CN106943593A - Application of the anti-TSLP antibody in the chronic itch medicine of preventing and treating is prepared - Google Patents
Application of the anti-TSLP antibody in the chronic itch medicine of preventing and treating is prepared Download PDFInfo
- Publication number
- CN106943593A CN106943593A CN201710183139.8A CN201710183139A CN106943593A CN 106943593 A CN106943593 A CN 106943593A CN 201710183139 A CN201710183139 A CN 201710183139A CN 106943593 A CN106943593 A CN 106943593A
- Authority
- CN
- China
- Prior art keywords
- tslp antibody
- mouse
- chronic
- tslp
- antibody
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Abstract
The present invention relates to antipruritic field, and in particular to application of the anti-TSLP antibody in the chronic itch medicine of preventing and treating is prepared.It is verified by experiments, the chronic pruritis that anti-TSLP Antibody on Mouse allergic contact dermatitis of the present invention is induced improves significantly, and under dose therapeutically effective, the sports coordination ability of anti-TSLP Antibody on Mouse does not make significant difference.The anti-TSLP antibody of present invention display can be used as effective ingredient, it is further used for preparing antipruritic medicine, for the chronic pruritus of clinical treatment, the chronic itch especially caused by allergic contact dermatitis, and the antibody to sports coordination ability without notable side effect.
Description
Technical field
The present invention relates to treat chronic itch drug field, more particularly to anti-TSLP antibody in the chronic itch medicine of preparation preventing and treating
Application in thing.
Background technology
Itch is that one kind makes one have scratch desire and offending dermal sensation, is allergic contact dermatitis
(Allergic Contact Dermatitis, hereinafter referred to as ACD) common symptoms.ACD is very common in daily life
Disease of skin, while being also a kind of more dermatergosis of incidence rate.In terms of world wide, annual ACD morbidity
Rate up to 15-20%.ACD main clinic symptoms include red swelling of the skin, fash, decortication, blister and the itch that occurs together.Patient is in inflammation
Abnormal itch is often felt at disease position, triggers scratching repeatedly to disease sites, has a strong impact on patient's mood and the state of mind.Excessively
Scratch and often further induce scytitis, stimulate cutaneous nerve tip, further scratched so as to trigger, formed " itch-
Scratch " vicious circle.Even more serious person can also cause skin scabies secondary infection, it is necessary in time application part so that systemic antibiotics and
Hormone is treated.If therefore can effectively reduce itch, to improving patient's daily life quality dermatitis will be promoted to disappear and rehabilitation
It is significant.
The material that causes to itch, which can be itched by acting on periphery, feels the corresponding feel acceptor of itching of neuron expression, and excitement is itched feel neuron,
Initiation, which is itched, feels that signal (i.e. incoming action potential) is produced, and feel signal of itching further is transferred to brain metathalamus by tractus spinothalamicus
Trigger gargalesthesia in position.It is clinical at present to be treated for ACD patient's pruritis, it is the most frequently used with antihistamine.But numerous researchs are pointed out
Antihistamine treats the unsatisfactory curative effect of ACD pruritus, and can trigger the side effect such as dizzy, drowsiness, weak.Though histamine is body
It is interior it is classical cause material of itching, but many research in the recent period discloses histamine dependent/non-dependent feel path of itching and has also played weight in mediation itch process
Act on.Therefore, will be to treatment ACD if the feel path that can be itched using histamine dependent/non-dependent researches and develops corresponding antipruritic medicine as starting point
Caused chronic itch has significant application value and prospect.
Thymic stromal lymphopoietin (thymic stromal lymphopoietin, hereinafter referred to as TSLP) is one
Plant the cell factor of epithelial cell origin.TSLP can be by acting on by IL-7 receptor alpha chain (IL-7R α) and TSLP acceptors
(TSLPR) receptor complex constituted plays its biological activity.The factor pair activated dendritic cell and induction lymph are thin
The breaking up of born of the same parents and its subgroup, maturation has important regulating and controlling effect.There are some researches show TSLP is inducing and is promoting Th2 immune thin
Some allergic diseases of born of the same parents' mediation, including played important function during allergic asthma and allergic rhinitis etc..
Block TSLP signal paths or by that in anti-TSLP antibody and after TSLP, can substantially reduce and be mediated by TH2 immunocytes
Inflammatory reaction, respiratory inflammation and respiratory tract high response caused by Reduce allergy asthma, and mitigate anaphylaxis
Rhinitis Symptoms.
Although anti-TSLP antibody has certain therapeutic efficiency to above-mentioned disease, so far, there is not yet any relevant profit
Reported with the related application of the antibodies for treatment of chronic pruritus.
The content of the invention
It is an object of the invention to provide the new application of anti-TSLP antibody, and in particular to anti-TSLP antibody is chronic in preparation preventing and treating
Application in application in itch medicine, chronic itch disease drug caused by especially preparing preventing and treating ACD.
The purpose of the present invention is achieved through the following technical solutions：
1. anti-TSLP antibody is purchased from R＆D companies (Mouse TSLP antibody, article No.：MAB555)；
2. anti-TSLP antibody is used for the zoopery of chronic pruritus caused by treating ACD；
The mouse model of chronic pruritus caused by setting up ACD, after model is successfully established, chooses skin of neck 5 after mouse
Individual scattered different parts, the difference anti-TSLP antibody of subcutaneous injection, control group mice is carried out same then according to above-mentioned same procedure
Type control IgG is subcutaneously injected.After injection 30 minutes, Animal Behavior Science observes chronic itch caused by anti-TSLP Antibody on Mouse ACD
The influence of behavior.
As a result show：The chronic pruritis that anti-TSLP antibody is shown to ACD model mices, which has, significantly improves effect.
3. whether the anti-TSLP antibody of research produces the experiment of influence to the animal movement coordination ability：
In view of some antipruritic medicines (such as classical antihistamines) can cause it is drowsiness, dizzy and weak influence motion association
The side effect of tune ability, and these side effects often influence the Clinical practice of medicine.Therefore next, we further study
Whether anti-TSLP antibody produces influence to the sports coordination ability of mouse.
C57BL/6 male mices are selected in experiment, choose 5 scattered different parts of skin of neck after mouse, subcutaneous respectively
Anti- TSLP antibody is injected, control group mice then according to the method described above, carries out Isotype control IgG hypodermic injection.After injection is finished,
Accelerate roller method of testing using mouse, observe the influence of anti-TSLP Antibody on Mouse sports coordination.
As a result show：The dynamic coordination ability of anti-TSLP Antibody on Mouse is administered locally to have no significant effect.
The present invention has found chronic pruritus caused by administering locally to anti-TSLP Antibody on Mouse ACD models through animal experiment study
Shape has a significant inhibitory action, and administers locally to the dynamic coordination ability of anti-TSLP Antibody on Mouse and have no significant effect.This hair
This unique effect of bright found anti-TSLP antibody can further prepare the chronic itch for the treatment of as effective ingredient,
The medicine of chronic itch caused by especially ACD.
Brief description of the drawings
Fig. 1 (a) be in the chronic itch model of ACD induced mices after third time is smeared 0 hour of laccol (0.5%) model
The contrast statistical chart of group and control group, Fig. 1 (b) is to smear laccol in third time in the chronic itch model of ACD induced mices
(0.5%) the contrast statistical chart of model group and control group behind 4 hours, wherein, * p<0.05 and * * p<0.01；
After Fig. 2 is anti-TSLP antibody to smearing laccol (0.5%) 0 hour, the influence of the chronic itch behavior of ACD induced mices
* * p in comparison diagram, figure<0.01；
Fig. 3 is anti-TSLP antibody to smearing the influence of the chronic itch behavior of ACD induced mices after laccol (0.5%) 4 hour
* * p in comparison diagram, figure<0.01；
Fig. 4 is the influence comparison diagram of anti-TSLP Antibody on Mouse sports coordination, and NS is the significant difference of nothing statistically,
That is p>0.05.
Embodiment
The present invention is described further with reference to the accompanying drawings and examples.
Embodiment：
1. experimental animal：This experiment is from SPF grades of C57BL/6 male mices (being purchased from U.S. Jackson laboratories), 6-8
Week old, any to supply water and diet, 5 mouse/cages are raised, wherein solvent group 10, laccol group 10；Iso IgG groups 30,
TSLP neutralizing antibodies group 30.
2. experiment reagent is prepared：
1. sensibiligen is prepared：
2.0% laccol is prepared：Take the parts by weight of laccol 2 (Phytolab, article No.:81080, Vestenbergsgreuth, moral
State) volume ratio is dissolved in for 1：4 acetone and the parts by weight of mixed solvent 100 of olive oil, are mixed.
0.5% laccol is prepared：The parts by weight of laccol 0.5 are taken, the parts by weight of acetone 100 are dissolved in, mixed.
2. the preparation of anti-TSLP antibody and Isotype control IgG：By anti-TSLP antibody (R＆D companies, article No.：MAB555 it is) and same
Type control IgG (Sigma companies, article No.：I4131 500 μ g/ml solution) are configured to sterile phosphate buffer.
3. it is prepared by chronic itch model：
Experiment smears 50 μ l 2.0% from SPF grades of C57BL/6 male mices to mouse web portion (being handled in advance through shaving)
Laccol, and smear the laccols of 30 μ l 0.5% in neck (being handled in advance through shaving) after 5 days backward mouse.And control group mice is only applied
Smear coordinative solvent acetone.Method, every other day smears 0.5% laccol according to this, after being smeared through 3 times, can set up stable mouse
Chronic itch model caused by ACD.There is behavior of substantially scratching, and rear skin of neck compared with control group mice in model mice
There is substantially red and swollen, the sign such as decortication and scratch.
4. itch animal behavioral study：
Mouse is placed in the inspection box of lucite making 30 minutes first, environment pre-adaptation is carried out.Connect in rear neck
After being smeared by third time laccol (0.5%), mouse is placed in inspection box, using video camera from mouse surface to mouse behavior
Carry out behaviouristics record.Scratched with the one or many utilization rear solid ends of mouse to neck, and scratch finish after rear solid end is put into mouth
Or put back to ground and be defined as behavior of once scratching.The recording period of itch behaviouristics is after being smeared 0 and 4 hour through laccol, often
Secondary record 30 minutes.
5. anti-TSLP antibody administrations method：
Before third time smears laccol (0.5%) 30 minute, 5 scattered different parts of skin of neck after mouse are chosen,
Under Sevoflurane, anti-TSLP antibody, each μ l of injection location dosage 20,5 co-injections 100 of site one are subcutaneously injected respectively
μ l, the altogether anti-TSLP antibody of 50 μ g.Then with reference to the above method, with same dosage, Isotype control is subcutaneously injected in control group mice
IgG。
6. sports coordination is observed：
Continuous acclimatization training in 4 days is carried out using drum process is accelerated to mouse.Accelerate drum rotation speed be set as in 5 minutes from
5 revs/min are promoted to 40 revs/min.At the 5th day, 5 scattered different locis of neck after mouse were subcutaneously injected anti-
TSLP antibody, each μ l of injection location dosage 20,5 each sites have 100 μ l of injection altogether, altogether the anti-TSLP antibody of 50 μ g.Control group
Then with reference to the above method, with same dosage, Isotype control IgG is subcutaneously injected in mouse.And to mouse movement after injecting 30 minutes
Harmony is observed, and records the time-histories for starting from roller and falling up to it.Every mouse measures three times, every minor tick 5 minutes,
The average value of three time-histories measurements is taken as final result.
7. data analysis：
Experimental data represents with mean ± standard error (mean ± SE), using Origin8.0 software statistics and analyzes.Two groups
Between compare and examined using Student t, with p<0.05 thinks that difference has conspicuousness.
As a result show：
1) foundation of chronic itch model：
Found through Behavior test, after third time smears 0.5% laccol, ACD model mices show row of substantially scratching
For, and sustainable more than 4 hours of behavior of scratching (Fig. 1 (a) and (b) are shown), point out being successfully established for chronic itch model.
2) therapeutic action of the anti-TSLP antibody to chronic pruritus：
Before 30 minutes that third time smears 0.5% laccol, the anti-TSLP antibody of subcutaneous administration amounts to 50 μ g, and control group is given
Isodose Isotype control IgG.As a result show, give anti-TSLP antibody after 30 minutes, the itch behavior that mouse occurs is shown
Write alleviate (shown in Fig. 2), and anti-TSLP antibody antipruritic effect can continue until 4 hours after (shown in Fig. 3).
3) influence of anti-TSLP Antibody on Mouse sports coordination ability：
Anti- TSLP antibodyomes mouse, the anti-TSLP antibody of subcutaneous administration amounts to 50 μ g, and control group mice gives Isodose
Isotype control IgG.After administration 30 minutes, the sports coordination ability for accelerating drum process to examine mouse is utilized.As a result show, anti-TSLP
Antibodyome mouse points out anti-TSLP antibody having from accelerating fall time and Isotype control IgG groups on roller without marked difference
The mouse movement coordination ability is not made significant difference (shown in Fig. 4) under effect therapeutic dose.
The experimental result of the present invention confirms that the chronic of experimental animal performance can significantly be alleviated by administering locally to anti-TSLP antibody
Pruritis, and resist the effect of chronic itch lasting.This uniqueness for the anti-TSLP antibody that applicant is had found resists chronic scabies
The therapeutic action itched be different from it is previously reported in the therapeutical uses of this antibody that are previously mentioned.In addition, the present invention also has found first
Anti- TSLP antibody in use, has no effect on the sports coordination ability of experimental animal, and this feature is substantially better than tradition and controlled
Treat the antihistamine drug of pruritus.Therefore above-mentioned experimental evidence prompting, anti-TSLP antibody of the invention resists chronic itch to act on, can
As effective ingredient, further to prepare the medicine for resisting chronic pruritus.
Claims (3)
1. application of the anti-TSLP antibody in the chronic itch medicine of preventing and treating is prepared.
2. applied according to claim 1, it is characterised in that described chronic itch is caused by allergic contact dermatitis
Chronic itch.
3. applied according to claim 1, it is characterised in that described anti-TSLP antibody is Mouse TSLP
Antibody, article No. is MAB555.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710183139.8A CN106943593A (en) | 2017-03-24 | 2017-03-24 | Application of the anti-TSLP antibody in the chronic itch medicine of preventing and treating is prepared |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710183139.8A CN106943593A (en) | 2017-03-24 | 2017-03-24 | Application of the anti-TSLP antibody in the chronic itch medicine of preventing and treating is prepared |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106943593A true CN106943593A (en) | 2017-07-14 |
Family
ID=59472829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710183139.8A Pending CN106943593A (en) | 2017-03-24 | 2017-03-24 | Application of the anti-TSLP antibody in the chronic itch medicine of preventing and treating is prepared |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106943593A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113683694A (en) * | 2021-09-03 | 2021-11-23 | 江苏荃信生物医药有限公司 | Anti-human TSLP monoclonal antibody and application thereof |
| CN115400141A (en) * | 2022-09-20 | 2022-11-29 | 天津医科大学总医院 | Application of STING agonist in preparation of medicine for treating chronic pruritus |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101389657A (en) * | 2006-02-23 | 2009-03-18 | 诺瓦提斯公司 | Thymic stromal lymphopoietin (TSLP) antibodies and uses thereof |
| CN102257130A (en) * | 2008-10-22 | 2011-11-23 | 利发利希奥公司 | Compositions and methods for treating thymic stromal lymphopoietin (tslp)-mediated conditions |
| CN103845731A (en) * | 2012-12-05 | 2014-06-11 | 复旦大学 | Application of anti-ST2/IL-1R4 antibody in preparing medicament for preventing and treating pruritus |
| CN103933567A (en) * | 2007-10-25 | 2014-07-23 | 利发利希奥公司 | Compositions and methods for treating cystic fibrosis |
-
2017
- 2017-03-24 CN CN201710183139.8A patent/CN106943593A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101389657A (en) * | 2006-02-23 | 2009-03-18 | 诺瓦提斯公司 | Thymic stromal lymphopoietin (TSLP) antibodies and uses thereof |
| CN103933567A (en) * | 2007-10-25 | 2014-07-23 | 利发利希奥公司 | Compositions and methods for treating cystic fibrosis |
| CN102257130A (en) * | 2008-10-22 | 2011-11-23 | 利发利希奥公司 | Compositions and methods for treating thymic stromal lymphopoietin (tslp)-mediated conditions |
| CN103845731A (en) * | 2012-12-05 | 2014-06-11 | 复旦大学 | Application of anti-ST2/IL-1R4 antibody in preparing medicament for preventing and treating pruritus |
Non-Patent Citations (4)
| Title |
|---|
| KAPLAN DH等: ""Early immune events in the induction of allergic contact dermatitis"", 《NAT REV IMMUNOL》 * |
| KYUNGSOOK JUNG DVM等: ""Peroxisome proliferator-activated receptor γ-mediated suppression of dendritic cell function prevents the onset of atopic dermatitis in NC/Tnd mice"", 《J ALLERGY CLIN IMMUNOL》 * |
| STEFEN A等: ""A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation"", 《INT IMMUNOL》 * |
| 牟善初等: "《现代老年急症学》", 31 May 1997, 北京：人民军医出版社 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113683694A (en) * | 2021-09-03 | 2021-11-23 | 江苏荃信生物医药有限公司 | Anti-human TSLP monoclonal antibody and application thereof |
| CN115400141A (en) * | 2022-09-20 | 2022-11-29 | 天津医科大学总医院 | Application of STING agonist in preparation of medicine for treating chronic pruritus |
| CN115400141B (en) * | 2022-09-20 | 2023-08-11 | 天津医科大学总医院 | Application of STING agonist in preparation of medicine for treating chronic pruritus |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ullman | On the psyche and warts: I. Suggestion and warts: a review and comment | |
| Collombet et al. | Long-term effects of cytokine treatment on cognitive behavioral recovery and neuronal regeneration in soman-poisoned mice | |
| Prasad et al. | Efficacy of virtual reality in upper limb rehabilitation in patients with spinal cord injury: a pilot randomized controlled trial | |
| Huang et al. | The macroscopic and microscopic effect of low-frequency whole-body vibration after cerebral ischemia in rats | |
| US20030082212A1 (en) | Allergy treatment method using a rapid immunotherapy protocol | |
| CN102143687A (en) | Use of 4-aminopyridine to improve neuro-cognitive and/or neuro-psychiatric impairment in patients with demyelinating and other nervous system conditions | |
| Guo et al. | Enhancement of neural stem cell proliferation in rats with spinal cord injury by a combination of repetitive transcranial magnetic stimulation (rTMS) and human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) | |
| CN106943593A (en) | Application of the anti-TSLP antibody in the chronic itch medicine of preventing and treating is prepared | |
| JP2010531861A (en) | Parkinson's disease treatment | |
| JP2010531862A (en) | Parkinson's disease treatment | |
| Surman et al. | Hypnotic treatment of a child with warts | |
| Muñoz et al. | Influence of adrenergic blocking drugs upon the EEG analeptic effect of dl-amphetamine in conscious unrestrained rabbits | |
| Craske et al. | Qigong ameliorates symptoms of chronic fatigue: A pilot uncontrolled study | |
| CN103845731A (en) | Application of anti-ST2/IL-1R4 antibody in preparing medicament for preventing and treating pruritus | |
| RU2317805C2 (en) | Method for treating acute posttraumatic cephalgia cases | |
| CRISSEY et al. | A comparison of chloroquine and gold in the treatment of lupus erythematosus | |
| BURMAN | Clinical experiences with some curare preparations and curare substitutes | |
| CN107854620B (en) | Traditional Chinese medicine composition for improving cognitive dysfunction after brain injury and application thereof | |
| Song et al. | Clinical study on combined acupuncture and psychological desensitization therapy for anxiety due to heroin addiction | |
| Rubin | The psychopharmacology of lysergic acid diethylamide (LSD-25). | |
| US20220111229A1 (en) | Low-dose radiation therapy for traumatic brain injury and stroke | |
| Gresita et al. | Grafting of electrically stimulated subventricular neural stem cells embedded in a nutritional hydrogel into the stroke cavity improved cell survival and behavioural recovery in mice | |
| Wang et al. | Attenuation of kainic acid-induced epilepsy by butyrate is associated with inhibition of glial activation | |
| Tonetto et al. | Acupuncture in the treatment of burning mouth syndrome | |
| Yu et al. | Transdermal fentanyl for management of cancer pain in elderly patients in China |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170714 |