CN108329381A - A kind of ten hexapeptides from Eucheuma and its application in preparing prevention Malignant tumor of bonal metastasis drug - Google Patents
A kind of ten hexapeptides from Eucheuma and its application in preparing prevention Malignant tumor of bonal metastasis drug Download PDFInfo
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- A61K38/00—Medicinal preparations containing peptides
Abstract
The invention discloses a kind of ten hexapeptides from Eucheuma and its preparing the application in preventing Malignant tumor of bonal metastasis drug.The amino acid sequence of ten hexapeptide is：Xaa（1）‑Xaa（2）‑Gly‑Ala‑Cys‑Phe‑Cys‑Xaa（8）‑Xaa（9）‑Tyr‑Xaa（11）‑Gly‑Xaa（13）‑Xaa（14）‑Tyr‑Pro（SEQ ID No.2）；Wherein, Xaa（1）=Arg or Lys, Xaa（2）=Thr or Ser, Xaa（8）=Val or Ile or Leu, Xaa（9）=Ile or Val or Leu, Xaa（11）=Asn or Gln, Xaa（13）=Ile or Val or Leu, Xaa（14）=Leu or Ile or Val.By internal and external test prove the polypeptide its shift with good inhibition malignant cell, diffusion, especially inhibit the Malignant tumor of bonal metastasis such as liver cancer, lung cancer and breast cancer, it can prepare as antitumor drug, a kind of new effective selection is provided for antitumor field.
Description
Technical field
The invention belongs to biomedicine technical fields.More particularly, to a kind of ten hexapeptides from Eucheuma and its
Preparing the application in preventing Malignant tumor of bonal metastasis drug.
Background technology
Metastases refer to malignant cell from original site, and through lymphatic channel, the approach such as blood vessel or body cavity reach other
This process of position continued growth.This characteristic of malignant tumour, it should referred to as spread.The transfer of malignant tumour is often swollen
The main reason for tumor treatment failure.Common metastases position is lung, liver, bone, brain etc..Metastatic carcinoma not necessarily cancer
The early stage in late period, certain cancers can also shift.Why metastatic carcinoma is different from primary carcinoma, is because its formation is one
Multifactor, too many levels continuous dynamic process.Metastasis cancer cell has more active motility and more powerful drug resistance, especially
It is to have abundant new vessels and growth rate is greatly accelerated, and have the fastness of bigger to place side's immune function.Treatment
Metastatic carcinoma, it should be multiple target point, the composite construction drug more being oriented to.Tumour is the Health Killer of 21 century, incidence and dead
It dies rate still riseing, but still lacks effectively preventing tumor metastasis medicine at present.
It is mainly at present chemotherapy and radiation means to the therapy of tumor patient, human body is caused greatly to damage, tumour
Which kind of occur after pernicious transfer no matter mode to be all difficult thoroughly to cure with.So a kind of cancer cell that can thoroughly remove of searching is without damaging
The therapy of evil to other cells becomes the research hotspot of global medical oncology field.
Several Active Peptides are found to have antitumor activity one by one, this becomes antitumor drug research and development
New direction.Eucheuma（Eucheuma）, be also acanthopeltis japonica Okamura, chicken glue dish, belong to the frond plumpness fleshiness of algae, it is cylindric, it is flat pressure or
Flat, radiation or two lateral branchings, there are about 20 kinds, China is tropical seaweed, has very high medical value the category there are about 5 kinds.
It is found through retrieval, at present there is no the functions that document report Eucheuma borne peptides inhibit Malignant tumor of bonal metastasis, at home and abroad not
It was found that the report used with the drug of Eucheuma borne peptides work prevention Malignant tumor of bonal metastasis or health products.
Invention content
The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art, provide a kind of from the 16 of Eucheuma
Peptide.Ten hexapeptide compounds can significantly inhibit transfer and the invasion activity of malignant cell, and there is significant prevention to dislike
Property metastases function, can be applied to field of biological pharmacy.
The object of the present invention is to provide a kind of functional polypeptides from Eucheuma.
Another object of the present invention is to provide to be prepared prevention or is being inhibited pernicious by above-mentioned functional polypeptide or its simulating peptide
Metastases, the drug of diffusion or the application in health products.
The purpose of the present invention is realized by following technical proposals：
The present invention relates to a kind of functional polypeptide, which is ten hexapeptides, and amino acid sequence is：
Xaa（1）-Xaa（2）-Gly-Ala-Cys-Phe-Cys-Xaa（8）-Xaa（9）-Tyr-Xaa（11）-Gly-Xaa（13）-
Xaa（14）-Tyr-Pro（SEQ ID No.1）；
Wherein, Xaa（1）=Arg or Lys（Arg, Lys are all basic amino acid）, Xaa（2）=Thr or Ser（Thr, Ser are all to contain
Hydroxy-amino-acid）, Xaa（8）=Val or Ile or Leu（Val, Ile, Leu are all branched-chain amino acid）, Xaa（9）=Ile or Val or
Leu（Val, Ile, Leu are all branched-chain amino acid）, Xaa（11）=Asn or Gln（Asn, Gln are all the amino of amine groups containing aminoacyl
Acid）, Xaa（13）=Ile or Val or Leu（Val, Ile, Leu are all branched-chain amino acid）, Xaa（14）=Leu or Ile or Val
（Val, Ile, Leu are all branched-chain amino acid）；Wherein,
Arg indicates that English name is Arginine, and Chinese is the corresponding residue of arginic amino acid；
Lys indicates that English name is lysine, and Chinese is the corresponding residue of the amino acid of lysine；
Thr indicates that English name is Threonine, and Chinese is the corresponding residue of the amino acid of threonine；
Ser indicates that English name is Serine, and Chinese is the corresponding residue of the amino acid of serine；
Gly indicates that English name is Glycine, and Chinese is the corresponding residue of the amino acid of glycine；
Ala indicates that English name is Alanine, and Chinese is the corresponding residue of the amino acid of alanine；
Cys indicates that English name is Cysteine, and Chinese is the corresponding residue of the amino acid of cysteine；
Phe indicates that English name is phenylalanine, and Chinese is the corresponding residue of the amino acid of phenylalanine；
Val indicates that English name is Valine, and Chinese is the corresponding residue of the amino acid of valine；
Ile indicates that English name is IsoLeucine, and Chinese is the corresponding residue of the amino acid of isoleucine；
Leu indicates that English name is Leucine, and Chinese is the corresponding residue of the amino acid of leucine；
Tyr indicates that English name is Tyrosine, and Chinese is the corresponding residue of the amino acid of tyrosine；
Asn indicates that English name is Asparagine, and Chinese is the corresponding residue of asparagine；
Gln indicates that English name is Glutamine, and Chinese is the corresponding residue of the amino acid of glutamine；
Pro indicates that English name is proline, and Chinese is the corresponding residue of the amino acid of proline.
Preferably, the functional polypeptide is abbreviated as RTGACFCVIYNGILYP, and amino acid sequence is：Arg-Thr-Gly-
Ala-Cys-Phe-Cys-Val-Ile-Tyr-Asn-Gly-Ile-Leu-Tyr-Pro（SEQ ID No.2）.
Further, have and pass through on the basis of amino acid sequence shown in the SEQ ID No.1 or SEQ ID No.2
Replace after one or several amino acid and the polypeptide with same or similar function, also within protection scope of the present invention.
The invention further relates to the functional polypeptides or its pharmaceutically acceptable salt to prepare prevention or treat pernicious swollen
The drug of tumor or the application in health products.
The invention further relates to the functional polypeptides or its pharmaceutically acceptable salt to prepare prevention or inhibit pernicious swollen
The drug or health products of tumor metastasis, diffusion, or prepare prevent or inhibit Malignant tumor of bonal metastasis, diffused drugs it is effective at
Point, or preparing the new application in preventing or inhibit the prodrug of Malignant tumor of bonal metastasis, diffusion to be transformed.
Malignant tumor of bonal metastasis of the present invention includes transfer in vivo or external transfer.
Further, the malignant tumour includes liver cancer, lung cancer or breast cancer.
Further, the liver cancer is HepG2 cells, and lung cancer is A549 cells, and breast cancer is MCF-7 cells.
Functional polypeptide of the present invention can be used alone, and can also be used in combination with other drugs.
The invention further relates to the drug of a kind of mitigation or inhibition Malignant tumor of bonal metastasis diffusion, including the functional polypeptide or
The prodrug of its pharmaceutically acceptable salt or the functional polypeptide.
The pharmaceutically acceptable salt of functional polypeptide of the present invention, the preferably functional polypeptide are formed medically with acid
Acceptable salt.
The acid includes organic acid and inorganic acid.
Preferably, the inorganic acid is hydrochloric acid, sulfuric acid or phosphoric acid, and the organic acid is acetic acid, oxalic acid, citric acid, rich horse
Acid, malic acid or lactic acid.
The prodrug or prodrug of the functional polypeptide are often referred to a kind of substance, can be after being applied with method appropriate
It is metabolized in subject's body or chemically reacts and be transformed into the functional polypeptide or its salt.
Preferably, the drug also includes pharmaceutically acceptable auxiliary material or carrier.
Wherein, the pharmaceutically acceptable carrier will not destroy the pharmaceutical active of functional polypeptide of the present invention, lead to
Often approved for this purpose and as the non-active ingredient of medicament by sanitarian.Remittance in relation to pharmaceutically acceptable carrier
Compiling can be《Handbook of pharmaceutical excipients》（Handbookof Pharmaceutical excipients, second edition, by A.Wade
It is edited with P.J.Weller；AmericanPharmaceutical Association are published, Washington and The
Pharmaceutical Press, London, 1994）It is found in equal reference books.
It is of the present invention mitigation or inhibition metastases diffusion drug, can make according to actual needs piece agent,
Capsule, pill, powder, granule, syrup, solution, injection, spray, aerosol or patch.
The drug of mitigation or inhibition metastases diffusion of the present invention, can be prepared, and can by this field conventional method
With by through gastrointestinal administration or it is non-through gastrointestinal administration approach be administered.
Preferably, described non-through gastrointestinal administration strategy and suggestion drug administration by injection, respiratory tract administration, percutaneous drug delivery, mucous membrane
Administration or cavity/canal drug administration.
Wherein, non-to select injection, spray, aerosol, patch etc. through gastrointestinal administration medicament；It is given through gastrointestinal tract
Medicine preparation can select tablet, capsule, powder, granule, pill, solution or syrup etc..
The administration route of the drug of mitigation or inhibition metastases diffusion of the present invention can be oral, sublingual, warp
Muscle or subcutaneous, vein, urethra, vagina etc..
Functional polypeptide of the present invention can have following a variety of methods in the application of prevention Malignant tumor of bonal metastasis：
Such as：10~50 mg/kg of functional polypeptide compound of the present invention is taken orally, once a day, continuous medication at least 35 days；Note
0.1~1 mg/kg of function Eucheuma polypeptide compound of the present invention is penetrated, every 3 days primary, continuous medication at least 35 days；With it is current
The treatment malignant tumor medicine use in conjunction used takes orally 10~50 mg/kg of Eucheuma polypeptide compound, once a day.
Functional polypeptide of the present invention can isolate and purify to obtain from Eucheuma, can also using amino acid as raw material,
It is artificial synthesized according to the amino acid sequence described in SEQ ID No.1 with Peptide systhesis instrument, then use high-efficient liquid phase chromatogram purification.
The present invention also provides a kind of separation, purifying and the identification method of ten hexapeptides from Eucheuma, including it is following
Step：
（1）Eucheuma is acquired, is cleaned with tap water 2~3 times, then rinsed repeatedly with distilled water 1~2 time, is weighed after drying repeatedly；
（2）The Eucheuma dried is placed in the solution of pH=3~5 and is impregnated, homogenate is smashed, after 8000 r/min centrifuge 30 min
Collect supernatant；
（3）It is centrifuged again after 1%~2% KCl is added into supernatant, it is spare to collect supernatant；
（4）Supernatant Sephadex G-50 are detached, 15~25 mmol/L hydrochloric acid elution, 1.0 mL/min of flow velocity is collected
280 nm have optical absorption peak substance, collect eluting peak altogether, obtain polypeptide solution；
（5）Further distinguish purification step with high performance liquid chromatography（4）Obtained polypeptide solution, and identified activity；It will be active
Polypeptide LC-MS/MS Instrumental Analysis polypeptide sequences.
Compared with prior art, the invention has the advantages that：
（1）The present invention has synthesized the functional polypeptide for the first time, which has prevention Malignant tumor of bonal metastasis diffusion well
Effect has good application prospect in biomedicine field.
（2）The functional polypeptide of the present invention can prepare the drug of prevention Malignant tumor of bonal metastasis or the active ingredient or medicine of drug
Object precursor or health products.
（3）The present invention contains the drug or health products of functional polypeptide, and it is more that pulvis or injection or product etc. can be made
Kind form, can use separately as finished product, can also be used as the adjuvants combo such as active ingredient and physiological saline, glucose solution
At composition, or can also be with treatment Malignant tumor of bonal metastasis Drug combination used at present.
Description of the drawings
Fig. 1 is that the functional polypeptide inhibits cancer metastasis in vitro.
Fig. 2 is that the functional polypeptide inhibits cancer cell invasion in vitro.
Fig. 3 is to inhibit the transfer of cancer cell lung in the functional polypeptide body.
Fig. 4 is to inhibit cancer cell hepatic metastasis in the functional polypeptide body.
Specific implementation mode
It is further illustrated the present invention below in conjunction with specific embodiment.Following embodiment is the preferable embodiment party of the present invention
Formula, but protection scope of the present invention is not limited in any form.Unless stated otherwise, the present invention uses reagent, side
Method and equipment are the art conventional reagent, method and apparatus.
Unless stated otherwise, following embodiment agents useful for same and material are purchased in market.
1 functional polypeptide of embodiment（Ten hexapeptides）It prepares
1, separation, purifying and the identification method of a kind of ten hexapeptides from Eucheuma, includes the following steps：
（1）Eucheuma is acquired from Qionghai, cleans 2~3 silt sundries for removing Eucheuma surface repeatedly with tap water, then
It is rinsed 1~2 time, is dried spare after weighing repeatedly with distilled water；
（2）The Eucheuma dried is placed in the solution of pH=3 and is impregnated, homogenate is smashed, and homogenate is obtained, with 8000 r/ of centrifuge
Min collects supernatant after centrifuging 30 min homogenates；
（3）It is centrifuged again after 1.5% KCl is added into supernatant, it is spare to collect supernatant；
（4）Supernatant Sephadex G-50 are detached, 20 mmol/L hydrochloric acid elution, 1.0 mL/min of flow velocity collects 280
Nm has optical absorption peak substance, collects eluting peak altogether, obtains polypeptide solution；
（5）Further distinguish purification step with high performance liquid chromatography（4）Obtained polypeptide solution, and identified activity；It will be active
Polypeptide LC-MS/MS Instrumental Analysis polypeptide sequences.
2, result：The product of 95% or more purity is obtained, and is identified through LC-MS/MS, final analysis determination is obtained more
Peptide is ten hexapeptides, is abbreviated as RTGACFCVIYNGILYP, amino acid sequence is：Arg-Thr-Gly-Ala-Cys-Phe-Cys-
Val-Ile-Tyr-Asn-Gly-Ile-Leu-Tyr-Pro。
Embodiment 2 prevents the experiment of metastases
1, the external inhibitory activity of polypeptide：The case where experiment detection cell migration of the cells Transwell and invasion
（1）Transwell Matrigels：
1）Matrigel is added, includes the following steps：
1. the Matrigel bought from Corning Costar companies to be dispensed into the EP pipes of 1.5 sterile mL, sealed with sealed membrane
It is placed on -20 DEG C of preservations well；The EP pipes containing Matrigel are taken out in first 24 hours of experiment, place on ice, are then put in 4 DEG C,
Keep its slow mechanism dissolved spare；
2. the Matrigel after thawing is placed on ice, Transwell plates and 24 orifice plates are put in -20 DEG C of pre- cold standbies, then from 4
It is 1 that DEG C refrigerator, which takes out the DMEM culture mediums of serum-free according to volume ratio,：3（Matrigel：Culture medium）Dilute Matrigel, mixing
It is placed on spare on ice；
3. taking out transwell plates and 24 orifice plates from -20 DEG C, the cells transwell are placed in 24 orifice bores with tweezers, so
The Matrigel after dilution is added in backward upper chamber, per 100 μ L of hole；
4. " 8 " word rocks 24 orifice plates, Matrigel is made to be evenly distributed in upper chamber, it is noted that avoiding generating gas when experimental implementation
Bubble, avoids poking microporous barrier, 24 orifice plates is then placed in 37 DEG C, contains 5% CO2Incubator in be incubated 30~50 min.
2）Cell culture
1. the tumour cell of logarithmic growth phase（Including human hepatoma HepG2 cell, typeⅡ pneumocyte and human breast carcinoma MCF-
7 cells）, cell count after digestion, it is 2.5 × 10 to prepare cell density with the DMEM culture mediums of serum-free5The cell suspension of/mL
It is spare；
2. taking out 24 orifice plates added with Matrigel from incubator, the culture medium in careful each upper chamber of reject is lifted with tweezers
Upper chamber is added 600 μ L in downward room and contains ten hexapeptide of 10% fetal calf serum and various concentration（RTGACFCVIYNGILYP）'s
Then upper chamber is gently put back to lower room by DMEM complete mediums, pay attention to avoiding generating bubble；Then 100 are added in each upper chamber
μ L cell suspensions, close the lid, rock mixing, are placed in 37 DEG C, contain 5%CO2Incubator in cultivate 24 h；
3. 24 orifice plates are taken out from incubator, the culture medium of upper chamber and lower room is removed with liquid-transfering gun, 600 μ are added in downward room
The PBS buffer solution of L gently rinses cell, and rinsing is three times；
4. with cotton swab by above upper chamber microporous barrier Matrigel and cell clean, then cell is placed in added with 600 μ L methanol
Lower room in it is fixed, be stored at room temperature 30 min, then cell be placed in the lower room added with the PBS buffer solution of 600 μ L and rinses three
It is secondary, 5 min every time；
5. after having rinsed, upper chamber being upside down in 24 orifice plates and is covered, makes the lower surface of upper chamber in ventilation natural air drying；
It is dyed 6. being placed in air-dried upper chamber in the lower room added with the lucky female Sa dye liquors of 600 μ L, is stored at room temperature 30 min；
It rinses, rinses three times, every time 5 min 7. upper chamber is put into PBS buffer solution after dyeing；
8. upper chamber is upside down on glass slide, is just setting microscopically observation and taking pictures；Randomly select 5 high power fields（×
100）Cell count is carried out, repeats experiment three times, and carry out statistical analysis.
（2）Transwell migration experiments：
It is not added with Matrigel, remaining experimental procedure is identical as above-mentioned Matrigel.
（3）Experimental result
Experimental result difference is as depicted in figs. 1 and 2.Transwell Matrigels are given the results show that compared with blank control group
Ten hexapeptides of medicine group 10 μ g/mL and 20 μ g/mL can significantly inhibit the invasive ability of liver cancer, lung cancer and breast cancer cell；Separately
Outside, Transwell migrates experimental result and shows, compared with blank control group, the 16 of administration group 10 μ g/mL and 20 μ g/mL
Peptide can significantly inhibit the transfer ability of liver cancer, lung cancer and breast cancer cell（*, compared with the control groupP<0.01）.Experimental result is said
Bright, ten hexapeptides of the invention are capable of the transfer and diffusion of notable malignant tumour.
2, in-vivo tumour shift experiment
（1）Experimental method：
1）Establish people's cancer Nude Mouse Model：Animal tumor model is established using culture cell allotransplantation method, first largely
Human hepatoma HepG2 cell, typeⅡ pneumocyte and MCF-7 Human Breast Cancer Cells are cultivated, then respectively carry out each group cell
Conventional digestion is simultaneously collected, and cell is gently blown and beaten with liquid-transfering gun makes it be uniformly dispersed, with Trypan Blue cell and living cell counting,
When viable count can be used for subsequent experimental more than 95%；
2）1000 r/min centrifuge 5 min, and remove complete medium, and the DMEM culture mediums without serum are then added and wash
Cell is primary, 1000 r/min, centrifuges 5 min, removes supernatant；
3）Suitable PBS is added or cell is resuspended without serum DMEM culture mediums, then carries out cell count, keeps cell suspension close
Degree is 5 × 107It is inoculated with as early as possible in/mL, 30 min, to prevent cellular activities from declining；
4）Selection nude mice tail vein is inoculation position；After partly sterilised, the cell that mixing is accurately drawn with 1 mL syringes is outstanding
Liquid, 0.2 mL cell suspensions of injection press lightly on the several seconds after inoculation to nude mice tail vein, are flowed out to prevent cell suspension；
Whole operation process strictly observes sterile working principle；
5）All nude mice normal diets, drinking-water after inoculating cell, and ten hexapeptides of feeding various concentration daily
（RTGACFCVIYNGILYP）.
6）Observe the daily living condition of mouse；The 6th week after intravenous injection cell, animal knot is put to death with cervical dislocation
Beam is tested, and nude mice is dissected, the various histoorgans such as liver, lung of nude mice are taken out；The tumour for finding transfer, compares three groups of nude mices
In the tissue the case where metastases.
7）After materials lung tissue fixes 24 h with 10% neutral formalin, it is conventional be dehydrated, paraffin embedding, for follow-up pathological section,
HE is dyed；Microscope photographing；Every nude mice lung tissue cuts 10 pathological sections.
（2）Experimental result
The experimental result of in-vivo tumour transfer is as shown in Figure 3 and Figure 4.By tail vein injection cancer metastasis experimental result it is found that
Ten hexapeptides from Eucheuma of the present invention significantly reduce hepatoma Hep G 2 cells, typeⅡ pneumocyte and people in vivo
The cancer stove quantity that the cancer cells such as MCF-7 Breast Cancer Cell are formed in lung and liver（*, compared with the control groupP<0.01）.Experiment
As a result illustrate, which has the function of inhibiting transfer in malignant tumour body.
The above embodiment is only the preferred embodiment of the present invention, and the scope of protection of the present invention is not limited thereto,
The variation and replacement for any unsubstantiality that those skilled in the art is done on the basis of the present invention belong to institute of the present invention
Claimed range.
Sequence table
<110>Guangdong medical university
<120>A kind of ten hexapeptides from Eucheuma and its application in preparing prevention Malignant tumor of bonal metastasis drug
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 16
<212> PRT
<213>Eucheuma (Eucheuma)
<400> 1
Xaa Xaa Gly Ala Cys Phe Cys Xaa Xaa Tyr Xaa Gly Xaa Xaa Tyr Pro
1 5 10 15
<210> 2
<211> 16
<212> PRT
<213>Eucheuma (Eucheuma)
<400> 2
Arg Thr Gly Ala Cys Phe Cys Val Ile Tyr Asn Gly Ile Leu Tyr Pro
1 5 10 15
Claims (10)
1. a kind of functional polypeptide, which is characterized in that the functional polypeptide is ten hexapeptides, and amino acid sequence is：
Xaa（1）-Xaa（2）-Gly-Ala-Cys-Phe-Cys-Xaa（8）-Xaa（9）-Tyr-Xaa（11）-Gly-Xaa（13）-
Xaa（14）-Tyr-Pro；Wherein, Xaa（1）=Arg or Lys, Xaa（2）=Thr or Ser, Xaa（8）=Val or Ile or Leu, Xaa
（9）=Ile or Val or Leu, Xaa（11）=Asn or Gln, Xaa（13）=Ile or Val or Leu, Xaa（14）=Leu or Ile or
Val。
2. functional polypeptide according to claim 1, which is characterized in that its amino acid sequence is Arg-Thr-Gly-Ala-
Cys-Phe-Cys-Val-Ile-Tyr-Asn-Gly-Ile-Leu-Tyr-Pro。
3. functional polypeptide described in claim 1 or its pharmaceutically acceptable salt are preparing the medicine for preventing or treating malignant tumour
Application in object or health products.
4. functional polypeptide described in claim 1 or its pharmaceutically acceptable salt are preparing prevention or malignant tumour are inhibited to turn
It moves, the application in the drug or health products of diffusion.
5. functional polypeptide described in claim 1 or its pharmaceutically acceptable salt are preparing prevention or malignant tumour are inhibited to turn
It moves, the application in the prodrug of diffusion.
6. according to claim 3~5 any one of them application, which is characterized in that the malignant tumour includes liver cancer, lung cancer
Or breast cancer.
7. according to claim 3~5 any one of them application, which is characterized in that the liver cancer is HepG2 cells, and lung cancer is
A549 cells, breast cancer are MCF-7 cells.
8. the drug of a kind of mitigation or inhibition Malignant tumor of bonal metastasis diffusion, which is characterized in that comprising as claimed in claim 1 or 2
The prodrug of functional polypeptide or its pharmaceutically acceptable salt or the functional polypeptide.
9. drug according to claim 8, which is characterized in that also include pharmaceutically acceptable auxiliary material or carrier.
10. drug according to claim 8, which is characterized in that the dosage form of the drug is tablet, capsule, pill, dissipates
Agent, granule, syrup, solution, injection, spray, aerosol or patch.
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| CN117511868A (en) * | 2023-12-06 | 2024-02-06 | 承德合润生物科技有限公司 | Method for realizing quick amplification of iNKT cells |
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| CN108329381B (en) | 2021-04-23 |
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