CN109966274A - Application of the guaiol in the drug that preparation inhibits tumour correlation M2 type macrophage - Google Patents

Abstract

The present invention relates to the new indication technical fields of drug, specifically, being application of the guaiol in the drug that preparation inhibits tumour correlation M2 type macrophage, the invention also discloses a kind of drugs for inhibiting tumour correlation M2 type macrophage.The present invention is found through experiments that, guaiol can modify M2 macrophage phenotype, promote M2 macrophage to the macrophages turn without induced activation, the expression of Macrophage Surface marker, the expression of the cell factor of macrophages secrete, the expression of M2 macrophage mRNA, expression of M2 macrophage protein etc. are significantly inhibited, pass through the inhibition to M2 macrophage, achieve the purpose that inhibit tumour growth, invasion and transfer, to realize the treatment to tumour.Guaiol provides new thinking as a kind of efficient antitumorigenic substance of low toxicity, for treatment tumour, has very big prospect in medicine.

Description

Application of the guaiol in the drug that preparation inhibits tumour correlation M2 type macrophage

Technical field

The present invention relates to the new indication technical fields of drug, specifically, being that guaiol is related in preparation inhibition tumour Application in the drug of M2 type macrophage.

Background technique

Tumour is to seriously threaten a kind of disease of human health.It and cardiovascular disease become the cause of death in the whole world Front two.In tumor tissues, contain more non-tumor cell, including stroma cell (fibroblast and endothelial cell) And leucocyte.Macrophage is the main component for the leucocyte that tumour is arrived in infiltration.Macrophage in tumor tissues, i.e. tumour phase It closes macrophage (Tumor-associatedmacrophage, TAM), is played with the relationship of tumour and in tumour a variety of Function is just by in-depth study.The different state of activation of tumor-associated macrophage determines that it is that performance is antitumor in tumour Effect or Tumor acceleration.On the one hand, it can be played by phagocytosis, killing tumor cell and submission tumor associated antigen immune Monitoring and antitumor action；On the other hand, tumour growth and blood can be promoted by discharging many chemotactic factor (CF)s and cell factor Pipe generates, and can promote invasion and metastasis of tumor with matrix degradation.

Macrophage is at least divided into two types: M1 type, i.e., the macrophage of classical activation (Classicallyactivated macrophage) and M2 type, i.e., the macrophage (Alternatively of alternative activation activated macrophage).M1 type macrophage produces under the induction of bacterium or its product lipopolysaccharides or interferon-γ It is raw, show themselves in that the ability of high present antigen；Hypersecretion interleukin 12 and interleukin 23 and its I type then induced Immune response is high: the ability of high yield toxigenicity intermediate product (nitric oxide, reactive oxygen intermediates).Therefore, M1 type macrophage is thin Born of the same parents are considered to have killing bacterium and tumour cell and the ability that can secrete a variety of pro-inflammatory cytokines.And M2 type macrophage is thin Born of the same parents can be produced by inductions such as interleukin-4, interleukin-13, glucocorticoid, transforming growth factor-β and prostaglandin E2s It is raw, show as the ability of low present antigen；It generates and inhibits cell Proliferation and active cell factor, such as interleukin 10； It is preferable to remove making every effort to promote for fragment；Into the ability of angiogenesis and wound healing.

In recent years more and more researches show that TAM does not play antitumor action, but take part in tumour generation, The process of growth, invasion and transfer, it is especially closely related with the angiogenesis of tumour and lymphatic vessel generation.According to macrophage The activation type of the effect and macrophage that are played in tumour, it is presumed that there is the macrophages of both types in tumour Cell, and the early stage of tumor development, the macrophage in tumour play immunosurveillance and antitumor work based on M1 type With；And advanced stage tumour, the macrophage in tumour plays the work for promoting tumour growth, invasion and transfer based on M2 type With；The change of type has occurred in tumour early stage and advanced tumor in macrophage in tumour, to influence the growth of tumour, invasion And transfer.

Guaiol is from guaiaci lignum, Radix Ophiopogonis, cortex cinnamomi, Cortex Magnoliae Officinalis, rhizoma atractylodis, Rhizoma Et Radix Notopterygii, rhizoma acori graminei, HERBA SIPHONOSTEGIAE, fructus amomi, Eucalyptus globules fruits A kind of fat-soluble native compound extracted in the plants such as reality, alpine yallow herb, Blumea balsamifera, azalea, asafoetide, propolis is a kind of times Hemiterpene alcohol, molecular formula C15H26O, molecular weight 222.37 are currently used primarily in perfume industry.

Chinese patent literature 201410032832.1 discloses a kind of medicinal usage of guaiol, and the purposes refers to more Wound alcohol is used to prepare treatment anti-tumor drug preparation as one of active constituent or sole active agent, and result of study shows: Guaiol can significantly inhibit activity of tumor cells and proliferation in vitro, but not inhibit the existence of normal immunocyte；Guaiol exists Tumour growth can obviously be inhibited in vivo；Therefore, guaiol is a kind of to be expected exploitation as the efficient anti-tumor medicinal preparation of low toxicity Active material has prospect in medicine.Chinese patent literature 201110133892.9 discloses guaiol and is preparing vegetable insecticide In purposes, as the result is shown through insecticidal test: guaiol to test worm show food refusal, tag, fumigate it is similar with juvenile hormone Object activity, the mode of action are closely related with dosage；Contact toxicity LD50 to 4 age mythimna separatas and 3 age diamondback moths is respectively 0.072mg/ head, for 24 hours with 8.920mg/ head, for 24 hours；Fumigation effect LC50 to housefly and 4 age mythimna separata adults is respectively 3.52 μ L/ L, 12h and 16.95 μ L/L, 12h, the results showed that, its insecticidal activity of the compound is preferable, it can be used as insecticidal active ingredient, Further prepare the vegetable insecticide of the types such as spray or fumigant.

But inhibiting the application in tumour correlation M2 type macrophage about guaiol, it yet there are no report.

Summary of the invention

The first purpose of this invention is aiming at the shortcomings in the prior art, to provide a kind of new application of guaiol.

Second object of the present invention is to provide a kind of drug for inhibiting tumour correlation M2 type macrophage.

To realize above-mentioned first purpose, the technical solution adopted by the present invention is that:

Application of the guaiol in the drug that preparation inhibits tumour correlation M2 type macrophage.

As an optimal technical scheme of the invention, the guaiol is as inhibition tumour correlation M2 type macrophage The drug of the sole active agent of drug or M2 type macrophage related to other inhibition tumours is collectively as active constituent.

It is highly preferred that the guaiol inhibits the application in the active drug of M2 type macrophage proliferation in preparation.

It is highly preferred that the guaiol promotes M2 type macrophage to turn to the macrophage without induced activation in preparation Application in the drug of change.

It is highly preferred that application of the guaiol in the drug that preparation inhibits M2 type Expression of Macrophages.

To realize above-mentioned second purpose, the technical solution adopted by the present invention is that:

A kind of drug inhibiting tumour correlation M2 type macrophage, the active constituent of the drug are guaiol.

As an optimal technical scheme of the invention, the drug for inhibiting tumour correlation M2 type macrophage further includes Pharmaceutically acceptable carrier.

As an optimal technical scheme of the invention, the pharmaceutically acceptable carrier includes emulsifier, figuration Agent, filler, adhesive, wetting agent, disintegrating agent, sorbefacient, flavoring agent, colorant or cosolvent.

As an optimal technical scheme of the invention, the dosage form of the drug is pulvis, granule, tablet, capsule Agent, pill, solution, suspension or injection.

" pharmaceutically acceptable " refers to not biologically or the substantially undesirable substance of other aspects, can be by institute Administering substances are stated in individual, without will lead to any substantially undesirable biotic influence or in harmful manner and comprising this Any component of the composition of substance interacts.

The substance that " carrier " is also referred to as " excipient " includes any commonly employed excipient in pharmacy, and should be based on compatible The release profile property of property and desired dosage form selects.Exemplary carrier substance includes, for example, emulsifier, adhesive, suspending Agent, disintegrating agent, filler, surfactant, solubilizer, stabilizer, lubricant, wetting agent, diluent etc.." pharmaceutically receive Carrier " may include, for example, Arabic gum, gelatin, colloidal silicon dioxide, calcium glycerophosphate, calcium lactate, dextrin-maltose are multiple Mixture, glycerol, magnesium silicate, casein sodium, soybean lecithin, sodium chloride, tricalcium phosphate, dipotassium hydrogen phosphate, stearoyl lactylates Sodium, carrageenan, monoglyceride, diglyceride, pregelatinized starch etc..

As an optimal technical scheme of the invention, drug of the invention or pharmaceutical composition are each of this field routine Kind of dosage form, the preferably form of solid, semisolid or liquid, can be aqueous solution, non-aqueous solution or suspension, more preferably Pulvis, granule, tablet, capsule, pill, solution, suspension or injection etc..The administration of the drug or pharmaceutical composition Approach is preferably drug administration by injection or oral administration.The drug administration by injection preferably includes intravenous injection, intramuscular injection, abdominal cavity note It penetrates, the approach such as intracutaneous injection or subcutaneous injection.

The present invention is found through experiments that guaiol can modify M2 macrophage phenotype, promote M2 macrophage to Macrophages turn without induced activation, to the cell of the expression of the property of Macrophage Surface marker, macrophages secrete because Expression, expression, the expression of M2 macrophage protein of M2 macrophage mRNA etc. of son significantly inhibit, by right The inhibition of M2 macrophage achievees the purpose that inhibit tumour growth, invasion and transfer, to realize the treatment to tumour.More it creates Alcohol provides new thinking as a kind of efficient antitumorigenic substance of low toxicity, for treatment tumour, has very big prospect in medicine.

Detailed description of the invention

Fig. 1 is various concentration guaiol on the active influence of M2 macrophage proliferation.Wherein, A is that CCK-8 detects cell life Deposit rate；B is cells survival rate and the IC50 value of guaiol effect on 24 hours nodes.

Fig. 2 is in vitro study of the guaiol to M2 macrophage phenotype inhibiting effect.Wherein, A is morphological change；B is Flow Cytometry detects M2 surface antigen CD206 expression；C is statistical result.

Fig. 3 is that macrophage removes model flow figure.

Fig. 4 is In vivo study of the guaiol to M2 macrophage inhibiting effect.Wherein, A is mouse weight variation；B is small Mouse peripheral blood IL-10 expression；C is the expression of mouse subcutaneous transplanting tumor macrophage surface antigen；D is that mouse spleen macrophage is thin Cellular surface antigen presentation；E is the expression of mouse subcutaneous transplanting tumor M2 macrophage mRNA；F is mouse subcutaneous transplanting tumor M2 macrophage The expression of cell protein.

Specific embodiment

The invention will be further elucidated with reference to specific embodiments.It should be understood that these embodiments are merely to illustrate this hair It is bright rather than limit the scope of the invention；In addition, it should also be understood that, after having read the content of the invention recorded, art technology Personnel can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited Fixed range.Ability is pressed in the unspecified commercially available acquisition of reagent instrument of the present invention, unspecified method operation Domain routine operation or manufacturers instruction carry out.

Experimental material

1.1 drug

Guaiol (-)-Guaiol: chemical name: (3R, 6S, 10S) -6,10, α, α-tetramethyl two ring [5.3.0] decyl- 1 (7)-alkene -3- methanol, chemical formula: C15H26O, molecular weight: 222.37.Sigma Co., USA, article No.: 29242-250MG.It adopts 4 DEG C of 20 μM of mother liquors are configured to methanol to store for future use.

1.2 zoopery

Healthy male C57BL/6 mouse, cleaning grade, weight 18-22g, 4-6 week old, Shanghai Si Laike experimental animal are limited Company；Liposome Clodronate/Liposome PBS: Amsterdam, the Netherlands Vrije University (https: // Clodronateliposomes.com, the Netherlands), article No.: 40337ES05/10,40338ES05/10.

1.3 cell culture

Lewis lung cancer cell line (Lewis lung cancer cell, abbreviation LLC) and RAW264.7 (mouse leukemia Mononuclear macrophage strain): Shanghai life science institute, Chinese Academy of Sciences cell bank；DMEM culture solution (contains 1% blueness/streptomysin): beauty HyClone company, state；Fetal calf serum (FBS): Gibco company, the U.S. is made into the complete medium containing 10%FBS before use, and 4 DEG C Refrigerator saves backup；M-CSF: Peprotech company, the U.S., article No.: 315-02-50；IL-4: R&D company, the U.S., article No.: BC1817031。

1.4 Flow Cytometries (FACS)

FITC-F4/80, PE-CD206 antibody: Peprotech company, the U.S.；Tumor tissues dissociate kit: Germany Miltenyi company, article No.: 130-096-730；Spleen dissociates kit: German Miltenyi company, article No.: 130-095- 926；GentleMACS 25C Tubes: German Miltenyi company, article No.: 130-093-237；Gentle MACS organizes place Manage device: German Miltenyi company；100um strainer: Corning company, the U.S..

1.5 real-time fluorescence quantitative PCRs (RT-PCR)

PrimeScriptTM RT Master Mix (Perfect Real Time): Japanese TaKaRa company, article No. RR036A；SYBRPrime Ex TaqTM: Japanese TaKaRa company, article No. RR420A.

1.6 detected by Western blot (Western Blot)

GAPDH primary antibody: CST company, the U.S., article No.: 2118S；CD206 primary antibody: Immunoway company, article No.: YT0739； IL-10 primary antibody: abcam company, the U.S., article No.: ab189393；Anti- rat IgG secondary antibody: CST company, the U.S., article No.: #7077；It is anti- Rabbit igg secondary antibody: CST company, the U.S., article No.: #7074.

In vitro study of 1 guaiol of embodiment to M2 macrophage phenotype inhibiting effect

The foundation of 1 external M2 Macrophage Model

It is carried out using mouse bone marrow cells source property macrophage (Bone marrow-derived macrophage, BMDM).It takes Healthy C57BL/6 male mice, 6~8 week old, 18~22g of weight put to death mouse cervical vertebra, with 75% alcohol disinfecting mouse Skin of abdomen, then makes it in dorsal position, and four limbs expansion is fixed in dissection plate.Mouse peritoneal is opened under aseptic condition, takes stock Bone removes muscle, and eye scissors cut off both ends, draws the DMEM culture solution containing 10%FBS with syringe, blows and beats out bone marrow cell, It is blown and beaten repeatedly with liquid-transfering gun, the use of aperture is 100um strainer filtering, weed out impurity, 300g is centrifuged 10min, and gained precipitating is The mouse bone marrow cells monocyte of collection is inoculated in 6cm culture dish by mouse bone marrow cells monocyte, and M-CSF, which is added, keeps it dense eventually Degree is 10ng/ml, is placed in 5%CO2, cultivates in 37 DEG C of cell incubators.It is cleaned per daily PBS, discards non-attached cell, replaced Culture solution, continuous culture 7 days, obtains BMDM primary cell.

The good BMDM primary cell of upgrowth situation is taken, cell concentration 1 × 10 is made⁶A/mL, addition concentration are 20ng/ The IL-4 induction of ml for 24 hours, establishes the M2 type macrophage of induced activation.

2 experimental results

2.1 guaiols act on the effective concentration screening of macrophage

The external guaiol that carries out determines reasonable activity and time, selects to macrophage useful effect concentration screening The concentration and time range taken should be adjustable macrophage phenotype while the lethal effect for not causing macrophage.

The inhibition that we use CCK-8 Germicidal efficacy various concentration guaiol to be proliferated mononuclear macrophage strain RAW264.7 Effect, to determine reasonable function concentration and the time of further experiment guaiol.The results show that with the raising pair of guaiol concentration RAW264.7 cell Proliferation generates inhibiting effect, and CCK-8 experimental result is Figure 1A, and acting on 24 hours IC50 values is 232.1 μM, 95%CI (160.8,396.2), Figure 1B.20 μM to 80 μM ranges of guaiol concentration range that we select, action time 24 Hour, as next step experimental study concentration range.

In vitro study of 2.2 guaiols to M2 macrophage phenotype inhibiting effect

First using the M2 Macrophage Model of IL-4 induced activation in vitro, for 24 hours after, give 0 μM, 20 μM, 40 μ respectively M, the guaiol of 60 μM, 80 μM concentration.We are before and after ultramicroscopic observation induction and guaiol treated macrophage Metamorphosis.The variation of macrophage morphology is taken pictures, sees Fig. 2A.Macrophage without IL-4 induced activation is rounded, few Amount is in polygonal, and the macrophage differentiation after IL-4 induced activation is M2 type, and cell is in shuttle shape, and stretches out a large amount of pseudopodium, more M2 macrophage morphology is similar to the macrophage morphology without induced activation after creating alcohol processing.Illustrate that guaiol is thin to M2 macrophage Born of the same parents' phenotype has adjustment effect.

Membrane antigen CD206⁺Expression variation be the main marker of M2 macrophage, therefore we using streaming it is thin Double positive expressions of the detection of born of the same parents' technology M2 type Macrophage Surface marker F4/80, CD206.FCM analysis the results show that Compared with 0 μM of concentration group, the guaiol of 40 μM, 60 μM concentration groups is most significant to the inhibiting effect of M2 macrophage, flow cytometer detection Result figure 2B, respectively 64.6 ± 2.5%, 42.3 ± 2.8%, difference is statistically significant (P < 0.001), Fig. 2 C.Explanation is cured It is inhibited to M2 macrophage phenotype to create alcohol.

Inhibiting effect of 2 guaiol of embodiment to Lewis lung cancer in mice subcutaneous transplantation tumor and spleen M2 macrophage

1 experimentation

1.1 macrophages remove the foundation and grouping administration of mouse model

The healthy male C57BL/6 mouse of cleaning grade is taken, 4 groups is randomly divided into, is respectively as follows: Liposome PBS- physiological saline Group (M+/Control), Liposome PBS- guaiol group (M+/Guaiol), Liposome Clodronate- physiological saline Group (M-/Control), Liposome Clodronate- guaiol group (M-/Guaiol), using LLC cell inoculation in The right omoplate position of C57BL/6 mouse is subcutaneous, and the cell density of inoculation is 1 × 10⁶A/0.2mL/ only, establishes subcutaneous transplantation tumor mould Type.Macrophage scavenger (Liposome Clodronate/ was accordingly injected to 4 groups of mouse peritoneals in 2 days before being inoculated with LLC cell Liposome PBS), only, the 0th day starts every 4 days intraperitoneal injection Liposome Clodronate/Liposome 0.2ml/ Only, the subcutaneous visible 3-5mm size tumor mass of omoplate, starts accordingly to inject 4 groups of mouse peritoneals on the right side of about 1 week by PBS 0.1ml/ Guaiol (8mg/kg/2 days)/physiological saline 0.2ml.It is as shown in Figure 3 that macrophage removes model flow.

1.2 sample reception

28th day arrival experimental endpoints, weigh each group mouse weight, take mouse peripheric venous blood using eyeball blood taking method, and 4 3000rpm after DEG C static 2h is centrifuged 30min, takes supernatant, and -80 DEG C of refrigerators save.Implement de- neck to put to death, removes fresh spleen And tumor tissues, a part carry out single cell suspension preparation, and -80 DEG C of refrigerators of a part, which save, carries out RNA and protein extraction, and one 4% paraformaldehyde is divided to fix.

1.3 Flow Cytometries (FACS)

Cell is collected, cell quantity about 1 × 10 is adjusted⁶It is a.Tumor tissues and spleen are dissociated, single cell suspension is prepared, according to Book carries out as directed, and mixing enzyme solutions are successively added into gentle MACS C pipe；By fresh mouse tumor tissue/spleen group It knits and is cut into 2-4mm size addition C pipe；C pipe is installed in the casing of gentle MACS tissue processor, runs gentle MACS program；After EP (end of program), cell suspension is transferred to 15ml centrifuge tube from C pipe, is centrifuged 300g, 5min；100um strainer mistake Single cell suspension is collected in filter；Adjust cell quantity about 1 × 10⁶It is a.Each group sequentially adds fluorescence antibody, and 4 DEG C are protected from light incubation 30min；PBS washs antibody, and streaming instrument carries out machine testing；As a result it is analyzed using Flowjo software.

1.4 real-time fluorescence quantitative PCRs (RT-PCR)

Cell collects/subcutaneously tumor tissue homogenate.TRIZON carries out total serum IgE extraction；CDNA synthesis according to kit illustrate into Row sets reaction condition: 37 DEG C of 15min, 87 DEG C of 5s, 4 DEG C of ∞；Real-Time PCR illustrates to carry out according to kit, purpose base Because of primer sequence: Arg-1:F (5 ' -3 ')-GGTTCTGGGAGGCCTATCTT, R (5 ' -3 ')-CACCTCCTCTGCTGTCTTCC； IL-10:F (5 ' -3 ')-CTGCTATGCTGCCTGCTCTTACTG, R (5 ' -3 ')-ATGTGGCTCTGGCCGACTGG, setting are expanded Increase program: 95 DEG C of 30s, 95 DEG C of 5s, 60 DEG C of 30s, 95 DEG C of 30s, 37 circulations, 72 DEG C of detection signals.Data processing uses 2^-ΔΔCt Calculate the relative expression quantity of gene.

1.5 protein immunoblots (Western Blot)

Cell collects/subcutaneously tumor tissue homogenate.RIPA (containing 1%PMSF) is cracked, and BCA albuminimetry measures albumen Concentration；Equal protein (50 μ g/ swimming lane) loading；Using 10%SDS-PAGE electrophoresis: upper layer glue 80V, lower layer glue 120V；It is permanent on ice Press 100V transferring film；Primary antibody is incubated for 4 DEG C overnight, and secondary antibody is incubated for room temperature 1 hour；The exposure of ECL chemoluminescence method.

1.6 data statistics

It is carried out using SPSS 20.0.

2 experimental results

The influence of 2.1 pairs of mouse weights

Experimental endpoints, the average weight of each group mouse be respectively as follows: 23.3 ± 0.27g, 23 ± 0.78g, 23.27 ± 0.47g, 22.9 ± 0.55g.The results show that mouse weight no significant difference (P > 0.05) between each group, Fig. 4 A.Illustrate guaiol pair Experiment mice is without apparent toxic side effect.

The influence of the relevant expression of 2.2 pairs of M2 type macrophages

IL-10 is the cell factor of M2 macrophages secrete, closely related with M2 macrophage.Therefore ELISA skill is used Art detect mouse peripheral blood IL-10 expression, the results show that guaiol have to Lewis lung cancer in mice peripheral blood IL-10 it is aobvious The inhibiting effect of work, compared with the control group, difference are statistically significant (P < 0.001), Fig. 4 B.Illustrate that guaiol has IL-10 Apparent inhibiting effect.

The expression quantity of the M2 type macrophage of mouse knurl and spleen is detected using Flow Cytometry, the results show that more Wound alcohol has significant inhibiting effect, each group knurl M2 type macrophage to the M2 type macrophage of Lewis lung cancer in mice knurl and spleen The expression quantity of cell surface antigen CD206 is respectively as follows: 23.78 ± 5.78%, 14.9 ± 3.91%, 12.31 ± 3.34%, 12.875 ± 4.97%.The expression quantity of spleen M2 type macrophage surface antigen CD206 is respectively as follows: 23.09 ± 1.05%, 5.43 ± 2.34%, 5.26 ± 1.09%, 2.34 ± 0.93%.Compared with Liposome PBS- physiological saline group, each group is tested The expression quantity of CD206 is remarkably decreased, and (P < 0.001), difference is statistically significant, Fig. 4 C-D.Illustrate guaiol to M2 macrophage Cell has apparent inhibiting effect.

The expression that mRNA and albumen are detected using RT-PCR and Western Blot technology, the results show that guaiol pair The M2 type macrophage and relevant cell factor IL-10mRNA and protein expression of Lewis lung cancer in mice knurl and spleen have aobvious The inhibiting effect of work, Fig. 4 E-F.Illustrate that guaiol has apparent inhibiting effect to M2 macrophage.

The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art Member, under the premise of not departing from the method for the present invention, can also make several improvement and supplement, these are improved and supplement also should be regarded as Protection scope of the present invention.

Claims (9)

1. application of the guaiol in the drug that preparation inhibits tumour correlation M2 type macrophage.

2. application according to claim 1, which is characterized in that the guaiol is thin as inhibition tumour correlation M2 type macrophage The drug of the sole active agent of the drug of born of the same parents or M2 type macrophage related to other inhibition tumours is collectively as active constituent.

3. according to claim 1 or 2 any applications, which is characterized in that the guaiol inhibits M2 type macrophage in preparation Application in the drug of cell-proliferation activity.

4. according to claim 1 or 2 any applications, which is characterized in that the guaiol promotes M2 type macrophage in preparation Application of the cell into the drug of the conversion of the macrophage without induced activation.

5. according to claim 1 or 2 any applications, which is characterized in that the guaiol inhibits M2 type macrophage in preparation Application in the drug of expression.

6. a kind of drug for inhibiting tumour correlation M2 type macrophage, which is characterized in that the active constituent of the drug is more to create Alcohol.

7. drug according to claim 6, which is characterized in that the drug for inhibiting tumour correlation M2 type macrophage is also Including pharmaceutically acceptable carrier.

8. drug according to claim 7, which is characterized in that the pharmaceutically acceptable carrier include emulsifier, Excipient, filler, adhesive, wetting agent, disintegrating agent, sorbefacient, flavoring agent, colorant or cosolvent.

9. drug according to claim 6, which is characterized in that the dosage form of the drug be pulvis, granule, tablet, Capsule, pill, solution, suspension or injection.