
It should be noted that term used herein above is merely to describe embodiment, and be not intended to restricted root According to the illustrative embodiments of the application.As used herein, unless the context clearly indicates otherwise, otherwise singulative It is also intended to include plural form, additionally, it should be understood that, when in this manual using term "comprising" and/or " bag Include " when, it indicates existing characteristics, step, operation, device, component and/or combinations thereof.
Term is explained:In the sense of the present invention,
Paste is the pharmaceutical preparation of external application, is made up of lubricating substance matrix (such as vaseline), such as by mixing to it It is middle to add real medicinal pharmacy and/or non-drug active component;
Creme be can additionally comprise other constituents according to the present invention paste, for example it is used for cosmetic activity into Point, such as flavouring agent, pigment and/or emulsifying agent, such as lecithin.Creme should generally be different from emulsion, and most of this difference takes Certainly in prepared viscosity grade.According to the present invention, creme also is understood as emulsion.
Emulsion is big milk or microemulsion thing, based on water-in-oil type or oil-in-water type.
Gel be macromolecular substances solution, such as agarose, acrylic acid, alginic acid, polysiloxanes or acrylamide, its Concentration is so high, (such as salt, acid, is filled out so that the macromolecular dissolved adds other materials in appropriate combination and optionally Material, buffer substance) under conditions of be combined into spongy, three-dimensional construction, there is fluid in its cavity.Thus gel has relative Fixed concentration.Viscosity is between liquid and solid-state.
Hydrogel represents a kind of gel, it is characterized in that to the high absorptive capacity of water, in the sense of the present invention preferably its 20 It is made up of to 99%, more preferably 70 to 99%, and particularly preferred 80 to 99% water, but does not show what typical fluid had Rheological behavior.In an especially preferred embodiment, the hydrogel is transparent, permeability while being easy to apply Smear, without having influence on its form and integrality due to smearing gel.
It should be noted that above-mentioned paste, creme, emulsion, milk or gel or hydrogel are according to any existing skill Known standard method is carried out in art.The concentration that these methods and component to be used or material should be selected is to professional and technical personnel It is known.
As background technology is introduced, not yet find that insoral can be used in preventing and treating scytitis phase so far Related disorders;
In view of this, in a kind of embodiment of the invention, insoral is disclosed as skin anti-inflammatory preparation Purposes, and therefore, for preventing and/or treating the disease related to dermatitis (scytitis) extremely effective;
In the still another embodiment of the present invention, disclose insoral is used to prepare prevention as skin anti-inflammatory preparation And/or the purposes of the medicine for the treatment of scytitis relevant disease;
Wherein, " skin anti-inflammatory preparation " represents a kind of material, and it hinders, delays or suppress the inflammation related to scytitis Cell factor, TNF and/or immunostimulant;
Wherein, the inflammatory cytokine includes but is not limited to interleukin-6/8 (IL-6, IL-8);
The TNF includes but is not limited to TNF α/TNF β;
The immunostimulant includes but is not limited to 12- oxygen-Tetradecanoylphorbol -13- acetates (TPA)/poly IC Thuja acid polyinosinic-polycytidylic acid (poly I:C);
In the still another embodiment of the present invention, disclosing scytitis relevant disease, to include but is not limited to skin red In spot, acantholysis, pemphigus, eczema, leucoderma, lichen planus, contact dermatitis, atopic dermatitis, inflammatory process Burning sensation, tingling sensation and/or scratchiness, skin ulcer, acne;
In the still another embodiment of the present invention, disclose in accordance with the purpose of the invention, insoral and at least one The pharmaceutical composition that other medicines active component and/or at least one other non-drug active component are constituted.
Wherein, other medicines active component can be used for prevention and/or/treatment to include but is not limited to erythema, skin spinous layer Loosen, the burning sensation in pemphigus, eczema, leucoderma, lichen planus, contact dermatitis, atopic dermatitis, inflammatory process, thorn Pain and/or scratchiness, skin ulcer, acne;
Other non-drug active components include pharmaceutically acceptable carrier, excipient and/or diluent.For example pharmaceutically Compatible inorganic or organic acid or alkali, polymer, copolymer, block copolymer, monose, polysaccharide, ion and non-ionic surface Activating agent or lipid, pharmacologically harmless salt such as sodium chloride, flavor enhancement, vitamin such as vitamin A or vitamin E, fertility Similar vitamin or provitamin, antioxidant present in phenol or human biological object, such as ascorbic acid, and for prolonging The use of long active constituents of medicine or formula and the stabilizer and/or preservative of holding time, and it is other known in the prior art Conventional non-drug active component or auxiliary agent and additive, and their mixture.It is other according to currently preferred non-medicine Especially all materials that may be constructed hydrogel of thing active component, such as natural or synthetic can form the solvable of mesh In the polymer of water.
In the still another embodiment of the present invention, in accordance with the purpose of the invention, the administration of described pharmaceutical composition can be with Via perfusion, via endoscope, or as aerosol or dry powder formulations, local, transdermal, nasal cavity, enteron aisle, non-bowel are come Implement.The specific formulation of described pharmaceutical composition includes oral formulations, injection, spray, creme, paste, lotion, emulsion, solidifying Glue or hydrogel.
Wherein, administering mode is preferably part and cutaneous penetration, by applying described pharmaceutical composition on skin come real Apply, preferably the liquid containing insoral, gas (aerosol or steam), preparation, preferably as creme, paste, lotion, emulsion, Or gel or hydrogel are implemented.
It should be noted that insoral may induce lactic acidosis in treatment diabetic, (incidence of disease is about In 6/10000ths (0.06%)), up to the present also Wei You local applications cause the report of lactic acidosis.Thus the present invention is carried Go out local topical insoral and can be prevented effectively from effective ingredient to act on body other parts, it is relatively safe.But go out In security consideration, before extensive its security of case verification experimental verification is not carried out, it is not recommended that the sugar with dermatitis relevant disease Urine patient uses.
Explanation is further explained to the present invention by the following examples, but is not construed as limiting the invention.
Embodiment
Materials and methods
1) the primary epidermal cell of people is separately cultured:
Sterilization in the PBS containing 2% mycillin was put into after tissue was pre-processed as 30 seconds in 70% ethanol, after Tissue is chopped into after homogenate and is transferred in the 50ml centrifuge tubes of the liquid containing enzymic digestion 37 ° of water-baths and shakes 1 hour, 0.25% is then added Trypsin Induced 30 minutes;The DMED culture mediums containing 10% hyclone for having added same volume after having digested are blown and beaten repeatedly After filter, 1000xg centrifuge 5 minutes, abandon supernatant, be repeated once, cell precipitation using epidermal cell culture base be resuspended after add Rock suppression Preparation Y27632 is cultivated.
2) insoral processing epidermal cell:
Take the epidermal cell (P3) of culture to be inoculated in six orifice plates, 2ml culture mediums are used per the cell of hole 300,000, inoculation 24 is small When after change culture medium, reuse various concentrations insoral (0,0.5mM/L, 1.0mM/L, 1.5mM/L) processing epidermal cell 24 hours.
3)TPA/Poly(I:C)+insoral processing epidermal cell:
Take the epidermal cell (P3) of culture to be inoculated in six orifice plates, 2ml culture mediums are used per the cell of hole 300,000, inoculation 24 is small When after change culture medium, then use 5ug/mlTPA, 5ug/ml Poly (I respectively:C) processing epidermal cell 2 hours, is then added Insoral (0,0.5mM/L, 1.0mM/L, 1.5mM/L) processing epidermal cell 22 hours.
4) cell is collected and carries RNA and protein:
RNA is extracted using TAKARA kits, and sample albumen is extracted using RIPA cracking process.
5) RT-PCR surveys inflammatory Cytokines Expression:
RNA samples, which are used, uses Real-time quantitative PCR detection to include IL6, IL8 after TAKARA kit reverse transcriptions, The expression of the inflammation factor and ATF-3 including TNF-α.
6) ELISA surveys inflammatory factor level:
Take cell culture supernatant:Sample is centrifuged 15 minutes in 4 ° of lower 1000xg, and it is Elisa experiment samples to take supernatant, IL-6, IL-8, TNF-α expression are detected using R&D systemsValukine kits.
7) insoral suppresses the inflammatory reaction of TPA inductions in vivo:
Mouse inflammatory model is set up in the induction inflammatory reaction of C57 mouse right ears within 2 hours, benzene second is then used afterwards using TPA Biguanides processing, plus Aceton is as a control group.Ear is collected after 24 hours and its thickness is measured, the group for observing ear is dyed by HE Knit structure and inflammatory cell intrusion.
Result of the test
1. as shown in figure 1, insoral suppresses the expression of skin epidermal cells inflammatory factor, and there is a dose-response relationship, In 0.5~1.5mM/L concentration ranges, insoral concentration is higher, and to IL-6, IL-8, the depression effect of TNF-α is more notable.
2. in vitro, insoral can effectively suppress application on human skin epidermal cell inflammatory reaction generation anti-inflammatory work caused by TPA With as shown in Fig. 2 insoral can effectively suppress human skin cell's inflammatory Cytokines Expression of TPA inductions, in 0.5~1.5mM/L In concentration range, insoral concentration is higher, and depression effect is more obvious;
3. in vitro, insoral can effectively suppress immunostimulant Poly I:Application on human skin epidermal cell inflammation caused by C Reaction produces antiinflammatory action, as shown in figure 3, insoral can effectively suppress human skin cell's inflammatory Cytokines Expression of TPA inductions, In 0.5~1.5mM/L concentration ranges, insoral concentration is higher, and depression effect is more obvious;
4. in animal (mouse) is tested (internal), insoral can equally eliminate the scytitis of TPA inductions in vivo Reaction, as shown in Figure 4 A, adds insoral and significantly reduces inflammatory reaction, and inflammatory cell invades profit;Fig. 4 B are that quantitative analysis is small The change of mouse ear thickness, *, which is represented, is not added with insoral and control (control) and (TPA+ for adding insoral Phenformin) there is conspicuousness difference (p<0.05).
From above-mentioned experiment, in vivo or in vitro, insoral can effectively suppress to include IL-6, IL-8, and TNF-α etc. exists The expression of the interior inflammation factor, and in the range of finite concentration, insoral concentration is higher, and its antiinflammatory action is stronger.Table The bright compound can as external preparation for skin anti-inflammatory drug.
The preferred embodiment of the application is the foregoing is only, the application is not limited to, for the skill of this area For art personnel, the application can have various modifications and variations.It is all within spirit herein and principle, made any repair Change, equivalent substitution, improvement etc., should be included within the protection domain of the application.

Claims (10)

1. insoral is used as the purposes of skin anti-inflammatory preparation.
2. purposes according to claim 1, it is characterised in that insoral is used to prepare as skin anti-inflammatory preparation to be prevented And/or the purposes of the medicine for the treatment of scytitis relevant disease.
3. purposes according to claim 1, it is characterised in that the skin anti-inflammatory preparation be used to hinder, delay or suppress and Scytitis related inflammatory cytokine, TNF and/or immunostimulant.
4. purposes according to claim 3, it is characterised in that wherein, the inflammatory cytokine includes interleukin-6, Bai Jie Element -8;
The TNF includes TNF α, TNF β;
The immunostimulant includes 12- oxygen-Tetradecanoylphorbol -13- acetates, polyinosinic acid.
5. purposes according to claim 2, it is characterised in that the scytitis relevant disease includes erythema, skin Calcination in acantholysis, pemphigus, eczema, leucoderma, lichen planus, contact dermatitis, atopic dermatitis, inflammatory process Sense, tingling sensation and/or scratchiness, skin ulcer, acne.
6. a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition contains insoral and at least one other medicine Active component and/or at least one other non-drug active component.
7. pharmaceutical composition as claimed in claim 6, it is characterised in that the other medicines active component be used to prevent and/or/ Treatment include but is not limited to erythema, acantholysis, pemphigus, eczema, leucoderma, lichen planus, contact dermatitis, Burning sensation, tingling sensation and/or scratchiness, skin ulcer, acne in atopic dermatitis, inflammatory process.
8. pharmaceutical composition as claimed in claim 6, it is characterised in that other non-drug active components include pharmaceutically may be used Carrier, excipient and/or the diluent of receiving.
9. pharmaceutical composition as claimed in claim 6, it is characterised in that the pharmaceutically acceptable carrier, excipient and/or The inorganic or organic acid or alkali of diluent including pharmaceutically compatible, polymer, copolymer, block copolymer, monose, polysaccharide, from Present in son and nonionic surface active agent or lipid, pharmacologically harmless salt, vitamin, tocopherol or human biological object Similar vitamin or provitamin, antioxidant, and stabilizer and/or preservative, and their mixture.
10. pharmaceutical composition as claimed in claim 6, it is characterised in that described pharmaceutical composition formulation includes oral formulations, note Penetrate agent, spray, creme, paste, lotion, emulsion, gel or hydrogel;It is preferred that, described pharmaceutical composition formulation be creme, Paste, lotion, emulsion, gel or hydrogel.
CN201710571206.3A 2017-07-13 2017-07-13 Application of phenformin in preparing anti-skin inflammation preparation Active CN107308145B (en)

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CN201710571206.3A CN107308145B (en) 2017-07-13 2017-07-13 Application of phenformin in preparing anti-skin inflammation preparation

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CN201710571206.3A CN107308145B (en) 2017-07-13 2017-07-13 Application of phenformin in preparing anti-skin inflammation preparation

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CN107308145B CN107308145B (en) 2021-03-16

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Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
H. RALPH SCHUMACHER等: "Erythema elevatum diutinum:Cutaneous Vasculitis, Impaired Clot Lysis, and Response to Phenformin", 《THE JOURNAL OF RHEUMATOLOGY》 *
R. LIM等: "Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators", 《PLACENTA》 *
张开明等主编: "《最新皮肤科学理论与实践》", 31 March 2001, 中国医药科技出版社 *

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