CN108066348A - Application of the ponticin in anti-fibrosis drug is prepared - Google Patents
Application of the ponticin in anti-fibrosis drug is prepared Download PDFInfo
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- CN108066348A CN108066348A CN201611007654.2A CN201611007654A CN108066348A CN 108066348 A CN108066348 A CN 108066348A CN 201611007654 A CN201611007654 A CN 201611007654A CN 108066348 A CN108066348 A CN 108066348A
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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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
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Abstract
The present invention relates to the medical new application of ponticin, i.e. application of the ponticin in anti-fibrosis drug is treated.The experimental results showed that, ponticin can improve the pulmonary fibrosis degree of BLM inductions in animal body, reduce HYP levels in model mice body, and display ponticin can be used for treating pulmonary fibrosis disease.Raw material sources of the present invention are extensive, at low cost, toxic side effect is small, are with a wide range of applications.
Description
Technical field
The invention belongs to Chemistry for Chinese Traditional Medicine field, more particularly to application of the ponticin in pulmonary fibrosis medicine is treated.
Background technology
Pulmonary fibrosis (Pulmonary fibrosis, PF) is a kind of the excessively heavy with extracellular collagen of progress sexual development
The interstitial lung disease that product is characterized, the disease death rate is high, once it makes a definite diagnosis, it is generally only 3 ~ 5 years existence time limit of patient, clinical
On there is no effective therapy.Recent study finds that virus infection is smoked, and reflux esophagitis is long-term exposed to wood
Bits, the factors such as metallic dust working environment and age can cause intrapulmonary epithelial cell to be damaged, and pass through a series of approach
Start the abnormal repair process of tissue, ultimately result in the generation of fibrosis.The pathogenesis of pulmonary fibrosis is not yet completely clear and definite, mesh
Preceding research thinks that common pathological change is alveolar epithelial cells damage, fibroblast proliferation and a large amount of collagen depositions.
The incidence of pulmonary fibrosis is in rising trend in the whole world, although at present there are many drug in clinical test, without strong
Any drug of evidence display can be obviously improved the state of an illness of fibrosis patient.Traditional medicine still with glucocorticoid and
Based on immunosuppressor/cell toxicity medicament, such as cortin, imuran or cyclophosphamide, but these drugs are without remarkable result,
And side effect is big.The limitation treated at present forces researcher and clinician to constantly look for effective anti-fibrosis medicine
Object.
Internal collagenic supersession is unbalance for one of important pathological characteristic of pulmonary fibrosis.The collagen component of intrapulmonary mainly has I,
IIIth, IV and V-type, I, III Collagen Type VI commonly uses the index for doing reflection pulmonary fibrosis, and type Ⅳ collagen is the main component of basilar memebrane, V type
Collagen is one of intrapulmonary collagen component.During pulmonary fibrosis, type Ⅳ collagen is first subjected to damage, substrate film integrality by
It destroys, then centered on V Collagen Type VI, based on Type I collagen, supplemented by III Collagen Type VI, the pattern of a little type Ⅳ collagen intervention, greatly
The extrtacellular matrix depositions such as the collagen of amount enable pulmonary fibrosis process to start and carry out sexual development.
Pulmonary fibrosis is an injury of lungs and repairs unbalance process.At the position of damage, fibroblast proliferation differentiation
For myofibroblast, myofibroblast is the main cell for secreting collagen, can jointly be joined with other cells and cell factor
With the reparation after damage.The disappearance of myofibroblast physiological is the key that terminate this repair process.As flesh into fiber finer
The index of born of the same parents if the expression of α-SMA albumen maintains the high level of comparison, illustrates the lasting presence of myofibroblast.After if
Continuous α-SMA expression continuously decreases, then explanation myofibroblast in repair process fades away, and disease improves.Most lungs are fine
It is observed that inflammation and fibrosis and depositing in the tissue of dimensionization patient, prompting inflammatory reaction takes part in the formation of pulmonary fibrosis,
Therefore the effect of the cell factors in pulmonary fibrosis such as TGF-β becomes the hot spot studied at present.TGF-β1It is considered as the most
Crucial fibrogenic factor, works in multiple links of pulmonary fibrosis occurrence and development.
Ponticin (Rhapontin) is diphenyl ethylene derivatives, is in a kind of be widely present in polygonaceae plant leaf
Medicine active ingredient has the effects that reducing blood lipid, hypoglycemic, anti-inflammatory, antitumor, anticancer, antibacterial and anti-oxidant.
At present, the related patents in relation to ponticin have nearly more than 15 piece：It is concentrated mainly on extracting and developing, preparation, Yi Ji
Treat the application of ulcerative colitis, osteoporosis, neuropathy, whitening etc..The improvement of there is not been reported ponticin
Pulmonary fibrosis acts on and its purposes in this disease medicament is treated.
The content of the invention
It is an object of the invention to which the prior art is overcome to limit to, provide it is a kind of it is curative for effect, toxic side effect is smaller, at low cost
The drug of honest and clean treatment pulmonary fibrosis.More particularly to one kind with ponticin drug as main component and its treatment or/
With the application in prevention pulmonary fibrosis disease.
The present invention discloses the medical new application of ponticin first, i.e., in treating or/and preventing pulmonary fibrosis medicine
Application.
The present invention also provides a kind of pharmaceutical compositions treated or/and prevent pulmonary fibrosis, and specifically it is by effective agent
The ponticin of amount is active ingredient, in addition to learn the medicament that acceptable auxiliary material or complementary ingredient are prepared.
Further, mass percent of the ponticin in the medicament is 5-65%.
Further, mass percent of the ponticin in the medicament is 15-35%.
The pharmaceutically acceptable carrier is various pharmaceutically common auxiliary materials and/or excipient, including (but unlimited
In) carbohydrate（Such as lactose, dextrose and saccharose）, starch（Such as cornstarch and potato starch）, cellulose and its derivates（Such as
Sodium carboxymethylcellulose, ethyl cellulose and methylcellulose）, tragacanth gum powder, malt, gelatin, talcum, kollag
（Such as stearic acid and magnesium stearate）, calcium sulfate, vegetable oil, such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and cocoa
Oil, polyalcohol（Such as propylene glycol, glycerine, D-sorbite, mannitol and polyethylene glycol）, alginic acid, emulsifier（Such as Tween）,
Wetting agent（Such as NaLS）, colorant, flavoring agent, tablet agent, stabilizer, antioxidant, preservative, apirogen water,
Isotonic salting liquid and phosphate buffer etc.；The carrier can improve the stability, activity and biological effectiveness of formula as needed
Deng or in the case of oral generate acceptable mouthfeel or smell.
Any conventional form can be made in the pharmaceutical preparation of the present invention according to the universal method in pharmacy, including oral
Preparation and ejection preparation.The oral formulations are preferably tablet, granule, pill, pulvis, syrup, decoction and capsule；
More preferably tablet, granule, pill and capsule.
Ponticin used in pharmaceutical preparation of the present invention may be employed the prior art and be carried from Miao Ke rheum officinale platymisciums
Separation is taken, it can also be directly from being bought on the market.Further, the ponticin can use its pharmaceutically acceptable
Derivative or salt replace.
The present inventor has found that ponticin can improve the pulmonary fibrosis degree of BLM inductions by lot of experiments, reduces
HYP is horizontal in model mice body, and display ponticin can be used for the novel medical use for the treatment of pulmonary fibrosis disease.In short, soil is big
Xanthosine shows the activity of stronger pulmonary fibrosis resistant, possesses potentiality and prospect of the exploitation into corresponding clinical medicine.In addition, this hair
Bright experiment material derives from plant, and former plant distributions scope is wide, at low cost, is with a wide range of applications.
Obviously, the above according to the present invention according to the ordinary technical knowledge and customary means of this field, is not departing from
On the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples does further specifically the above of the present invention again
It is bright.But the scope that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to following embodiment.It is all to be based on the above of the present invention
The technology realized all belongs to the scope of protection of the present invention.
Description of the drawings
The influence that Fig. 1 ponticins change the mouse weight during modeling 28 days.
Influence of Fig. 2 ponticins to the mouse paragonimus cyst of modeling the 14th, 28 day.###p <0.001, versus control
Group；***p <0.001, versus model group；Positive control medicine：Prednisone acetate.
Influence (HE dyeing × 200) of Fig. 3 ponticins to lung tissue degree of inflammation.Positive control medicine：Acetic acid sprinkles Buddhist nun
Pine.
Influence (Massson dyeing × 200) of Fig. 4 ponticins to lung fibrosis degree.Positive control medicine：
Prednisone acetate.
Influence of Fig. 5 ponticins to HYP contents in the mouse lung tissue of modeling the 14th, 28 day.###p < 0.001,
Versus control groups；***p <0.001, versus model group；Positive control medicine：Prednisone acetate.
Specific embodiment
1 ponticin of embodiment improves the mouse pulmonary fibrosis of bleomycin induced.
1 material and instrument
ICR mouse, male, weight 18-22 g are provided by Yangzhou comparative medicine center.Wahaha Pure Water.Prednisone acetate,
Zhejiang Province XianJu Pharmacy stock Co., Ltd.Chloraldurate, Sinopharm Chemical Reagent Co., Ltd..Hydroxyproline kit, south
Bioengineering Research Institute is built up in capital.
2 experimental methods
ICR male mices are divided into blank group, model group, positive drug group, ponticin high dose group, ponticin low dose group,
Every group each 10.Mouse peritoneal injects 10 ml/kg, 4% chloraldurate is anaesthetized, after mouse anesthesia, fixed mouse, and disinfection
Mouse neck.Mouse skin of neck is longitudinally cut off with scissors, fascia and muscle, exposure tracheae are torn with tweezers longitudinal direction passivity.Note
Emitter is pierced into tracheae, blank group saline injection, remaining each group injects bleomycin (5 mg/kg).Then rapidly by mouse
Plate is upright, rotates mouse plate, observes mouse breathing situation, sterilizes neck wound with 75% alcohol swab after rotation, sews up a wound, and
Suture drips 1-2 drop penicillin injection liquids.The mouse cage that postoperative mouse is put back to dried and clean is rested, and waits revival, about l-2 h
After revive, normal raising afterwards.
Start within the 7th day after modeling, the daily gavage physiological saline of blank group, model group, 6.67 mg/kg/ of positive drug group gavage
D prednisone acetates, ponticin high dose group gavage 50 mg/kg/d, 100 mg/kg/d of ponticin low dose group gavage.Even
Continuous gavage was to the 28th day.Mouse, record of weighing were put to death respectively at the 14th, 28 day, lung tissue, the washing of ice physiology salt are taken out in dissection
Only, weigh after blotting paper blots, calculate paragonimus cyst, paragonimus cyst=lung weight (mg)/weight (g).Left small lung is put into 4% neutral formalin
Middle fixation, dehydration of alcohol step by step, dimethylbenzene is transparent, waxdip, and after paraffin embedding, lung is observed in conventional section, HE, Masson dyeing
Tissue morphology, injury of lungs and pulmonary fibrosis degree.Other lobe of the lung leaflets preserve, for the measure of HYP contents.
All data are represented with mean ± standard deviation (X ± SD).It is handled using 11.5 statistical softwares of SPSS, statistics is adopted
With one-way analysis of variance (one-way ANOVA), P<0.05 represents that difference is statistically significant.
Influence of 3 ponticins to model mice weight
Compared with Normal group, model group mouse weight is decreased obviously；Compared with model group mouse weight, ponticin
High and low dose group and positive drug（Prednisone acetate）The weight of group has apparent rising.Ponticin is prompted 50,100
The constitution of bleomycin induced pulmonary fibrosis mice can be improved under mg/kg dosage, slowed down under pulmonary fibrosis model mouse weight
Drop degree（Fig. 1）.
Influence of 4 ponticins to model mice paragonimus cyst
Compared with Normal group, model group mouse paragonimus cyst substantially increases and difference is statistically significant（P<0.001）；With
Model group mouse paragonimus cyst compares, ponticin high and low dose group and positive drug（Prednisone acetate）The paragonimus cyst of group is equal
It is decreased obviously, there is significant difference（P<0.001）.Prompting ponticin can improve rich under 50,100 mg/kg dosage
The mouse pulmonary fibrosis of Lay mycin induction, slows down model mice pulmonary fibrosis development degree（Fig. 2）.
Influence of 5 ponticins to model mice lung tissue
Histopathologic slide dyes through HE, Masson, the results showed that the mouse lung tissue structural integrity of Normal group is clear, lung
Bubble interval does not thicken, and alveolar space is bright, and intracavitary has no apparent exudate, and alveolar space has no inflammatory cell infiltration, without into fiber finer
Born of the same parents' hyperplasia；Visible a small amount of collagenous fibres for dying blueness, are the main of extracellular matrix in the lung tissue of Normal group mouse
Component.Model group mouse alveolar structure destroys, and alveolar septum is broadening, and massive inflammatory cells infiltrated urgency fibroblast increases
Raw, a large amount of collagen depositions, pulmonary fibrosis is formed, after Masson dyeing visible volume densification be dyed to the collagenous fibres of blueness, be in
The characteristics of pencil or sheet deposit, substantially conform to pulmonary fibrosis, then illustrate that experiment mice pulmonary fibrosis model is successfully prepared.Through soil
After rheochrysin treatment, it is seen that mouse lung tissue structural integrity is clear, and alveolar septum slightly thickens, inflammatory cell infiltration and into fiber finer
Born of the same parents' hyperplasia degree is lighter than model group.After positive drug prednisone acetate is treated, positive controls mouse alveolar septum is wider,
Alveolar space narrows, more inflammatory cell infiltration and fibroblast proliferation, and lesion degree mitigates compared with model group.Ponticin is administered
Compared with model group, fibrosis mitigate for group and positive drug group（Fig. 3 and Fig. 4）.
Influence of 6 ponticins to HYP contents in model mice lung tissue
Hydroxyproline (HYP) is by a kind of amino acid of ctgf protein hydrolysis gained, accounts for the 14% of collagen weight, right
The stability of collagen plays a crucial role, due to collagen be uniquely containing protein more HYP, measure HYP content energy
Reflect the total amount variation of tissue collagen.The the 14th, the 28 day content that HYP in lung tissue is detected with digestion method after modeling.With it is right
It is compared according to group, model group lung tissue HYP contents dramatically increase at 14,28 days（P<0.001）, compared with model group, ponticin
Administration group can obviously reduce HYP contents in lung tissue（P<0.001）.Prompt eupatilin equal under 50,100 mg/kg dosage
The mouse pulmonary fibrosis of bleomycin induced can be improved, reduce model expression of collagen in lung fiber content, slow down model mice lung fibre
Dimensionization development degree（Fig. 5）.
7 discuss
Compared with model group, ponticin high and low dose group can be obviously improved weight, reduce lungs index, reduce lung tissue
Middle HYP contents, and pathological examination shows that ponticin administration group lung tissue structure makes moderate progress, alveolar structure is undermined alveolar
Septal thickening degree has mitigation, and inflammatory cell infiltration is reduced, and collagen contents are reduced.Compared with Normal group, model
HYP contents dramatically increase in group mouse lung tissue, and after drug is given, mouse fibrosis are also reduced to varying degrees,
HYP contents are remarkably decreased in lung tissue.Illustrate that ponticin plays a role during pulmonary fibrosis, and reduce in lung tissue
The expression of HYP.
In conclusion lung mechanics caused by ponticin can influence bleomycin damage, it is fine to mitigate lung tissue inflammation, lung
Dimensionization degree, and inhibit expression of collagen in lung secretion, ponticin has the new application for the treatment of pulmonary fibrosis disease.
Claims (6)
1. application of the ponticin in the drug for preparing prevention or/and treatment pulmonary fibrosis.
2. a kind of as described in claim 1, drug prevented or/and treat pulmonary fibrosis, it is characterised in that：It is by effective quantity
Ponticin for active ingredient, in addition the medicament that pharmaceutically acceptable auxiliary material and/or complementary ingredient are prepared.
3. drug as claimed in claim 2, it is characterised in that ponticin content is 5%-65% in the medicament；More preferably
Content is 15%-35%.
4. medicament as claimed in claim 2, it is characterised in that：The medicament is the pharmaceutical dosage form through gastrointestinal administration.
5. medicament as claimed in claim 3, it is characterised in that：The pharmaceutical dosage form through gastrointestinal administration be selected from granule,
Tablet, powder, oral liquid, pill, capsule.
6. the drug as described in claim 1,2, it is characterised in that：The ponticin can use ponticin pharmaceutically
Acceptable derivates or salt replace.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611007654.2A CN108066348A (en) | 2016-11-16 | 2016-11-16 | Application of the ponticin in anti-fibrosis drug is prepared |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611007654.2A CN108066348A (en) | 2016-11-16 | 2016-11-16 | Application of the ponticin in anti-fibrosis drug is prepared |
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| CN108066348A true CN108066348A (en) | 2018-05-25 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103055313A (en) * | 2005-07-07 | 2013-04-24 | 西特里斯药业公司 | Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders |
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- 2016-11-16 CN CN201611007654.2A patent/CN108066348A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103055313A (en) * | 2005-07-07 | 2013-04-24 | 西特里斯药业公司 | Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders |
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Application publication date: 20180525 |