CN108042792A - The applications of CD61 in treatment medication for treating pyemia is prepared and combinations thereof - Google Patents

The applications of CD61 in treatment medication for treating pyemia is prepared and combinations thereof Download PDF

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Publication number
CN108042792A
CN108042792A CN201711459727.6A CN201711459727A CN108042792A CN 108042792 A CN108042792 A CN 108042792A CN 201711459727 A CN201711459727 A CN 201711459727A CN 108042792 A CN108042792 A CN 108042792A
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Prior art keywords
cooled
dried powder
freeze dried
stabilizer
pharmaceutical composition
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Chinese (zh)
Inventor
孙炳伟
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Nanjing Dong No Medical Science And Technology Development Co Ltd
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Nanjing Dong No Medical Science And Technology Development Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177Receptors; Cell surface antigens; Cell surface determinants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention discloses CD61 or its segment to prepare for treating the application in medication for treating pyemia, which has certain pyemic effect for the treatment of.The invention also discloses pharmaceutical composition and its freeze dried powder containing CD61, said composition and its freeze dried powder effectively mitigate septicopyemia symptom, and new research direction is provided for treatment pyemia field.

Description

The applications of CD61 in treatment medication for treating pyemia is prepared and combinations thereof
Technical field
The invention belongs to treat the technical field of inflammatory conditions, and in particular to CD61 is in treatment medication for treating pyemia is prepared Using and combinations thereof.
Background technology
Pyemia (Sepsis) is common complication after severe trauma, shock and infection, and further development can cause purulence Toxicogenic shock, multiple organ dysfunction syndrome (MODS), even if high on basis and clinic study and Intensive Care Therapy means The modern times of development are spent, clinical treatment still produces little effect, and the death rate remains high!Pyemia is inflammatory reaction and Activated Coagulation Important stimulus factor, there are apparent cross reactions between Activated Coagulation and inflammatory reaction.
During research shows that platelet activation participates in coagulation system activation, the membrane glycoprotein and regulatory factor on surface Play very crucial effect.Wherein early-stage study is found, membrane glycoprotein CD61 has a pyemic effect of blocking, therefore there is an urgent need for That researches and develops a kind of effective dose treats pyemic autologous drug.
The content of the invention
In view of the problems of the above-mentioned prior art, the purpose of the present invention is to propose to a kind of CD61 to prepare treatment pyemia Application in drug.The CD61 has certain pyemic effect for the treatment of.
The purpose of the present invention will be achieved by the following technical programs:
CD61 or its segment are preparing for treating the application in medication for treating pyemia.
Above-mentioned application, wherein, the drug is oral drugs.
Above-mentioned application, wherein, the CD61 is formulated into including forming drug in one or more excipient or stabilizer Composition.
Above-mentioned application, wherein, described pharmaceutical composition is freeze-dried powder form.
It is a further object to provide a kind of pharmaceutical compositions containing CD61.Said composition can effectively mitigate Septicopyemia symptom.
For one kind for treating pyemic pharmaceutical composition, described pharmaceutical composition includes CD61 or its segment, Yi Zhonghuo A variety of excipient or stabilizer.
It is a kind of to be prepared into freeze dried powder according to aforementioned pharmaceutical compositions.
Above-mentioned freeze dried powder, wherein, it is freezed and is made by the component of following parts by weight:10-28 parts of CD61 or its segment are assigned 400-800 parts of shape agent, 1-1.5 parts of stabilizer, 9170-9590 parts of water for injection.
Above-mentioned freeze dried powder, wherein, the excipient is one kind or its combination in mannitol, gelatin or sucrose;Institute Stabilizer is stated as one kind in glutathione, serine or sucrose or its combination.
A kind of preparation method of freeze dried powder, includes the following steps:Membrane glycoprotein, excipient, stabilizer are dissolved in note Penetrate with water, mix, filter, packing, precooling, vacuum drying to get.
A kind of preparation method of above-mentioned freeze dried powder, wherein, the precooling includes the following steps:It is cooled to 4 DEG C, it is cold 1h-2h is hidden, is cooled to 0 DEG C~-10 DEG C, freezes 2h~3h;- 25 DEG C~-30 DEG C are cooled to, freezes 1h~3h;It is cooled to -45 DEG C ~-55 DEG C, freeze 2h~4h.
Compared with prior art, applications and its group of a kind of CD61 provided by the invention in treatment medication for treating pyemia is prepared Object is closed, what is reached has the technical effect that:The CD61 of the present invention has treatment pyemia, and is prepared into drug, is taken for human body, New research direction is provided for treatment pyemia field;Freeze dried powder prepared by the present invention is suitable for oral, you can effectively Mitigate septicopyemia symptom.
Below just in conjunction with the embodiments, the embodiment of the present invention is described in further detail, so that technical solution is more It should be readily appreciated that, grasp.
Specific embodiment
Below by specific embodiment, the present invention will be described, but the present invention is not limited thereto.In following embodiments The experimental method is conventional method unless otherwise specified;The reagent and material, unless otherwise specified, can be from business Approach obtains, and example below is not to limit the scope of the claims of the present invention, all equivalence enforcements without departing from carried out by the present invention Or change, it is intended to be limited solely by the scope of this patent.
Embodiment 1
CD61 freeze dried powder formulas
CD61 1.2g, mannitol 45g, glutathione 0.15g, water for injection 953.65g.
Preparation method:
By CD61 1.2g, mannitol 45g, glutathione 0.15g is dissolved with appropriate water for injection, continues to add water for injection To 1000g, 0.22 μm of membrane filtration degerming is sub-packed in 1ml/ branch in cillin bottle;
Cillin bottle after packing is subjected to precooling:4 DEG C are first cooled to, refrigerates 1h, is cooled to 0 DEG C, freezes 2h;Cooling To -25 DEG C, 1h is freezed;Be cooled to -45 DEG C, freezing 2h to get;
By after precooling cillin bottle be dried in vacuo to get.Wherein, the CD61 in the present embodiment can be selected its segment and replace Generation.
Embodiment 2
CD61 freeze dried powder formulas
CD61 1g, gelatin 40g, serine 0.1g, water for injection 958.9g.
Preparation method:
By CD61 1g, gelatin 40g, serine 0.1g is dissolved with appropriate water for injection, continues to inject water to 1000g, 0.22 μm of membrane filtration degerming, is sub-packed in 1ml/ branch in cillin bottle;
Cillin bottle after packing is subjected to precooling:4 DEG C are first cooled to, refrigerates 1.5h, is cooled to -2 DEG C, freezes 2.5h; - 25 DEG C DEG C are cooled to, freezes 1h;Be cooled to -48 DEG C, freezing 2.5h to get;
By after precooling cillin bottle be dried in vacuo to get.
Embodiment 3
CD61 freeze dried powder formulas
CD61 1.5g, sucrose 61g, serine 0.12g, water for injection 937.38g.
Preparation method:
By CD61 1.5g, sucrose 61g, serine 0.12g is dissolved with appropriate water for injection, continues to inject water to 1000g, 0.22 μm of membrane filtration degerming, is sub-packed in 1ml/ branch in cillin bottle;
Cillin bottle after packing is subjected to precooling:4 DEG C are first cooled to, refrigerates 1h, is cooled to -8 DEG C, freezes 2h;Cooling To -28 DEG C, 2h is freezed;Be cooled to -50 DEG C, freezing 3h to get;
By after precooling cillin bottle be dried in vacuo to get.
Embodiment 4
CD61 freeze dried powder group of formula
CD61 1.0g, sucrose 60g, gelatin 12g, serine 0.13g, water for injection 926.87g.
Preparation method:
CD61 1.0g, sucrose 60g, gelatin 12g, serine 0.13g with appropriate water for injection are dissolved, continues filling and penetrates With water to 1000g, 0.22 μm of membrane filtration degerming is sub-packed in 1ml/ branch in cillin bottle;
Cillin bottle after packing is subjected to precooling:4 DEG C are first cooled to, refrigerates 2h, is cooled to -10 DEG C, freezes 3h;Cooling To -25 DEG C, 3h is freezed;Be cooled to -55 DEG C, freezing 4h to get;
By after precooling cillin bottle be dried in vacuo to get.
Embodiment 5
CD61 freeze dried powder formulas
CD61 1.4g, sucrose 48g, glutathione 0.12g, water for injection 950.48g.
By CD61 1.4g, sucrose 48g, glutathione 0.12g is dissolved with appropriate water for injection, continues to inject water to 1000g, 0.22 μm of membrane filtration degerming, is sub-packed in 1ml/ branch in cillin bottle;
Cillin bottle after packing is subjected to precooling:4 DEG C are first cooled to, refrigerates 1h, is cooled to -3 DEG C, freezes 2h;Cooling To -28 DEG C, 1h is freezed;Be cooled to -45 DEG C, freezing 4h to get;
By after precooling cillin bottle be dried in vacuo to get.
Control group 1
CD61 0.8g, mannitol 45g, glutathione 0.15g, water for injection 954.05g.
By CD61 0.8g, mannitol 45g, glutathione 0.15g is dissolved with appropriate water for injection, continues to add water for injection To 1000g, 0.22 μm of membrane filtration degerming is sub-packed in 1ml/ branch in cillin bottle;
Cillin bottle after packing is subjected to precooling:4 DEG C are first cooled to, refrigerates 1h, is cooled to -3 DEG C, freezes 2h;Cooling To -28 DEG C, 1h is freezed;Be cooled to -45 DEG C, freezing 4h to get;
By after precooling cillin bottle be dried in vacuo to get.
Control group 2
CD61 0.1g, mannitol 45g, glutathione 0.15g, water for injection 954.75g.
By CD61 0.1g, mannitol 45g, glutathione 0.15g is dissolved with appropriate water for injection, continues to add water for injection To 1000g, 0.22 μm of membrane filtration degerming is sub-packed in 1ml/ branch in cillin bottle;
Cillin bottle after packing is subjected to precooling:4 DEG C are first cooled to, refrigerates 1h, is cooled to -45 DEG C, freezes 4h, i.e., ;
By after precooling cillin bottle be dried in vacuo to get.
Test example
Experimental procedure:
Material:SPF grades of SD male mices, weight 20 ± 2g, are divided into 9 groups by 90, every group 10, be respectively normal group, Model group, embodiment 1-5 groups, control group 1-2.
Normal group is fed for chow diet, gives distilled water 0.1ml/20g;
Model group, embodiment 1-5 groups, control group 1-2 are first 2 days intraperitoneal injection LPS 40mg/kg, are opened within subsequent 3rd day Beginning, model group continues to give distilled water 0.1ml/20g in 5 days,;
Embodiment 1-5 groups, control group 1-2 start to give within lasting 5 days its freeze-dried 0.1ml/ of CD61 prepared by correspondence on the 3rd day 20g。
First 3 days it is every 12 it is small when mouse of observation state and activity, latter 5 days it is every 6 it is small when observe the state of a mouse And activity, and count the survival rate of every group of mouse.It the results are shown in Table 1.
The freeze-dried pyemic influences on LPS inductions of 1 CD61 of table
After when LPS intraperitoneal injections 12 are small, 90% mouse appearance is slow in reacting, and activity and feed are reduced, and secretion increases Symptom;15 it is small when after, all mouse occur it is slow in reacting, activity and feed reduce, the symptom that secretion increases;48 is small When, then the above-mentioned symptom of mouse aggravates, then the success using the state of mouse at this time as model manufacturing.
CD61 has pyemic effect for the treatment of as shown in Table 1, and CD61 freeze dried powders treatment LPS prepared by the present invention is lured The effect for leading mouse sepsis has significant difference, has certain therapeutic effect;Optimum weight part of CD61 in the present invention For 10-28 parts, and optimal precooling condition refrigerates 1h-2h to be cooled to 4 DEG C, is cooled to 0 DEG C~-10 DEG C, and freezing 2h~ 3h;- 25 DEG C~-30 DEG C are cooled to, freezes 1h~3h;- 45 DEG C~-55 DEG C are cooled to, freezes 2h~4h.
Several preferred embodiments of the present invention have shown and described in above description, but as previously described, it should be understood that the present invention Be not limited to form disclosed herein, be not to be taken as the exclusion to other embodiment, and available for various other combinations, Modification and environment, and above-mentioned introduction or the technology or knowledge of association area can be passed through in the scope of the invention is set forth herein It is modified.And changes and modifications made by those skilled in the art do not depart from the spirit and scope of the present invention, then it all should be in this hair In the protection domain of bright appended claims.

Claims (10)

1.CD61 or its segment are preparing for treating the application in medication for treating pyemia.
2. according to the application described in claim 1, which is characterized in that the drug is oral drugs.
3. according to the application described in claim 2, which is characterized in that the CD61 is formulated into including one or more figurations Pharmaceutical composition is formed in agent or stabilizer.
4. according to the application described in claim 3, which is characterized in that described pharmaceutical composition is freeze-dried powder form.
5. one kind is used to treat pyemic pharmaceutical composition, which is characterized in that described pharmaceutical composition includes CD61 or its piece Section, one or more excipient or stabilizer.
6. a kind of pharmaceutical composition according to claim 5 is prepared into freeze dried powder.
7. freeze dried powder according to claim 6, which is characterized in that freezed and be made by the component of following parts by weight:CD61 Or 10-28 parts of its segment, 400-800 parts of excipient, 1-1.5 parts of stabilizer, 9170-9590 parts of water for injection.
8. freeze dried powder according to claim 7, which is characterized in that the excipient is in mannitol, gelatin or sucrose One kind or its combination;The stabilizer is one kind or its combination in glutathione, serine or sucrose.
9. a kind of preparation method of freeze dried powder, which is characterized in that include the following steps:By membrane glycoprotein, excipient, stabilizer Be dissolved in water for injection, mix, filter, packing, precooling, vacuum drying to get.
10. the preparation method of a kind of freeze dried powder according to claim 9, which is characterized in that the precooling is included such as Lower step:4 DEG C are cooled to, refrigerates 1h-2h, is cooled to 0 DEG C~-10 DEG C, freezes 2h~3h;It is cooled to -25 DEG C~-30 DEG C, it is cold Freeze 1h~3h;- 45 DEG C~-55 DEG C are cooled to, freezes 2h~4h.
CN201711459727.6A 2017-12-28 2017-12-28 The applications of CD61 in treatment medication for treating pyemia is prepared and combinations thereof Pending CN108042792A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107998376A (en) * 2017-12-28 2018-05-08 南京东诺医药科技开发有限责任公司 The applications of CD42b in treatment medication for treating pyemia is prepared and combinations thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101020048A (en) * 2007-02-12 2007-08-22 广东天普生化医药股份有限公司 Pyemia treating medicine composition
CN102813925A (en) * 2012-07-30 2012-12-12 江苏大学附属医院 Application of carbon monoxide releasing molecules in preparing medicines for inhibiting blood coagulation activation diseases
CN107998376A (en) * 2017-12-28 2018-05-08 南京东诺医药科技开发有限责任公司 The applications of CD42b in treatment medication for treating pyemia is prepared and combinations thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101020048A (en) * 2007-02-12 2007-08-22 广东天普生化医药股份有限公司 Pyemia treating medicine composition
CN102813925A (en) * 2012-07-30 2012-12-12 江苏大学附属医院 Application of carbon monoxide releasing molecules in preparing medicines for inhibiting blood coagulation activation diseases
CN107998376A (en) * 2017-12-28 2018-05-08 南京东诺医药科技开发有限责任公司 The applications of CD42b in treatment medication for treating pyemia is prepared and combinations thereof

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孙运秀等人: "血小板膜糖蛋白CD61、CD62P在小鼠脓毒症炎性反应中的调控作用", 《中华实验外科杂志》 *
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107998376A (en) * 2017-12-28 2018-05-08 南京东诺医药科技开发有限责任公司 The applications of CD42b in treatment medication for treating pyemia is prepared and combinations thereof

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Application publication date: 20180518