CN105726520B - Lactone dimethylamine liposome atomized inhalation and its application with a smile - Google Patents
Lactone dimethylamine liposome atomized inhalation and its application with a smile Download PDFInfo
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- CN105726520B CN105726520B CN201610072594.6A CN201610072594A CN105726520B CN 105726520 B CN105726520 B CN 105726520B CN 201610072594 A CN201610072594 A CN 201610072594A CN 105726520 B CN105726520 B CN 105726520B
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- smile
- liposome
- lactone dimethylamine
- dimethylamine
- lactone
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- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
Abstract
The invention provides a kind of lactone dimethylamine liposome with a smile, and the liposome is to have a smile on one's face lactone dimethylamine and its derivative comprising effective ingredient using class surface reactive material as carrier.The lactone dimethylamine liposome with a smile is in the application in treatment pulmonary fibrosis in drug.Compared with the existing technology; it is provided by the invention to have a smile on one's face lactone dimethylamine atomized inhalation and its application in treatment pulmonary fibrosis medicine using PSMC as carrier; it is the moist protective effect by PSMC phospholipid bilayer structure identical with cell membrane and phosphatide; improve the Percentage bound of drug and alveolar cell; change pharmacokinetic characteristics; extend drug body in action time, significantly improve with a smile lactone dimethylamine to the therapeutic effect of pulmonary fibrosis.
Description
Technical field
The present invention relates to pharmaceutics fields, in particular to class pulmonary surfactant (plumonary
Surfactant mimic carrier, PSMC) it is being treated for lactone dimethylamine (ACT001) atomized inhalation with a smile of carrier
Application in pulmonary fibrosis.
Background technique
Neulized inhalation is the common of respiratory disease, such as asthma, pulmonary emphysema, bronchiectasis and chronic bronchitis etc.
Therapeutic modality.It is primarily due to: 1. huge (the about 140m of pulmonary absorption area2), and alveolar and the close phase of systemic circulation system
Even；2. epithelial barrier is thin, membrane permeability is high；3. inhalation administration has bioequivalence, good biocompatibility with intra arterial injection；
4. avoiding the first pass effect of liver and the influence to renal function.Atomized inhalation is applied to lung as a kind of inhalant
Disease is entered by respiratory nasal, can be used whenever and wherever possible for anyone, it is particularly possible to difficult towards children or diet
Old man and patient use, convenient and efficient, have a wide range of application.
Pulmonary fibrosis is clinically high-incidence pulmonary disease at present, and clinical manifestation is expiratory dyspnea, at fibre in lung interval
The hyperplasia of cell is tieed up, the deposition of extracellular matrix is excessive.Since pulmonary fibrosis is as caused by the injury of lungs of duration one
Pulmonary fibrosis occurs for denier, then is difficult to cure.There is no specific medicaments at present for the treatment of pulmonary fibrosis.Pulmonary fibrosis disease lethality
High, clinical treatment measure scarcity, therefore novel treatment pulmonary fibrosis is developed on the basis of understanding its pathogenesis in depth
Drug is extremely urgent.
Lactone dimethyl amine is the derivative of lactone with a smile with a smile, be by natural extract parithenolide be waste
, it is referred to as ACT001 herein.Research shows that ACT001 can by inhibit tumor necrosis factor (TNF-α),
The expression of interleukin-1 etc. and have anti-inflammatory effect.ACT001 can also be by adjusting pyruvate kinase in glycometabolism approach
(PKM2) conformation inhibits alveolar epithelial cells that differentiation, inhibition of the epithelium mesenchyma transformation (EMT) to myofibroblast occurs
The over-deposit of progressive inflammatory reaction, cellular damage and extracellular matrix in interstitial lung in lung tissue, to play
The effect for treating pulmonary fibrosis.
In order to play ACT001 to the greatest extent to the therapeutic effect of pulmonary fibrosis, this research provides a kind of novel
ACT001-PSMC atomized inhalation can significantly improve ACT001 to the therapeutic effect of pulmonary fibrosis.
Summary of the invention
In view of this, the purpose of the present invention is to provide a kind of using PSMC as the lactone dimethylamine liposome with a smile of carrier
Atomized inhalation (ACT001) and its application in pulmonary fibrosis therapeutic agent.
In order to achieve the above objectives, the technical solution of the invention is achieved in that
One kind having a smile on one's face lactone dimethylamine liposome, and the liposome includes drug using class surface reactive material as carrier
Effective component is to have a smile on one's face lactone dimethylamine and its derivative.
Further, the effective ingredient includes to have a smile on one's face lactone dimethylamine and its pharmaceutically acceptable salt hydrate
Or their combination.
Further, the class surface reactive material be class pulmonary surfactant, the class pulmonary surfactant by
Phosphatide and cholesterol composition.
Further, the phosphatide include lecithin, dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine,
Distearoyl Phosphatidylcholine or their combination.
Further, in the liposome carrier and effective ingredient weight ratio are as follows: carrier: effective ingredient=
5:1。
It further, also include the pharmaceutically acceptable auxiliaries of appropriate amount in the liposome.
The present invention also provides the preparation methods of the lactone dimethylamine liposome with a smile described in one kind, and step includes: first
Phosphatide and cholesterol are dissolved in ethyl alcohol according to a certain percentage, in being evaporated under reduced pressure on Rotary Evaporators, solvent is evaporated in uniform thin
Film；Then weighed lactone dimethylamine with a smile is dissolved in PBS buffer solution and is preheated；Solution after preheating is added to the film spun
In, aquation washes film, Probe Ultrasonic Searching, and filtering with microporous membrane must have a smile on one's face lactone dimethylamine liposome turbid liquor.
It is another object of the present invention to protect the lactone dimethylamine liposome with a smile drug in treatment pulmonary fibrosis
In application.
Further, the drug effect of the lactone dimethylamine liposome with a smile is by class pulmonary surfactant and cell membrane
The moist protective effect of identical phospholipid bilayer structure and phosphatide improves the Percentage bound of drug and alveolar cell, extends
Action time is realized in drug body.
Further, the administration mode of the liposome is nebulizer administration.
Compared with the existing technology, lactone dimethylamine liposome and its application are had a smile on one's face described in the invention with following excellent
Gesture:
It is provided by the invention using PSMC is the lactone dimethylamine atomized inhalation with a smile of carrier and it is fine in treatment lung
The application in chemical drug object is tieed up, is made by the moist protection of PSMC phospholipid bilayer structure identical with cell membrane and phosphatide
With the Percentage bound of raising drug and alveolar cell changes pharmacokinetic characteristics, extends action time in drug body, significantly mentions
Height has a smile on one's face lactone dimethylamine to the therapeutic effect of pulmonary fibrosis.
Detailed description of the invention
The attached drawing for constituting a part of the invention is used to provide to further understand the invention, present invention wound
The illustrative embodiments and their description made are used to explain the present invention creation, do not constitute the improper restriction to the invention.?
In attached drawing:
Fig. 1, the situation of change of each group mouse weight after administration is shown；
Fig. 2, influence of the Alevaire to pulmonary fibrosis model paragonimus cyst is shown；
Fig. 3, show administration after third week mouse tissue dicing effect figure.
Specific embodiment
Unless otherwise stated, term used herein all has the meaning that those skilled in the art routinely understand, in order to
It is easy to understand the present invention, some terms used herein have been subjected to following definitions.
It using in the specification and in the claims, singular type "one" and " this " they include plural reference, unless on
Hereafter separately there is clear statement.For example, term " (one) cell " includes the cell of plural number, including its mixture.
All number marks, such as pH, temperature, time, concentration, including range, are all approximations.It is to be understood that although
Term " about " is all added before always not describing all number marks explicitly.While it will also be understood that, although always not clear
Narration, reagent described herein is only example, and equivalent is known in the art.
Below with reference to examples and drawings come the present invention will be described in detail create.
The test material and its source that the present invention uses include:
(1) major experimental reagent
Egg yolk lecithin: white or pale yellow powder shape object or block, Shanghai Taiwei Pharmaceutical Co., Ltd., lot number
20110026.
Cholesterol: white powder, Shanghai Advanced viecle Technology Co., Ltd., product batch number B40333.
Ethyl alcohol: colourless irritant odor liquids are purchased from Tianjin chemical reagent supply and marketing company.
ACT001 fumarate: white powder is purchased from Tianjin Shang Deyao edge Science and Technology Co., Ltd., lot number
20131112.
Bleomycin Sulphate: white powder, Dalian U.S. logical sequence Technology Co., Ltd., No. CAS: 9041-93-4, article No.
MB1039, lot number: M0401A, purity: 91%.
(2) instrument consumptive material
Biohazard Safety Equipment: Thailand, Spain thing reaches (Telstar), model: Bio II A.
CO2Incubator: Shi Doukai instrument and equipment (Shanghai) Co., Ltd., model: STIK IL-161HI.
Inverted phase contrast microscope: producer: Olympus, model: CKX41.
Rotary Evaporators: model SHZ-111 knows purchased from Shanghai and reliable tests technical device Co., Ltd.
Fully-automatic dewatering machine: Leca company, model: ASP200S are purchased from
Paraffin wax embedding: Leca company, model: 1150C are purchased from
Slicer: Leca company, model: RM2245 are purchased from
Full-automatic tissue staining machine: Leca company, model: AUT0S TINER XL are purchased from
Full-automatic tissue mounting machine: Leca company, model: CV5030 are purchased from
Just set fluorescence microscope: purchased from Olympus, model: BX53
(3) mouse
Kunming mice (male): tonneau is tieed up by Academy of Military Medicine, PLA's experimental animal center and Beijing
Magnificent experimental animal Technology Co., Ltd. provides.After animal reaches, animal is received by special messenger and is raised in double corridor barrier environment mouse
Interior is filled in " experimental animal reception record sheet " (BG-017-V00), and when reception observes animal general condition, and random
It extracts animal to weigh, it is ensured that experimental animal and introduction standard are coincide substantially.Experimental animal uses credit number: SYXK (saliva)
2012-0003。
(4) cell line: NIH-3T3 cell, normal mouse fibroblast are limited purchased from Nanjing Keygen Biotech's development in science and technology
Company.
(5) preparation method of drug and reagent used in
A) NaCl 8g, KCl 0.2g, Na the preparation of PBS buffer solution (phosphate buffer): are weighed2HPO41.54g、
KH2PO40.2g is dissolved in ddH2In 0, PH to 7.4 is adjusted, 1L is settled to.It is used after needing 121 DEG C of high-temperature sterilizations.
B) preparation of ACT001 solution: ACT001 powder 1g is weighed, is dissolved in the PBS buffer solution of 100mL, is configured to
10mg/mL solution, after completely dissolution to it, with being used after 0.22 μm of filter filtration sterilization, matching while using when using every time.Solution
Preparation and use should all be operated in aseptic biosafety cabinet.
C) preparation of bleomycin solution: weighing 0.0100g Bleomycin Sulphate, is dissolved in 10mL physiological saline, prepares
At the solution of 1mg/mL, with 0.22 μm of membrane filtration, the preparation and filtering of solution should all operate in aseptic biosafety cabinet,
Matching while using.
D) configuration of formalin fixer: the PBS buffer solution of the formaldehyde of 100mL and 900mL are mixed.
The preparation of embodiment 1PSMC
Experimental method and step: egg yolk lecithin and cholesterol are dissolved in ethyl alcohol with the ratio of 5:1, in Rotary Evaporators
Upper 50 DEG C of reduction vaporization, solvent are evaporated in uniform film.Weighed ACT001 is dissolved in PBS and is preheated to 60 DEG C, addition is spun
Film in, aquation washes film, Probe Ultrasonic Searching, and filtering with microporous membrane obtains the ACT001 suspension of PSMC.
The foundation of 2 mouse pulmonary fibrosis model of embodiment and the detection of ACT001 pharmacodynamics
Experimental method and step:
1, the foundation of mouse pulmonary fibrosis model: 25 mouse are randomly divided into five groups, blank group, model group (lung fiber
Change model group), blank PSMC group (after modeling give blank PSMC), ACT001-PBS group (to drug containing PBS solution after modeling),
ACT001-PSMC group (gives drug containing PSMC) after modeling, and every group 5.The physiological saline of blank group every disposable stomach-filling 0.15mL
Solution；The other groups every disposable bleomycin solution for filling lung 0.15mL.
2, the drug treatment of pulmonary fibrosis mice: the second week after modeling gives mouse drug therapy, blank group and model
Group fills lung (simulating clinical nebulizer administration form) with the PBS of 0.1mL every time, and blank PSMC group uses the blank of 0.1mL every time
PSMC solution fills lung, and ACT001-PBS group fills lung with the PBS solution dissolved with ACT001 of 0.1mL every time, and ACT001-PSMC group is every
The secondary drug containing PSMC with 0.1mL fills lung.Administration 21 days.
3, the pathological examination of mouse pulmonary fibrosis: third week upon administration, dislocation are put to death, its lung tissue is taken, and weigh mouse
Lung weight is subsequently placed in formalin and fixes two days, rinses the fixer on lung tissue surface after fixed with flowing water, de- with pathological tissue
Water dispenser is carried out dehydrating lung tissue, through paraffin embedding, is sliced to investing tissue, HE dyeing, after mounting, sees under the microscope
It examines the variation of lung tissue and carries out histopathological scores, evaluate lung fibrosis degree by Szapiel method.
Standards of grading are as follows: 0 grade, no pulmonary interstitial fibrosis；1 grade, slight pulmonary interstitial fibrosis, extent of disease is confined to entirely
Below lung 20%；2 grades, moderate pulmonary interstitial fibrosis, extent of disease accounts for the 20%~50% of full lung, alveolar structure disorder；3 grades,
Severe pulmonary interstitial fibrosis, extent of disease is greater than 50%, fusion of pulmonary alveoli, pulmonary parenchyma structure disturbance.
4. statistical procedures
All data carry out ANOVA variance analysis through SPSS17.0 statistical software, are that difference has statistics with P < 0.05
Meaning.
Experimental result and evaluation
1. the weight of animals situation of change
The changes of weight situation of mouse is as shown in Figure 1 during administration: model group mouse body weight, which increasess slowly, shows lung fiber
Change model modeling success；It is more obvious than administration ACT001-PBS group body weight increase that ACT001-PSMC group is administered, shows ACT001PSMC
Good drug efficacy of the drug effect of Alevaire dosage form than drug is used alone, improves the availability of drug；To sky compared with model group
The mouse weight of PSMC group also increased, and illustrate that the lecithin in PSMC plays the role of moistening protection alveolar cell film,
It has some improvement to pulmonary fibrosis.
2. paragonimus cyst situation
By data and Fig. 2 paragonimus cyst variation diagram of 1 paragonimus cyst of table as it can be seen that the paragonimus cyst of model group is significantly higher than blank group,
The paragonimus cyst of PSMC group and the paragonimus cyst of blank group is administered without significant difference.Compared with model group, ACT001-PSMC Neulized inhalation
The paragonimus cyst of group significantly reduces, and effect is better than independent ACT001 inhalation group.Above data shows PSMC Alevaire dosage form
The availability that drug can be improved enhances the drug effect of drug.
Influence of 1 drug of table to mouse paragonimus cyst
Note: compared to the blank group, # indicates that P < 0.05, ## indicate P < 0.01；Compared with model group, * indicates P < 0.05, * *
Indicate P < 0.01.
3. mouse tissue dicing effect
Lung tissue section's result of administration mouse after three weeks as shown in figure 3, as seen from the figure, administration group compared with model group,
The pulmonary fibrosis degree of administration group is obviously improved, and the lung fibrosis level of mouse is substantially reduced, and what interstitial lung hyperplasia thickened shows
As improving.Pathological tissue appraisal result is as shown in table 2: the drug effect of ACT001PSMC Alevaire dosage form is than being used alone ACT001 mist
The good drug efficacy of change.
Influence of the table 2ACT001 to pulmonary fibrosis model histopathological scores
Note: compared to the blank group, # indicates that P < 0.05, ## indicate P < 0.01；Compared with model group, * indicates P < 0.05, * *
Indicate P < 0.01
Above embodiments show: ACT001-PSMC Alevaire targeting is in lung and ACT001 aqueous solution is used alone
Compared to the Percentage bound for increasing drug and alveolar cell, pharmacokinetic characteristics are changed, action time in drug body is extended, from
And improve its bioavilability.
The foregoing is merely the preferred embodiments of the invention, are not intended to limit the invention creation, all at this
Within the spirit and principle of innovation and creation, any modification, equivalent replacement, improvement and so on should be included in the invention
Protection scope within.
Claims (7)
1. a kind of lactone dimethylamine liposome with a smile for nebulizer administration, it is characterised in that: the liposome is with class lung
Surface reactive material is lactone dimethylamine or the hydration of its pharmaceutically acceptable salt with a smile comprising effective ingredient as carrier
Object or their combination；The weight ratio of carrier and effective ingredient in the liposome are as follows: carrier: effective ingredient=5:
1。
2. a kind of lactone dimethylamine liposome, feature with a smile for nebulizer administration according to claim 1 exists
In: the class pulmonary surfactant is made of phosphatide and cholesterol.
3. a kind of lactone dimethylamine liposome, feature with a smile for nebulizer administration according to claim 2 exists
In: the phosphatide includes lecithin, dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, distearoylphosphatidyl
Choline or their combination.
4. a kind of lactone dimethylamine liposome with a smile for nebulizer administration described in claim 1, it is characterised in that: institute
It states in liposome also comprising the pharmaceutically acceptable auxiliaries of appropriate amount.
5. a kind of preparation side of lactone dimethylamine liposome with a smile for nebulizer administration according to claim 2
Method, it is characterised in that: phosphatide and cholesterol are dissolved in ethyl alcohol according to a certain percentage first, steamed in being depressurized on Rotary Evaporators
Hair, solvent are evaporated in uniform film；Then weighed lactone dimethylamine with a smile is dissolved in PBS buffer solution and is preheated；After preheating
Solution be added in the film that spins, aquation washes film, Probe Ultrasonic Searching, and it is mixed that filtering with microporous membrane must have a smile on one's face lactone dimethylamine liposome
Suspension.
6. a kind of purposes of the lactone dimethylamine liposome with a smile for nebulizer administration, special described in claim 1 or 3
Sign is: the liposome is the application in preparation treatment pulmonary fibrosis in drug.
7. a kind of purposes of lactone dimethylamine liposome with a smile for nebulizer administration according to claim 6,
Be characterized in that: the drug effect of the lactone dimethylamine liposome with a smile is by class pulmonary surfactant phosphorus identical with cell membrane
The moist protective effect of lipid bilayer structure and phosphatide improves the Percentage bound of drug and alveolar cell, extends in drug body
What action time was realized.
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| CN109381425A (en) * | 2017-08-08 | 2019-02-26 | 于晓彤 | A kind of preparation method of atomized inhalation |
| CN110856716B (en) * | 2018-08-22 | 2023-05-23 | 天津尚德药缘科技股份有限公司 | Application of compound and pharmaceutical composition thereof in preventing and treating kidney fibrosis |
| CN111434336B (en) * | 2019-01-11 | 2022-10-04 | 天津尚德药缘科技股份有限公司 | Application of compound and pharmaceutical composition thereof in prevention and treatment of peritoneal fibrosis |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011131103A1 (en) * | 2010-04-23 | 2011-10-27 | 天津尚德药缘科技有限公司 | Sphaelactone derivatives, their pharmaceutical compositions, preparation methods and uses |
| CN102579426A (en) * | 2011-01-12 | 2012-07-18 | 韩颖 | Application of parthenolide as platelet-activating factor (PAF) antagonist |
| CN103622954A (en) * | 2012-08-22 | 2014-03-12 | 龙海波 | Applications of sesquiterpene lactone compound and derivative of sesquiterpene lactone compound in treatment of diabetes |
| CN104876899A (en) * | 2014-02-28 | 2015-09-02 | 天津尚德药缘科技股份有限公司 | Dimethylamino sphaelactone fumarate and use thereof |
-
2016
- 2016-02-02 CN CN201610072594.6A patent/CN105726520B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011131103A1 (en) * | 2010-04-23 | 2011-10-27 | 天津尚德药缘科技有限公司 | Sphaelactone derivatives, their pharmaceutical compositions, preparation methods and uses |
| CN102579426A (en) * | 2011-01-12 | 2012-07-18 | 韩颖 | Application of parthenolide as platelet-activating factor (PAF) antagonist |
| CN103622954A (en) * | 2012-08-22 | 2014-03-12 | 龙海波 | Applications of sesquiterpene lactone compound and derivative of sesquiterpene lactone compound in treatment of diabetes |
| CN104876899A (en) * | 2014-02-28 | 2015-09-02 | 天津尚德药缘科技股份有限公司 | Dimethylamino sphaelactone fumarate and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| 肺吸入给药剂型的研究进展;蹇小婷等;《西北药学杂志》;20050825;第20卷(第04期);第185-186页 |
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