CN105664134B - It is a kind of for treating the pharmaceutical composition of osteocarcinoma - Google Patents

It is a kind of for treating the pharmaceutical composition of osteocarcinoma Download PDF

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Publication number
CN105664134B
CN105664134B CN201610143651.5A CN201610143651A CN105664134B CN 105664134 B CN105664134 B CN 105664134B CN 201610143651 A CN201610143651 A CN 201610143651A CN 105664134 B CN105664134 B CN 105664134B
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zlgat
polypeptide
osteocarcinoma
pharmaceutical composition
prt
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CN105664134A (en
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曹帅
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Zhejiang Pharmaceutical Garden Biotechnology Co., Ltd.
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Zhejiang Pharmaceutical Garden Biotechnology Co Ltd
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Priority to CN201910056802.7A priority Critical patent/CN109620949A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane

Abstract

The invention discloses application of the pharmaceutical composition in the drug of preparation treatment osteocarcinoma, described pharmaceutical composition contains ZLGAT polypeptide, can also be administered in combination with bortezomib.Its effective therapeutic dose is 0.1~20mg/Kg weight, can be oral administration, intravenous injection administration, subcutaneous administrations, administered intramuscular when administration.Experiments have shown that: polypeptide of the invention can inhibit growth of tumour cell, have good inhibiting effect to osteocarcinoma, tool has been widely used.

Description

It is a kind of for treating the pharmaceutical composition of osteocarcinoma
Technical field
The present invention relates to the drug of preparation treatment osteocarcinoma and its applications.
Background technique
Osteocarcinoma (Osteosarcoma) is a kind of malignant tumour grown by skeletal system, and is most normal in bone tumour The one kind seen can invade neighbouring tissue and organ, it is also possible to be transferred to other organs of distant place, be apt to occur in the age between ten With child and teenager between year to 20 years old, and male's occurrence probability is slightly above women.The pathogenesis of osteocarcinoma is so far It is unknown, by its original site and the age for mostly occurring in fast-growth, show that it increases and may have with the activity of osteoblast It closes, and inherent cause seems also to play a role in osteocarcinoma, further it is also possible to having with chronic inflammation, radiation or virus infection It closes.
For osteocarcinoma commonly-occurring disease in long bone end, there are about 50% to be located at nearly knee, can cause pain, swelling, even pathology Property fracture, and be likely to occur dyskinesia, part there is lump or other nonspecific symptoms such as weight loss, appetite not Vibration, feveret are had a pain in the back etc., and its death rate is very high, therefore osteocarcinoma is to make us the cancer of the discoloration of news.60 Age mainly takes amputation (amputation) treatment operation, however in the survival rate in 5 years also phase after patient's amputation When low, with the rapid progress of chemotherapy, cooperate the promotion of radiodiagnostics and surgical technic, the five of osteocarcinoma year deposit at present Motility rate has improved between 70~80%, and is expected to reach long-term survival (long-term survival), but still Merge the Treated with Chemotherapeutic Drugs object used when be unable to completely control, and treating, there are very strong myelosuppressive effects, therefore exploitation has The therapeutic agent of effect and Small side effects is to have its necessity for clinical application, for can both reduce on clinical treatment human bone cancer Drug is using concentration and reduces side effect, and up to preferable therapeutic effect.
R. alashanica is perennial acrophyta, has cold-resistant, drought-enduring plant, and inventor passes through biological library batch Amount screening, discovery R. alashanica have stronger degeneration-resistant ability, wherein there may be the substances for inhibiting cancer.
The drug for the treatment of osteocarcinoma is concentrated mainly on Chinese medicine composition and T-2 toxin at present, but these methods all can not What is avoided generates certain side effect to human body, and therapeutic effect is not unusual ideal.Therefore, it develops a kind of efficient , harmless drug seem extremely urgent.
Summary of the invention
For the above-mentioned prior art, the present invention provides a kind of new pharmaceutical compositions for treating osteocarcinoma.
A technical solution of the invention be it is a kind of for treating the pharmaceutical composition of osteocarcinoma, by ZLGAT polypeptide and Pharmaceutically acceptable carrier is constituted.Shown in the sequence of the polypeptide such as ZLGAT-1~25 are any, sequence is corresponded respectively to Shown in SEQ ID NO:1-25.
The present invention additionally provides a kind of preparation methods of polypeptide, this method comprises: weighing the whole rent strain of R. alashanica 100g is configured to the PBS aqueous solution that concentration of substrate is 5% after smashing to pieces, adjust pH to 8.0, trypsase 4000U/g blade is added, Hydrolysis temperature is 50 DEG C, and after digesting 90min, enzymolysis liquid is brought rapidly up to 90 DEG C, keeps 20min, carries out destroy the enzyme treatment.Then It is rapidly cooled to room temperature, 15min is being centrifuged with 3000r/min, is taking supernatant.According to 100 grams: 100ml ratio in wet macropore It adsorbs and tryptose enzymolysis liquid is added in resin DA201-C, 25 DEG C keep 180min, revolving speed 150r/min in constant-temperature table, use 75% ethanol solution elutes 120min, collects eluent in different time periods.The band for recycling small-molecular-weight, is obtained 103 The sequence of a small peptide.By verifying, wherein thering are 25 small peptides to have the function of that cancer cell is inhibited to be proliferated and killing cancer cell. According to the peak separation time different in chromatographic column, corresponding small peptide can be obtained in batches.Conventional, the polypeptide passes through people Work synthetic method can batch be used for industrialized application, avoid insufficient raw material, bring limitation.
In other embodiments, synergistic effect allows one or more other therapeutic agents and polypeptide of the invention to criticize Quasi- dosage combinations are given, but have and be higher than expected efficiency.
In a typical implementation, polypeptide is enough to allow with 0.2mg/kg to 20mg/kg intravenous administration with concentration Pharmaceutical composition exists.Include suitable for the peptide concentration in the composition and method in certain embodiments, still It is not limited thereto, at least about 0.2mg/kg, at least about 0.75mg/kg, at least about lmg/kg, at least about 2mg/kg, at least about 2.5mg/kg, at least about 3mg/kg, at least about 4mg/kg, at least about 5mg/kg, at least about 6mg/kg, at least about 7mg/kg, until Few about 8mg/kg, at least about 9mg/kg, at least about 10mg/kg, at least about llmg/kg, at least about 12mg/kg, at least about 13mg/ Kg, at least about 14mg/kg, at least about 15mg/kg, at least about 16mg/kg, at least about 17mg/kg, at least about 18mg/kg, at least About 19mg/kg, and at least about 20mg/kg.
Polypeptide can be given with single dose or multi-dose scheme.In general, polypeptide is in the period from about 1 hour to about 24 hours It inside gives, but was typically given within about 1 to 2 hour period.When dosage can repeat about 1 week to about 6 weeks or longer Between, 6 doses or more in total.Typically, dosage weekly, is repeated once every other week, or monthly, and minimum 6 Agent is to most 50 doses.
It can be oral administration, intravenous injection administration, subcutaneous administrations, administered intramuscular when administration.Benefit of the invention Myelodysplastic syndrome is treated with specific killing action of the polypeptide to cancer cell, acts on marrow and other hematopoiesis groups It knits, inhibits growth of tumour cell.There is good killing to osteocarcinoma and myeloproliferative disorder.
Specific embodiment
The present invention is further explained in the light of specific embodiments, these embodiments are merely to illustrate the present invention, and Do not limit the scope of the invention.
The acquisition of 1 polypeptide of embodiment
The whole strain 100g of R. alashanica is weighed, the PBS aqueous solution that concentration of substrate is 5% is configured to after smashing to pieces, adjusts pH extremely 8.0, trypsase 4000U/g blade is added, hydrolysis temperature is 50 DEG C, and after digesting 90min, enzymolysis liquid is brought rapidly up to 90 DEG C, 20min is kept, destroy the enzyme treatment is carried out.Then it is rapidly cooled to room temperature, 15min is being centrifuged with 3000r/min, is taking supernatant. Tryptose enzymolysis liquid is added in wet macroporous absorbent resin DA201-C according to 100 grams: 100ml ratio, 25 DEG C in constant-temperature table 180min, revolving speed 150r/min are kept, 120min is eluted with 75% ethanol solution, collects eluent in different time periods. The band for recycling small-molecular-weight, is obtained the sequence of 103 small peptides.By verifying, inhibit cancer thin wherein there are 25 small peptides to have Born of the same parents are proliferated and kill the function of cancer cell.The sequence of the polypeptide is as any shown such as ZLGAT-1~25 respectively, sequence point It Dui Yingyu not be shown in SEQ ID NO:1-25.
The preparation of 2 pharmaceutical composition of embodiment
0.03 part of ZLGAT-1 polypeptide, 1 part of starch, honey element or/and sucrose is taken to be used as sweetener, benzoic acid 0.1 in right amount Part, it mixes, crosses 50 meshes, after sterilizing, packaging.
The polypeptide of ZLGAT-2~29 is also all prepared into corresponding combination according to the preparation method of ZLGAT-1 polypeptide respectively Object.
The mixing of embodiment 3 pharmaceutical composition and other preparations
ZLGAT-1 polypeptide and bortezomib are mixed according to the ratio of 1:1, then using mixed drug weight as base Plinth number adds 1 part of starch, honey element or/and sucrose and is used as 0.1 part of sweetener, benzoic acid in right amount, mixes, and crosses 50 meshes, After sterilizing, packaging.
The detection of 4 drug safety of embodiment
According to the verification method of this field routine, it can be deduced that the present invention confirms safe and non-toxic, experiment knot through animal experiment Fruit is as follows with conclusion:
(1) acute toxicity testing shows: according to acute toxicity dose grading standard, belonging to practical nontoxicity grade；
(2) Micronucleus test, sperm malformation test, Salmonella reversion test result are feminine gender；
(3) 30 days feeding trials: experimental animal growing state is good, hematological examination, biochemical analysis, main dirty body ratio And histological indications are compared with the control group, are showed no exception, it was demonstrated that the present invention is safe and non-toxic.
The detection of 5 cytology level of embodiment
Myeloma cell strain XG7 is cultivated in the FCS-1640 complete culture solution of 100mL/L and (is contained HEPES25mol/L), every Day changes liquid, passes in time.Cell growth condition is detected using mtt assay, until cell grows into 3.0*108?.
Take 1ml, 3.0*108Cell, continue to cultivate in the FCS-1640 complete culture solution of 10ml, wherein in culture solution The pharmaceutical composition for being added to embodiment 2 and 3 respectively is subject to content of peptides additive amount as 0.2mg.Cell is carried out after culture 48h It counts, as a result as follows:
As can be seen from the above results, drug of the invention has effects that preferably to inhibit myeloma cell strain XG7.
Pharmaceutical activity experiment
(1) cell culture
Myeloma cell strain XG7 is cultivated in the FCS-1640 complete culture solution of 100mL/L and (is contained HEPES25mol/L), every Day changes liquid, passes in time.Cell growth condition is detected using mtt assay, until cell grows into 3.0*108?.
(2) preparation of Rat Model of Osteosarcoma
The myeloma cell strain XG7 of culture is collected, is cleaned 1 time, cell concentration is adjusted；It is subcutaneously big to SD on the outside of right hind Mouse is inoculated with 100ml cell suspension 0.5mL, 15 days after inoculation, 10 qualified SCID mices is taken to be randomly divided into two groups, in control group tumor 2ml physiological saline is injected, experimental group will be dissolved in the conjunction object of the drug of ethyl alcohol mixed liquor of normal saline according to 1.0mg/kg weight Dosage intratumor injection.It the 1st after administration, measures within 2,3,4,5 weeks tumour major diameter a and minor axis b weekly with vernier caliper, and calculates flat Equal diameter, i.e. r=(a+b)/2.After about 5 weeks, tumour can grow into suitable volume.Take the qualified SCID for having injected cell Mouse, control group intratumor injection 2ml physiological saline, experimental group will be dissolved in the pharmaceutical composition of ethyl alcohol mixed liquor of normal saline by According to the dosage intraperitoneal injection of 2.0mg/kg weight.0th, 10,20 day measurement subcutaneous transplantation tumor longest diameter (a) and vertical diameter after administration (d), tumour relative volume is calculated, the results are shown in Table 1 drug to the inhibiting effect (mm of Huppert's disease volume3)
As it can be seen from table 1 drug of the invention has the function of preferably inhibiting tumour growth, and can be significant Reduce the volume of tumour.The function of the growth for the inhibition tumour that it can be cooperateed with especially is administered in combination with bortezomib. The polypeptide of ZLGAT-2~25 can achieve identical with bortezomib administering drug combinations with ZLGAT-1 with bortezomib administering drug combinations Technical effect, specific value will not repeat them here.
Sequence table
110 > Cao Shuai of <
120 > of < is a kind of for treating the pharmaceutical composition of osteocarcinoma
〈160〉25
〈210〉1
〈211〉18
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-1
SMKWYVPNIIMLYNMPQF
〈210〉2
〈211〉18
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-2
MSIGVPGCSNLFGPCSLW
〈210〉3
〈211〉16
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-3
MFNIHMYAWLSECWWS
〈210〉4
〈211〉18
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-4
LNYESSLRLCSQHLDNHE
〈210〉5
〈211〉17
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-5
TTFYGPTSYHMGTPIGH
〈210〉6
〈211〉16
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-6
NYSVFQMYHSWWQWNS
〈210〉7
〈211〉18
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-7
EERILWIYDFLPRQMDCQ
〈210〉8
〈211〉17
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-8
GTALQSVTCTQHCWCGQ
〈210〉9
〈211〉18
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-9
PPRQIPLWRYIIFSQLWW
〈210〉10
〈211〉17
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-10
NTGAQRGDIREDYFRPV
〈210〉11
〈211〉18
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-11
FWPNCVPFGAPIWKWSSQ
〈210〉12
〈211〉18
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-12
FCARVSSQKGPRPAYLSR
〈210〉13
〈211〉17
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-13
WKRCEEGDASYLYRVAM
〈210〉14
〈211〉18
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-14
TRDMHAWFVNSKRDPHFC
〈210〉15
〈211〉16
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-15
QYHHCQTPWWRDDSMS
〈210〉16
〈211〉17
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-16
TMNADSEPDMGKSGEST
〈210〉17
〈211〉17
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-17
SQGDKHRQLAGMIKVIE
〈210〉18
〈211〉17
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-18
SSQKSHPQCCEAQENTW
〈210〉19
〈211〉17
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-19
AARDRCQPRVESGSCIL
〈210〉20
〈211〉14
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-20
QVVLGIEQPESKEV
〈210〉21
〈211〉13
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-21
GHDHQKIDLASWH
〈210〉22
〈211〉13
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-22
PYIMIQQQSDQPM
〈210〉23
〈211〉14
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-23
QRERQCKSWHYHYY
〈210〉24
〈211〉13
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-24
QRHAQAMGMRIEQ
〈210〉25
〈211〉14
〈212〉PRT
213 > artificial sequence of <
〈400〉ZLGAT-25
QIKKPWPNLHDRTD

Claims (4)

1. a kind of for treating the pharmaceutical composition of osteocarcinoma, characterized in that described pharmaceutical composition passes through following preparation method system It is standby: to take 0.01 part of polypeptide, 1 part of starch, appropriate sweetener, 0.1 part of benzoic acid, mix, cross 50 meshes, after sterilizing, packaging； The polypeptide is ZLGAT-1 polypeptide, and sequence is shown in SEQ ID NO:1；The sweetener is honey element or/and sucrose.
2. composition according to claim 1, characterized in that also addition bortezomib.
3. application of the described in any item pharmaceutical compositions of claim 1-2 in preparation for the drug of specific treatment osteocarcinoma.
4. a kind of polypeptide, characterized in that for sequence shown in SEQ ID NO:1.
CN201610143651.5A 2016-03-13 2016-03-13 It is a kind of for treating the pharmaceutical composition of osteocarcinoma Active CN105664134B (en)

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Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2860236B1 (en) * 2003-09-25 2006-01-06 Theraptosis PEPTIDES HAVING PARTICULARLY ANTI-ANGIOGENIC ACTIVITY AND THERAPEUTIC APPLICATIONS THEREOF
EP1629839A1 (en) * 2004-08-27 2006-03-01 Schwarz Pharma Ag Use of peptide compounds for treating bone cancer pain, chemotherapy- and nucleoside-induced pain
EP2172211B1 (en) * 2008-10-01 2014-12-03 Immatics Biotechnologies GmbH Composition of tumor-associated peptides and related anti-cancer vaccine for the treatment of glioblastoma (GBM) and other cancers
US20100297082A1 (en) * 2009-05-19 2010-11-25 Osteotech, Inc. Weight-bearing polyurethane composites and methods thereof
US8394922B2 (en) * 2009-08-03 2013-03-12 Medarex, Inc. Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof
US20120277158A1 (en) * 2009-10-06 2012-11-01 Angiochem Inc. Compositions and methods for the transport of therapeutic agents
WO2014160232A2 (en) * 2013-03-14 2014-10-02 The University Of Toledo Injectable biodegradable bone matrix for multiple myeloma lesion augmentation and osteoporosis
CN103505424B (en) * 2013-10-09 2015-03-11 哈药集团技术中心 Preparation method for bortezomib for injection
CN104288658A (en) * 2014-10-16 2015-01-21 济南新起点医药科技有限公司 Preparation method of fomes officinalis cough and asthma treating tablets and application of fomes officinalis cough and asthma treating tablets in preparation of medicine for inhibiting cell proliferation of mouse myeloma cell SP2/0
CN104547788A (en) * 2014-12-30 2015-04-29 丛培馥 Traditional Chinese medicine decoction for treating myeloproliferative disorder syndrome

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
小麦族鹅观草属植物研究进展;肖海峻等;《草业科学》;20070430;第24卷(第4期);41-46
李文克等.多发性骨髓瘤治疗的研究进展.《白血病•淋巴瘤》.2010,第19卷(第10期),637-640.

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