CN107137417A - One kind is used to treat cachectic pharmaceutical composition and its application - Google Patents
One kind is used to treat cachectic pharmaceutical composition and its application Download PDFInfo
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- CN107137417A CN107137417A CN201610115938.7A CN201610115938A CN107137417A CN 107137417 A CN107137417 A CN 107137417A CN 201610115938 A CN201610115938 A CN 201610115938A CN 107137417 A CN107137417 A CN 107137417A
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- ketorolac
- cytarabine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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Abstract
The present invention relates to the application of cytarabine or its analog and ketorolac or its analog in treatment cachexia, and specifically provide and a kind of can be used for treating cachectic pharmaceutical composition.The present invention it is creative first one or more of active components as composition in cytarabine or its analog and ketorolac or its analog are used for treatment of cachexia, surprising treatment curative effect is shown in zoopery.Based on cachectic order of severity, the present invention has wide potential applicability in clinical practice.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, and in particular to a kind of pharmaceutical composition containing cytarabine and ketorolac and application.
Background technology
The word of cachexia (cachexia) one derives from Hellenic " kakos " and " hexis ", literally means " severe situation ".(Cachexia as a major underestimated and unmet medical need：facts and numbers J Cachexia Sarcopenia Muscle(2010)1:1–5).Cachectic cardinal symptom includes weight loss, muscular atrophy, fatigue and weak, poor appetite.The definition of cachexia medically be can not by have additional nutrients the body weight loss that can be reversed and human body it is weak.Cachexia is common in cancer, AIDS, septicemia, severe trauma, chronic obstructive pulmonary disease, multiple sclerosis, congestive heart failure, pulmonary tuberculosis, familial amyloid polyneuropathy, chronic kidney disease, cystic fibrosis, type i diabetes and other gradual chronic disease (Biology of Cachexia, J Natl Cancer Inst (1997) 89 (23):1763-1773；Cancer cachexia, mechanism and treatment, World J Gastrointest Oncol.2015 Apr 15；7(4):17–2).Cachexia is to can result in patient death hazards, it means that cachexia once occur in these patients, and dead possibility will be dramatically increased.According to the literature, 30% it is directly to die from cachexia in cancer patient, rather than dies from tumour occupy-place.Except directly till death in addition to, cachexia is once to occur influence to patient very serious.Cachexia not only causes patient body rapid weak until losing self care ability, can also seriously reduce reaction and tolerance of the above-mentioned patient to standard care.According to statistics, all there are cachectic symptoms in 80% patients with advanced cancer, and greatly pain and pressure are brought to patient extremely family members.Once there is serious cachexia in cancer patient, just represents patient and enters whole latter stage.The therapeutic strategy of cancer patient will be changed to based on palliative treatment, and the life span of patient can be with week calculating.Except cancer, cachexia also has very high incidence with COPD Patients.Because the radix of COPD Patients is huge, the cachectic COPD Patients number of generation is very big, and only the U.S. is with regard to patient as 3,200,000.According to the literature, worldwide 1% population is perplexed by cachexia, in Europe, North America and the cachectic persons for originally having more than 9,000,000 day.Because current clinic there is no for cachectic active drug, cachectic patient's number is directly died from Europe, North America and day 7,400,000 are originally reached.Therefore, cachexia is a very serious clinical problem, while there is a huge unsatisfied clinical demand on treatment of cachexia.
The treatment means used for cachexia clinical at present are mainly to improve based on nutrition and relief of symptoms.The medicine used at present mainly has ethisterone (including megestrol acetate and medroxyprogesterone acetate) and corticosteroid (including dexamethasone, methylprednisolone and prednisolone).Clinical Evidence shows that megestrol acetate and medroxyprogesterone acetate can improve appetite, calorie intake and nutritional status, but increased body weight is main based on fat.The life quality of patient and life cycle are not extended significantly.There is certain side effect, including the increase of thromboembolism, edema of limbs, hypertension, hyperglycemia, cushing's syndrome, adrenal function suppression and adrenal gland function deficiency simultaneously.Corticosteroid can increase patient's appetite and allow patient to produce good feel.But these effects were only limited within several weeks.Due to the apparent side effect of long-term treatment and they are shorter to cachectic acting duration, they are more suitable for being expected the shorter patient of life span, and wherein increased weight effect is not obvious, and patient's life cycle is not extended.Therefore, current urgent clinical needs can improve cachectic persons' life quality, and the active drug of patient's life cycle can be improved again.
The content of the invention
The first object of the present invention is to provide the application of cytarabine or its analog in treatment cachexia medicine is prepared.
Cytarabine is a kind of miazines nucleoside analog, by suppressing the synthesis of cell DNA, the propagation of interference cell.Nineteen fifty-nine is equal to by the Richard Walwick of Berkeley earliest artificial synthesized.Cytarabine is mainly used in acute leukemia, including acute myeloblastic leukemia and ALL, is also used for lymthoma.It is wherein best to acute myeloblastic leukemia effect, but cytarabine or its analog have no report for treatment of cachexia.
Cachexia of the present invention can be by tumour, AIDS, septicemia, severe trauma, chronic obstructive pulmonary disease, multiple sclerosis, congestive heart failure, pulmonary tuberculosis, familial amyloid polyneuropathy, chronic kidney disease, cystic fibrosis, type i diabetes and other gradual chronic diseases etc. are induced.Preferably, cachexia of the present invention is by tumor inducing, such as cancer of pancreas, lung cancer, stomach cancer and colorectal cancer.
Cytarabine analog of the present invention includes officinal salt, solvate, hydrate, stereoisomer, inclusion compound or prodrug of cytarabine etc..The ketorolac analog is officinal salt, solvate, hydrate, stereoisomer, inclusion compound or the prodrug of ketorolac.
Pharmaceutically acceptable cytarabine salt of the above-mentioned cytarabine officinal salt including cytarabine hydrochloride；Solvate refers to the solvate containing above-mentioned effective component；Hydrate refers to the aquo-compound of above-mentioned active ingredient；Inclusion compound refers to the inclusion compound containing above-mentioned active ingredient；Its prodrug includes reacting the compound for generating above-mentioned active ingredient in vivo.Cytarabine prodrug includes but is not limited to valyl cytarabine, cytarabine derivative of fatty acid CP-4055, cytarabine phosphoramidate, Astarabine (cytarabine and aspartoyl covalent conjunct agent) etc., preferable cytarabine analog such as cytarabine hydrochloride.
Present inventors have unexpectedly found that cytarabine or its analog individually can be used for treatment of cachexia, it can be in the case where not influenceing tumour growth, improve cachexia mouse health status and extension cachexia survival time of mice, the above results show it for treatment of cachexia, with significant activity.
The second object of the present invention is to provide ketorolac or its analog, or ketorolac or its analog combine the application in treatment cachexia medicine is prepared with cytarabine or its analog.
Ketorolac is the derivative of pyrrole acid, belongs to NSAIDs, suppresses PG synthesis, with analgesia, anti-inflammatory, refrigeration function and suppression platelet aggregation.The short that current clinically ketorolac is mainly used in various pain includes Acute skeletal muscle pain caused by various postoperative pains (such as the postoperative pain such as belly, chest, urological department, gynaecology, the department of stomatology, orthopedic) and a variety of causes, such as sprain, misplace, fracturing and soft tissue injury, and pain caused by other diseases such as afterpains, acute renal colic, toothache, sciatica, ache in late cancer, wound pain, cholecystalgia etc., can as morphine, pethidine substitute.
At present, on ketorolac or its analog, for treatment of cachexia, there is not been reported with research.
Ketorolac analog of the present invention is officinal salt, solvate, hydrate, stereoisomer, inclusion compound or the prodrug of ketorolac.
Ketorolac officinal salt of the above-mentioned ketorolac officinal salt including ketorolac tromethamine；Solvate refers to the solvate containing above-mentioned effective component；Hydrate refers to the aquo-compound of above-mentioned active ingredient；Inclusion compound refers to the inclusion compound containing above-mentioned active ingredient；Its prodrug includes reacting the compound for generating above-mentioned active ingredient in vivo.The prodrug of ketorolac includes but is not limited to galactosyl ketorolac, ketorolac Arrcostab, ketorolac piperazine alkyl ester, ketorolac acid amides etc..Wherein, preferred ketorolac tromethamine.
It individually can be used for treatment of cachexia present invention demonstrates ketorolac or its analog, its life quality that can put on weight and improve illustrates that ketorolac or its analog can effectively be alleviated to symptom caused by cachexia.
Further, the present invention is it has been unexpectedly discovered that when above two active component (cytarabine or its analog and ketorolac or its analog) is combined, the two realizes significant cooperative effect, can more desirably be applied to treatment of cachexia.
The third object of the present invention is to provide a kind of brand-new pharmaceutical composition, to fill up the clinical blank for still lacking effective cachexia medicine at present.
To achieve the above object, the present invention is adopted the following technical scheme that：
A kind of pharmaceutical composition, its active component is made up of the one or more of cytarabine or its analog and ketorolac or its analog, is preferably made up of a kind of one kind with ketorolac or its analog in cytarabine or its analog.
Specifically, aforementioned pharmaceutical compositions, one or more that can be individually using cytarabine or its analog are used as active component, individually it can also be each combined with ketorolac or its analog using one or more therein as active component, or cytarabine or its analog using ketorolac or the one or more of of its analog and be used as active component.
Inventor has found in research process, when the two is combined, the mole dosage of the two produces influence than the degree changed for cooperative effect, and further investigation on this basis shows, the mol ratio of the cytarabine or its analog and ketorolac or its analog is 154.8~0.8：1.It in above-mentioned amount ranges, can maximize the cooperative effect of the two.Wherein, preferably the mol ratio of the two is 30~1.5:1.
It is desirable that the active component in described pharmaceutical composition is is made up of cytarabine and ketorolac tromethamine, the mol ratio of the two is 30~1.5:1 is advisable, and preferably 6~1.5:1.
Further, total content of the above-mentioned active component in described pharmaceutical composition is 0.5~50%, preferably 1~20%.
In addition to the active ingredient (s, pharmaceutical composition of the present invention still further comprises pharmaceutically acceptable auxiliary material to be prepared into particular dosage form." pharmaceutically acceptable auxiliary material " herein is understood that the different dosage forms that can be prepared according to needs are to select suitable auxiliary material type, and specially those skilled in the art are grasped, and the present invention is not particularly limited to this by those skilled in the art.
Pharmaceutical composition of the present invention is preferably oral formulations, scalp absorbent or ejection preparation etc., the oral formulations preferred tablet, granule, syrup；The preferred freeze drying powder injection of ejection preparation or parenteral solution.
Invention also provides application of the aforementioned pharmaceutical compositions in treatment cachexia medicine is prepared.
Cachexia of the present invention can be by tumour, AIDS, septicemia, severe trauma, chronic obstructive pulmonary disease, multiple sclerosis, congestive heart failure, pulmonary tuberculosis, familial amyloid polyneuropathy, chronic kidney disease, cystic fibrosis, type i diabetes and other gradual chronic diseases etc. are induced.
Especially, aforementioned pharmaceutical compositions are preparing treatment, the tumour preferred cancer of pancreas, lung cancer, stomach cancer and colorectal cancer more notable by cachectic application effect of tumor inducing.That is, pharmaceutical composition of the present invention for being protruded the most as the cachexia therapeutic effect caused by above-mentioned several tumours.
The present invention it is creative first by the use of cytarabine or its analog and ketorolac or its analog as the active component of composition, for treating cachexia, particularly for treating the cachexia by tumor inducing, generate unexpected effect.
Pharmaceutical composition of the present invention has reversed cachectic process in the case where not influenceing tumour growth, completely, and mouse health status is completely recovered to normal condition, reaches cachectic healing state, and life cycle is greatly extended.Due to the very big extension of life cycle, the tumor load at the end for the treatment of group can reach 2 times when control group is dead, it is seen that cachectic new tool can be treated not by not suppressing tumour growth the invention provides one kind.
The active component of pharmaceutical composition of the present invention is known compound, can be bought from raw material pharmaceutical factory, and such as cytarabine is purchased from Wuhan far into Science and Technology Ltd. is created, and ketorolac tromethamine is purchased from Hubei Ju Sheng Science and Technology Ltd.s etc..
The present invention it is creative first cytarabine or its analog and ketorolac or its analog as composition are used for treatment of cachexia, surprising treatment curative effect is shown under study for action.The curative effect of said composition exceed the medicine of current Clinical practice and reported for work grinding medicine for cachectic.Based on cachectic order of severity, the present invention has wide potential applicability in clinical practice.
Embodiment
Embodiment 1
The active component present embodiments provided in a kind of pharmaceutical composition, described pharmaceutical composition is：Cytarabine and ketorolac, the mass ratio of the two are 1.5：1.
Embodiment 2
The active component present embodiments provided in a kind of pharmaceutical composition, described pharmaceutical composition is：Cytarabine and ketorolac tromethamine, the mass ratio of the two are 3：1.
Embodiment 3
The active component present embodiments provided in a kind of pharmaceutical composition, described pharmaceutical composition is：Cytarabine hydrochloride and ketorolac, the mass ratio of the two are 3：1.
Embodiment 4
The active component present embodiments provided in a kind of pharmaceutical composition, described pharmaceutical composition is：Cytarabine hydrochloride and ketorolac tromethamine, the mass ratio of the two are 4.5：1.
Embodiment 5
A kind of pharmaceutical composition is present embodiments provided, described pharmaceutical composition is parenteral solution, and the specific prescription of the parenteral solution is：The parts by weight of cytarabine 20, the parts by weight of ketorolac tromethamine 10, the parts by weight of solubilizer poloxamer 2, the parts by weight of isotonic regulator sodium chloride 15, appropriate pH adjusting agent (adjusting pH value to 7.0-7.4), the parts by weight of water for injection 50.
Embodiment 6
A kind of pharmaceutical composition is present embodiments provided, described pharmaceutical composition is freeze drying powder injection, and the specific prescription of the freeze drying powder injection is：The parts by weight of cytarabine 30, the parts by weight of ketorolac tromethamine 10, the parts by weight of excipient mannitol 20, C3 parts of antioxidant vitamin, appropriate pH adjusting agent (adjusting pH value to 7.0-7.4).
The preparation method of the present embodiment simultaneously there is provided above-mentioned freeze drying powder injection：The active component and excipient of above-mentioned recipe quantity are weighed, is dissolved in the water for injection of recipe quantity, then stirring to complete solvent adds the antioxidant of recipe quantity, and adjust pH value to 7.0-7.4 with the pH value regulator of recipe quantity.Medical filtration is degerming, it is filling in vial.After freeze-drying, sealing is produced.
Except the above-mentioned implementation exception enumerated, it will be appreciated by those skilled in the art that ground is, in the range of the present invention advocates, those skilled in the art are combined cytarabine or its analog and ketorolac or its analog in a variety of manners, or according to conventional formulation general knowledge, various pharmaceutical preparations can be prepared to realize the present invention, this is repeated no more.
Effect of the experimental example 1 to mouse weight
Curative effect involved by this experimental example is carried out on C26 colon cancer cachexia animal models.C26 colon cancer cachexia models are the cancer cachexia animal models of Global Access, are widely adopted in anti-cachexia medicament screening experiment.The model can cause the Body weight loss and human body of the Fast Persistence of similar patients with advanced cancer generation weak until death.
The foundation of model uses female BAl BIc/C mice of about 20 grams of body weight, using the C26 tumour cells of subcutaneous vaccination 500,000.More than 5% as cachexia standard occurs for mouse weight.
Experiment reagent：
Control group：Physiological saline
Cytarabine group：Cytarabine concentration is 3mg/ml normal saline solution；
Composition group：Cytarabine and ketorolac tromethamine solution, wherein, the concentration of cytarabine is 3mg/ml, and the concentration of ketorolac tromethamine is 1mg/ml；
Above-mentioned experiment reagent is placed in 4 DEG C of refrigerators and preserves stand-by after preparing.
Experimental method：
Morbidity mouse is divided into 3 groups, respectively saline control group (n=7), cytarabine group (n=8) and composition group (n=8).Cytarabine group gives hypodermic injection cytarabine solution 0.1ml, and composition group gives hypodermic injection cytarabine and ketorolac tromethamine mixture solution 0.1ml.
Tight tracking mouse health status and changes of weight during experiment.
Experimental result：
This experimental example experimental result is as shown in table 1.Although the 3rd day after being discontinued, the mouse weight and control group of cytarabine group and composition group compare, and all significantly improve (p<0.05), but the 3rd administration same day, cytarabine group mouse weight decline it is obvious, and composition group mouse weight then rise substantially (<0.05), illustrate that cytarabine has the side effect for aggravating the state of an illness, and ketorolac tromethamine can offset this side effect, the effect with obvious attenuation synergistic.All it is urgent patient in view of occurring cachectic patient, the side effect of very little is likely to produce fatal consequence, highlights the meaning of this composition invention.
Table 1
* p is compared with control group<0.05.
Influence of the experimental example 2 to survival time of mice
Control group：Physiological saline
Ketorolac tromethamine group：Ketorolac tromethamine concentration is 1mg/ml normal saline solution；
Composition group：Cytarabine and ketorolac tromethamine solution, wherein, the concentration of cytarabine is 3mg/ml, and the concentration of ketorolac tromethamine is 1mg/ml；
Above-mentioned experiment reagent is placed in 4 DEG C of refrigerators and preserves stand-by after preparing.
Experimental method：
Morbidity mouse is divided into three groups, respectively saline control group, ketorolac group and composition group.Wherein, ketorolac group gives mouse subcutaneous injection ketorolac tromethamine solution 0.1ml, and composition group gives the physiological saline mixture solution 0.1ml of mouse subcutaneous injection ketorolac tromethamine and cytarabine.The life span of each group mouse is kept track of after administration, control group and each treatment group are respectively compared with t test.
Experimental result：
As a result as shown in table 2, composition treatment group survival time of mice extension, with control group comparing difference significantly (p<0.05).And the life cycle of ketorolac tromethamine treatment group and control group compare, difference does not have statistical significance (p>0.05).
Table 2
| Mouse number of elements | Life span (my god) | P value | |
| Control group | 7 | 34.00±4.392 | |
| Ketorolac group | 8 | 37.00±3.632 | 0.060 |
| Composition group | 8 | 44.63±0.3750 | 0.023 |
Effect of the experimental example 3 to mouse tumor
Experiment reagent and experimental method are with experimental example 1.
Experimental result (refers to table 3)：
Since after tumor inoculation the 7th day, with two maximum gauges of vernier caliper measurement tumour, measure 2 times weekly.Tumor size cartographic represenation of area (mm2).As shown in table 3, no matter cytarabine, or composition, to the growth of tumour all without inhibitory action.Opposite to occur due to cachectic, control group mice tumour growth seems slack-off, although and treatment group's comparing difference does not have statistical significance.This phenomenon illustrates that cytarabine and composition are produced to treatment of cachexia effect not by tumour growth is suppressed, but passes through a kind of new unknown mechanism of action.
Table 3
Although the present invention, those skilled in the art is described in detail with most preferred embodiment above it is to be understood that on the premise of without departing from inventive concept and spirit, any improvement and modification made to the present invention are still fallen within the scope of protection of present invention.
Claims (10)
1. the application of cytarabine or its analog in treatment cachexia medicine is prepared.
2. ketorolac or its analog, or ketorolac or its analog and cytarabine or its class
The application in treatment cachexia medicine is prepared is closed like Internet of Things.
3. a kind of pharmaceutical composition, it is characterised in that：Its active component by cytarabine or its
One or more of compositions of analog and ketorolac or its analog, preferably by cytarabine or its
A kind of composition of a kind of and ketorolac or its analog in analog.
4. pharmaceutical composition according to claim 3, it is characterised in that the arabinose born of the same parents
Mol ratio associated with glycosides or its analog and ketorolac or its analog is 154.8~0.8：1.
5. the pharmaceutical composition according to claim 3 or 4, it is characterised in that the Ah
Sugared cytidine analog is the officinal salt of cytarabine, solvate, hydrate, alloisomerism
Body, inclusion compound or prodrug；The ketorolac analog is the officinal salt of ketorolac, solvation
Thing, hydrate, stereoisomer, inclusion compound or prodrug；It is preferred that ketorolac tromethamine.
6. the pharmaceutical composition according to claim any one of 3-5, it is characterised in that institute
State pharmaceutical composition and further comprise pharmaceutically acceptable auxiliary material.
7. pharmaceutical composition according to claim 6, it is characterised in that the medicine group
Compound is oral formulations or ejection preparation.
8. pharmaceutical composition according to claim 7, it is characterised in that the oral system
Agent is tablet, granule, syrup；The ejection preparation is freeze drying powder injection or parenteral solution.
9. any one of claim 3-8 described pharmaceutical composition is in treatment cachexia medicine is prepared
Application.
10. the application according to any one of claim 1,2 or 9, it is characterised in that：Institute
Cachexia is stated by tumor inducing, the preferred cancer of pancreas of tumour, lung cancer, stomach cancer and colorectal cancer.
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| CN201610115938.7A CN107137417B (en) | 2016-03-01 | 2016-03-01 | Pharmaceutical composition for treating cachexia and application thereof |
| PCT/CN2016/099329 WO2017148129A1 (en) | 2016-03-01 | 2016-09-19 | Pharmaceutical composition for treating cachexia and use thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2019136739A1 (en) * | 2018-01-15 | 2019-07-18 | Yinuoke Medicine Science And Technology Company Ltd. | Treatments for cachexia |
| CN115279367A (en) * | 2020-02-24 | 2022-11-01 | 长春亿诺科医药科技有限责任公司 | Compositions and methods for treating cytokine storm and cytokine release syndrome |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2747528C2 (en) | 2015-12-03 | 2021-05-06 | Биосайт Лтд. | Conjugate salts for cancer treatment |
| US12071450B2 (en) | 2015-12-03 | 2024-08-27 | Biosight Ltd. | Salts of conjugates for cancer therapy |
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| WO2008144880A1 (en) * | 2007-05-31 | 2008-12-04 | F.P.L. Pharma Inc. | Compositions for prevention or treatment of anorexia-cachexia syndrome and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101167722A (en) * | 2007-10-22 | 2008-04-30 | 鲁南制药集团股份有限公司 | Ketorolac tromethamine freezing-dried power injection and preparation method thereof |
| CN101787064A (en) * | 2009-01-23 | 2010-07-28 | 高峰 | Cytarabine prodrug derivatives and purposes thereof in resisting cancers and tumors |
| CN105343094A (en) * | 2015-11-17 | 2016-02-24 | 王丽 | Pharmaceutical composition resisting cancer cell migration |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019136739A1 (en) * | 2018-01-15 | 2019-07-18 | Yinuoke Medicine Science And Technology Company Ltd. | Treatments for cachexia |
| GB2571849A (en) * | 2018-01-15 | 2019-09-11 | Yinuoke Medicine Science And Tech Company Ltd | Treatments for cachexia |
| GB2571849B (en) * | 2018-01-15 | 2020-05-20 | Yinuoke Medicine Science And Tech Company Ltd | Treatments for cachexia |
| CN111655341A (en) * | 2018-01-15 | 2020-09-11 | 长春亿诺科医药科技有限责任公司 | For the treatment of cachexia |
| EP3740287A4 (en) * | 2018-01-15 | 2021-11-03 | Yinuoke Medicine Science And Technology Company Ltd. | Treatments for cachexia |
| US12059427B2 (en) | 2018-01-15 | 2024-08-13 | Yinuoke Medicine Science And Technology Company Ltd. | Treatments for cachexia |
| CN115279367A (en) * | 2020-02-24 | 2022-11-01 | 长春亿诺科医药科技有限责任公司 | Compositions and methods for treating cytokine storm and cytokine release syndrome |
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| CN107137417B (en) | 2021-02-19 |
| WO2017148129A1 (en) | 2017-09-08 |
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