CN108452291A - The method for treating ulcerative colitis with natural sericin - Google Patents

The method for treating ulcerative colitis with natural sericin Download PDF

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Publication number
CN108452291A
CN108452291A CN201810721564.2A CN201810721564A CN108452291A CN 108452291 A CN108452291 A CN 108452291A CN 201810721564 A CN201810721564 A CN 201810721564A CN 108452291 A CN108452291 A CN 108452291A
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sericin
ulcerative colitis
sodium alginate
natural
treating ulcerative
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肖波
马雅
陈久存
汪敏
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Southwest University
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Southwest University
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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
    • A61K38/1767Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • 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
    • A61K47/02Inorganic compounds
    • 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
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Inorganic Chemistry (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses natural sericins to treat ulcerative colitis(Ulcerative colitis,UC)Method.This method mainly prepares sericin by high temperature alkali dissolution method, by sericin/sodium alginate soln/CaCl2•2H2O solution mixing systems are standby at the silk gum treated for UC/sodium alginate composite hydrogel oral preparation, give intragastric administration on mice.Currently without using sericin not reported in terms of UC treatments, therefore the invention has convincingly demonstrated sericin has good application prospect in terms of UC oral medications.

Description

The method for treating ulcerative colitis with natural sericin
Technical field
The present invention relates to the fields such as pharmacy, pharmacology and Bio-Nano-Materials, and in particular to sericin treats ulcer The method of property colitis.
Background technology
Silk is secreted silk liquid concretionary continuous fiber when matured silkworm cocoons, is a natural fiber albumen.It is main To contain fibroin albumen and sericin.Compared with fibroin albumen, sericin has the amino acid composition of different and divides Son amount distribution, thus larger difference is showed in structure, form, mechanical property and biology performance etc..Compared to silk Fibroin, the mechanical performance of sericin is poor, degradation is very fast, thus in one section of very long period people to its attention degree Far below the fibroin of silk internal layer.In silk goods industry, silk gum is often taken as waste, is discharged with waste water, and then is led Cause it that effective development and utilization is not yet received.Since 2000, recover one's original simplicity, the back to nature green revolution is advocated, Silk has been to be concerned by more and more people and pursues.
The sericin for accounting for silk total amount 20 ~ 30%, by feat of its abundant functional group, it is good it is water-soluble, nontoxic, Good biocompatibility, promote the performances such as cell adhesion and proliferation activity, anti-oxidant and tyrosinase inhibitory action, gradually at For the research hotspot of natural new material and field of medicaments.Lei et al.(ACS Appl. Mater. Interfaces 2016, 8, 6577−6585)It is prepared for the multi-functional silk gum nano-particle of load adriamycin for having cancer target folacin coupled, especially It is applicable in and treats the cancer with high level expression folacin receptor by delivering hydrophobicity chemotherapeutics.Ayumu et al.(Int. J. Pharm.2011, 407,44-52)Silk gum is made biodegradable silk gum film, gel and sponge, albumen in controllable silk gum The sustained release of matter.Zhaorigetu et al.(Biosci. Biotechnol. Biochem. 2001, 65, 2181- 2186)It was found that sericin inhibits the mouse Colon that 1,2- dimethylhydrazines are handled swollen by reducing oxidative stress and cell Proliferation The generation of tumor.Aramwit et al.(Arch. Dermatol. Res.2013,305, 585-594.)Confirm that sericin can promote Into the healing of the open surface of a wound, but in clinical studies, the application of silk gum is restricted, and also proves that sericin is being burnt for the first time Hinder in Wound treating is safely and effectively.Thitikan et al.(Int. J. Biol. Macromol. 2015, 80, 636- 643)It is prepared for sodium alginate nanoparticles of load sericin, sodium alginate nanoparticles of the sericin load of preparation It is further configured to surface gel, gel preparation is stable, the sea of topical application sericin load under acceleration conditions Sodium alginate gel preparation can reach the inhibition of inflammation of carragheen induction.
Ulcerative colitis(Ulcerative colitis, UC)It is a kind of chronic recurrent idiopathic disease, feature It is that colonic epithelium barrier is impaired and inflammation stable state is destroyed.The incidence of UC increases increasingly in recent years, and it is intractable to have been cited as the world Disease.It is extremely difficult to cure UC completely at present, is still based on anti-inflammatory and adjusting immune response, so the purpose for the treatment of is slow Inflammation is solved, the recurrent exerbation of inflammation is inhibited and promotes Mucous rehabilitation.The existing drug for treating UC:Such as aminosalicylic acids Salazosulfadimidine and 5-aminosalicylic acid;Hydrocortisone, prednisone, the dexamethasone of glucocorticoids;Biological inhibition The imuran of agent class, ciclosporin A;Also gradually applied to UC non-steroidal anti-inflammatory drugs curcumins treated etc..These drugs because Its side effect is larger, expensive, water-soluble bad or bioavilability is low etc. limits its application.Current research mainly collects In finding in terms of preparation process is simple, good biocompatibility, bioavilability are high and cheap drug.
Sericin applies no relevant report, the present invention to provide sericin treatment UC's for the first time in terms of UC treatments Method contributes to us to carry out further research and exploitation to silk gum, there is prodigious economic and clinical conversion meaning.
Invention content
In consideration of it, treating UC using the sericin extracted from natural silk the purpose of the present invention is to provide a kind of Method, sericin show preferably treat UC effect.
Technical scheme of the present invention is specific as follows:
1. the method for treating ulcerative colitis with natural sericin, which is characterized in that include the following steps:
(1)Sericin is extracted with the method for high temperature alkaline degradation, after purification, freeze-drying obtains sericin;
(2)It will(1)Obtained sericin/sodium alginate soln/CaCl2•2H2Silk gum/the sea treated for UC is made in O solution Mosanom composite hydrogel;
(3)It will(2)Obtained silk gum/sodium alginate composite hydrogel suffers from the progress gavage processing of UC mouse to oral, for UC's Treatment.
Further, the step(1)The molecular weight of middle sericin is more than 1 KDa.
Preferably, the step(1)The molecular weight of middle sericin is the KDa of 1 KDa ~ 220.
Further, the step(2)The quality of the sericin and sodium alginate of middle silk gum/sodium alginate composite hydrogel Than being 1 ~ 50, ion crosslinking agent CaCl2•2H2A concentration of 1 ~ 5 wt% of O solution.
Preferably, by the step(2)The matter of the sericin and sodium alginate of middle silk gum/sodium alginate composite hydrogel Amount is than being 100:(10~50), ion crosslinking agent CaCl2•2H2A concentration of 1 ~ 2 wt% of O solution.
Further, the step(3)In Mouse oral sericin dosage be 0.1 ~ 5 g/kg.
Preferably, by the step(3)In Mouse oral sericin dosage be 0.5 g/kg.
Compared with the prior art, the advantage of the invention is that:
(1)The natural sericin utilized in the present invention is extracted from silk, and materials are simple and of low cost.
(2)The present invention is by by sericin/sodium alginate soln/CaCl2•2H2O solution is made answers for what UC was treated Heshui gel carries out gavage to mouse, achieves the effect of good treatment UC.
(3)The method that the present invention provides sericin treatment UC for the first time.For current sericin in terms of UC treatments Using the extensive concern for not causing scientific research personnel and pharmaceuticals, proposition of the invention can contribute to us and be carried out to silk gum Further research and exploitation have prodigious economic and clinical conversion meaning.
Description of the drawings
To make the objectives, technical solutions, and advantages of the present invention clearer, below in conjunction with attached drawing to the present invention make into The detailed description of one step, wherein:
Fig. 1, Fig. 2, Fig. 3 and Fig. 4 are natural sericin in the embodiment of the present invention 1 to the therapeutic effect figure of UC.
Specific implementation mode
Hereinafter reference will be made to the drawings, and the preferred embodiment of the present invention is described in detail, but is not limited to the present invention Range.
Embodiment 1
(1)Silk gum is extracted with the method for high temperature alkaline degradation, after purification, it is the KDa's of 1 KDa ~ 220 that freeze-drying, which obtains molecular weight, Sericin;
(2)It will(1)Obtained sericin/sodium alginate soln/CaCl2•2H2O solution mixing systems must be used for the silk of UC treatments The mass ratio of glue/sodium alginate composite hydrogel, wherein sericin and sodium alginate is 33:7, ion crosslinking agent CaCl2• 2H21.04 wt% of concentration of O;
(3)It will(2)Obtained silk gum/sodium alginate composite hydrogel is to taking orally administration group(Sericin oral dose:0.5 g/ Kg, sericin weight/mouse weight)Mouse carries out gavage processing, is used for the treatment of UC.
Experiment 1:Mouse is divided into 3 groups, respectively healthy group, dextran sulfate sodium salt(dextran sulfate sodium, DSS)Processing group, oral medication group(Sericin oral dose:0.5 g/kg, sericin weight/mouse weight), first The induction of mouse UC models is carried out, healthy group is drunk drinking water, and DSS processing group, oral medication group freely drink 3.5% DSS Solution.Composite hydrogel is made in natural sericin and sodium alginate.It is small to oral administration group daily since DSS processing Mouse carries out gavage processing, and health group and DSS processing groups use phosphate buffered saline solution daily(phosphate buffer saline, PBS)Gavage, as a contrast.When DSS processing group mouse weights decline 10% or so, according to healthy group, DSS processing group and oral The sequence of administration group dissects mouse, takes its colon, measures length, weighs;Its spleen is taken, is weighed, numerical value is recorded.
Shown in Fig. 1, ascendant trend is presented always in health group mouse weight, and DSS processing group mouse weight fall off rates are most fast, Weight of the mouse weight of oral medication group close to health group mouse;
Fig. 2 is separate groups of mice colon lengths figure, and the mouse Colon length of DSS processing groups obviously shortens, oral medication group it is small Colon lengths of the colon lengths of mouse close to health group mouse;
Fig. 3 is separate groups of mice colon weight figure, and the mouse Colon weight of DSS processing groups is substantially reduced, oral medication group it is small Colon weight of the colon weight of mouse close to health group mouse;
Fig. 4 is the spleen weight figure of separate groups of mice, and the mouse spleen weight of DSS processing groups significantly increases, oral medication group Spleen weight of the spleen weight of mouse close to health group mouse;In a word tomorrow, right sericin had well the treatment of UC Effect.
Finally illustrate, the above examples are only used to illustrate the technical scheme of the present invention and are not limiting, although passing through ginseng According to the preferred embodiment of the present invention, invention has been described, but it will be understood by those of ordinary skill in the art that, it can To make various changes to it in the form and details, without departing from of the invention defined by the appended claims Spirit and scope.

Claims (7)

1. the method for treating ulcerative colitis with natural sericin, which is characterized in that include the following steps:
(1)Sericin is extracted with the method for high temperature alkaline degradation, after purification, freeze-drying obtains sericin;
(2)It will(1)Obtained sericin/sodium alginate soln/CaCl2•2H2O solution mixing systems must be used for ulcerative colitis (Ulcerative colitis, UC)Silk gum/sodium alginate composite hydrogel for the treatment of;
(3)It will(2)Obtained silk gum/sodium alginate composite hydrogel carries out oral administration gavage processing to suffering from UC mouse, is used for the disease The treatment of disease.
2. the method according to claim 1 for treating ulcerative colitis with natural sericin, it is characterised in that:It is described Step(1)The molecular weight of middle sericin is more than 1 KDa.
3. the method according to claim 1 for treating ulcerative colitis with natural sericin, it is characterised in that:It is described Step(2)The mass ratio of sericin and sodium alginate in middle silk gum/sodium alginate composite hydrogel is 1 ~ 50, ionomer Agent CaCl2•2H2A concentration of 1 ~ 5 wt% of O solution.
4. the method according to claim 1 for treating ulcerative colitis with natural sericin, it is characterised in that:It is described Step(3)In the dosage for suffering from UC Mouse oral sericins be 0.1 ~ 5 g/kg.
5. the method according to claim 2 for treating ulcerative colitis with natural sericin, it is characterised in that:It is described Step(1)The molecular weight of middle sericin is 1 ~ 220 KDa.
6. the method according to claim 3 for treating ulcerative colitis with natural sericin, it is characterised in that:It is described Step(2)The sericin of middle silk gum/sodium alginate composite hydrogel and the mass ratio of sodium alginate are 100:(10~50), from Sub- crosslinking agent CaCl2•2H2A concentration of 1 ~ 2 wt% of O solution.
7. the method according to claim 4 for treating ulcerative colitis with natural sericin, it is characterised in that:It is described Step(3)In the dosage for suffering from UC Mouse oral sericins be 0.5 g/kg.
CN201810721564.2A 2018-07-04 2018-07-04 The method for treating ulcerative colitis with natural sericin Withdrawn CN108452291A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109258963A (en) * 2018-09-18 2019-01-25 浙江汇能生物股份有限公司 A kind of calcium polycarbophil stomach floating particle and the application on livestock and poultry

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CN103313716A (en) * 2010-11-30 2013-09-18 瑞瑟医药有限公司 Topical compositions for preserving or restoring the integrity of mucosae
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109258963A (en) * 2018-09-18 2019-01-25 浙江汇能生物股份有限公司 A kind of calcium polycarbophil stomach floating particle and the application on livestock and poultry

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