CN101797373A - Application of marine peptide in preparing medicament for promoting caesarean section postoperation recovery and health food - Google Patents
Application of marine peptide in preparing medicament for promoting caesarean section postoperation recovery and health food Download PDFInfo
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- CN101797373A CN101797373A CN200910008620A CN200910008620A CN101797373A CN 101797373 A CN101797373 A CN 101797373A CN 200910008620 A CN200910008620 A CN 200910008620A CN 200910008620 A CN200910008620 A CN 200910008620A CN 101797373 A CN101797373 A CN 101797373A
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Abstract
The invention relates to a marine peptide product and application thereof in preparing a medicament for promoting caesarean section postoperation recovery, a health food or food. The marine peptide is a group of low-molecular weight oligopeptide mixture which adopts fish skin, fish bones or fish flesh of marine fishes as main raw materials, is produced by hydrolysis through an enzyme method, can be dissolved by trichloroacetic acid, has the relative molecular mass of smaller than 1,000 and comprises marine collagen peptide (derived from the fish skin), marine bone-derived peptide (derived from the fish bones) and marine protein peptide (derived from the fish flesh). The invention has the characteristics of easy and rapid absorption, low viscosity, good water solubility, and the like. Animal tests prove that the marine peptide has the effects of promoting skin peptide wound healing after a caesarean section operation and promoting the wound healing of the uterus.
Description
Technical field
The present invention relates to a kind of marine peptide product and new purposes thereof, is the purposes of marine peptide in preparation promotion caesarean section postoperation recovery medicine, health food of extracting from marine fishes (fish skin, fishbone, the flesh of fish) specifically.Belong to medicine, health care of food field.
Background technology
Caesarean delivered basic goal is to solve difficult labour and some high risk pregnancy, saves the life that encloses living youngster and pregnant and lying-in women.Produce improvement, the progress of anaesthesia technology, the development of antibiotics of operation method along with cuing open the palace, and postoperative analgesia The Application of Technology, the safety of cuing open palace product operation is much improved, and puerpera's postoperative is painful to be reduced.Therefore more use when the women gives a birth.In addition, the primipara does not have experience to pregnancy and delivery, worry fetus in the birth process safety, have difficult labour, fear labor pain, the slack vagina that may occur after vagina operation operation, the vaginal deliveries such as the incision of worry perineum, thereby it is nervous to giving a birth, depressed and frightened, cause spontaneous labor is lacked confidence, the social mentality's ability to bear during to childbirth is relatively poor.Pregnancy and delivery high risk factor incidence rates such as lying-in woman advanced in years, placenta previa, uterine cicatrix, macrosomia, gestational hypertension, gestational diabetes increase.The palace newborn baby is clever as cuing open, the puerpera is painful few for wrong understanding comparatively general in the society, and family members are convenient or the like, even the requirement of childbirth when proposing to select lucky day lucky, therefore selects cesarean section termination of pregnancy person also more and more.
In recent years, cuing open the palace productive rate is and increases trend day by day.The peak of this trend of American-European developed country appears at the late 1970s and the beginning of the eighties, reach about 25%, though begin to make great efforts to reduce to cut open the palace productive rate in the later stage eighties, and it is stable with a slight decline in thereafter more than 10 year, but before 2000, cut open the palace productive rate and still maintain about 20%, maintain 5%～20% at present, do not reach cuing open in the palace productive rate desired value 15% of U.S. department of obstetrics and gynecology association proposition.Domesticly cut open the palace productive rate in early 1990s and reach about 20%, begin soaringly fast from the mid-90, the end of the nineties, the palace productive rate that cuts open of domestic big city hospital promptly reached 30%～40%.Though do not have at present national statistical data, most of policlinics reports cut open the palace productive rate about 40%～60%, high person even reach more than 60%～80% has the gesture that replaces vaginal delivery and become conventional childbirth options greatly.
Caesarean delivered application is more and more.But cuing open the palace product is a kind of operation after all, to parent is a kind of invasive wound, the puerpera is existed complication even dead danger in the recent period such as anesthetic accident, postoperative hemorrhage, puerperal infection, pulmonary infarction, also have long term complications such as low cesarean section incisional scar place, pregnant again back gestation, uterine rupture etc.Wherein, if poor wound healing will bring postoperative hemorrhage in the art, postoperative wound infection, disruption of wound, puerpera's ill (chronic pelvic pain, pelvic adhesion transposition disease, sterile, miscarriage of secondary) rate height, cut open palace product cicatrix gestation harm such as (CSP) to the puerpera.It is hemorrhage late period that infection of incisional wound also can cause lower uterine segment otch inflammation postoperative to occur, and severe patient septicemia occurs and jeopardizes puerpera's life.Though and it is lower to cut open palace product cicatrix gestation sickness rate, in case take place, the puerpera has the risk of mortality massive hemorrhage and uterine rupture.
Therefore, the good healing of wound in puerperal not only helps reducing post-operative complication, promotes to recover behind the cesarean section, and is particularly important to the quality of life of improving the puerpera.
And the healing of wound is the biological process of a complexity, the agglutination of skin incision is generally through 4 periods: (1) vascular reaction phase: vasoconstriction reduces hemorrhage, platelet aggregation forms blood clot, thrombokinase changes thrombinogen into thrombin, the latter makes Fibrinogen be converted into fibrin, edge of wound is combined forms the infection barrier.(2) inflammatory phase: basophilic granulocyte (mastocyte) discharges the inflammatory mediator that comprises histamine and 5-hydroxy tryptamine, causes the increase of vasodilation and cell permeability, and neutrophilic granulocyte, mononuclear cell and lymphocyte are assembled to wound surface.Blood fortune increases the removing that helps toxin and slough chip.The capillary permeability increase helps oozing out reaction, so that the wound surface of the downright bad postoperative infection of nutrition and cleansing tissue.Mononuclear phagocyte is converted into macrophage, and is with phagocyte chip and antibacterial, most important in wound healing process.Along with the increase of vasodilation and blood vessel penetration, leukocytic infiltration, the quick gathering of leukocyte and macrophage appears.The cleaning of early stage wound is to promote removing of antibacterial and allosome chip by oxygen-derived free radicals and lysosome that leukocyte discharges.This process also has a large amount of somatomedin and cytokinesis, comprises transforming growth factor (TGF-β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), interleukin-1 (IL-1), fibroblast growth factor (FGF), prostaglandin (PG), tumor necrosis factor (TNF) etc.Macrophage is the important source of these factors, and its secreted factors stimulated growth fibroblast, epithelial cell and vascular endothelial cell move in the wound.Its shortage can have a strong impact on wound healing.General 3～7d of this phase, when tissue necrosis or infection occurring, this phase can prolong and influence healing, causes cicatrization.(3) the propagation phase: this process comprises the generation of substrate product, blood vessel endothelium and epithelium, and final leukocyte is replaced by macrophage and fibroblast.Under the effect of FGF, PDGF and TGF-β, substrate that macrophage-mediated cell moves and propagation cicatrizes a wound forms, and these cells also continue to adjust the effect of combating microorganisms simultaneously.In this stage, epithelial cell begins growth, and keratin moves through wound surface around epithelium.Basement membrane slowly continues, and is closed fully until epidermal area.Main somatomedin comprises angle albuminous cell somatomedin, TGF-β, FGF, EGF and PDGF.(4) the moulding phase: this process originates in the maturity of fibroblast in substrate and the increase of concentrated quantity of wound.Fibroblast is grown under the stimulation of somatomedin, is divided and produces collagen protein and glucosamine, constitutes the extracellular framework.The moulding control of wound is attributable to the complicated adjusting process, the upset of extracellular matrix and collagen, and the increase of collagen and proceeding reaches balance at last, forms a strong stable cicatrix, and this process is sustainable to reach 2 years.
From the above, except the activity that relies on various cells, the agglutination of wound needs the comprehensive regulation of various somatomedin and cytokine, and wound is healed within a certain period of time.The factor that wherein plays a significant role has:
Transforming growth factor-beta (TGF-β): activated platelet, macrophage and lymphocyte all can produce TGF-β, the differentiation of TGF-β pair cell, hypertrophy, inflammatory process have stimulation, inhibition or biphasic effect, the synthesizing of pair cell epimatrix, reinvent and have unique effect.TGF-β not only by promoting the fibroblast chemotactic, produces collagen fiber and extracellular matrix, also can reduce the synthetic of collagenase, increases the generation of inhibitors of metalloproteinase, thereby reduces the zymolysis in the wound, promotes wound healing.
Platelet-derived growth factor (PDGF): all can synthesize PDGF the local activated platelet of wound, mononuclear cell, macrophage and fibroblast.PDGF not only has the chemotactic sucking action to fibroblast, mononuclear cell and neutrophilic granulocyte, also can stimulate fibroblast proliferation, generate substrate, express integrin receptor, move to the wound district, induce fibroblast to change to myofibroblast in the damage later stage
[10]
Fibroblast growth factor (FGF): FGF is a family, existing at present 19 members, and each member's structurally associated of FGF, functional similarity are regulated growth, secretion, migration and the apoptosis of various kinds of cell.Studies show that FGF plays a role by the mode of paracrine, early stage growth factor I L-1 is produced necessary the stimulation, and the latter plays an important role in the reparation of endothelium.
Basic FGF wherein (bFGF, FGF
2) short angiogenesis function is arranged, regulate the growth and the function thereof of cells of vascular wall; Mitogen activity and chemotaxis are arranged, can promote growth of fibroblasts, propagation, chemotactic inflammatory cell and tissue repair cell are assembled to wound surface.In addition, FGF among the FGF family member
7Claim keratinocyte growth factor (KGF) again, epidermis cell is had unique stimulation, the edge of wound epidermis and the corium KGF of in situ hybridization visible damage skin highly express, and be closely related with promoting epidermization.
If some somatomedin lacks, the synthetic and degraded balance disorder of collagen protein, will influence agglutination, cause the formation of hyperplasia and cicatrix; Perhaps slow down even stop agglutination.Hyperplasia and cicatrix appear in 5%～15% wound usually very soon after operation.Roomy and the incisional scar of the scar tissue of puerpera's wound splits and can cause cuing open the palace and produce the onset risk of cicatrix gestation and increase.Cut open the palace in addition and produce operating time, operative incision position, incision type, uterine incision suture way, postoperative wound infection, healing is bad, whole body situation factors such as (age, obesity, malnutrition, vitamin, trace element, systemic disease and medicines) all will influence wound healing process.
Collagen protein has unique filamentary structure and excellent biological compatibility, degradability and low antigenicity, and more application is in making cosmetics, biomedical material, health product etc.The external application of collagen protein has the epidermis cell of improvement microcirculation and promotes the skin peptide to organize metabolic effect, thereby quickens tissue regeneration and reparation.Zoopery and clinical experiment prove that all collagen protein can promote epidermal growth, have unique automatic repair function, can guide the epithelial cell defective region of moving into, and play when cell migration and support and lubrication.Light, the moderate acne of human collagen protein pad pastings such as Dai Gengwu treatment studies show that and can improve cutaneous circulation, and is evident in efficacy.In addition, collagen protein contains the required aminoacid of abundant cellular metabolism, can improve the living environment of Skin Cell, promotes the metabolism of skin histology.Containing multiple biologically active peptide in the collagen protein, having the hypertensin conversion enzyme activity of inhibition, suppress platelet congealing activity, antioxidant activity and anti-tumor activity etc.
Be rich in collagen protein in Fish skin and bone or the meat, the marine peptide that derives from Fish skin and bone or meat is to be the Powdered oligopeptide product of main component at the small-molecular peptides below 1000 with relative molecular mass, form by 2～6 aminoacid, be rich in collagen synthesis materials such as hydroxyproline.Not only have characteristics such as good dissolubility, low-viscosity, high concentration, water solublity, heat stability, and absorption is fast in vivo, utilization rate is high.Collagen peptide has moisture retention, therefore certain cosmetic result is arranged, and has been widely used in cosmetics.The natural materials of selecting for use in the natural materials that U.S. CTFA cosmetic material handbook is employed and the Japan's " functional cosmetics raw material " all has collagen protein and hydrolyzate collagen peptide thereof.Experiment in vitro confirms that the fish collagen peptide has stronger tyrosinase activity and suppresses ability as natural skin-lightening cosmetic raw material.Remove cosmetic field, the activity of collagen peptide at aspects such as blood pressure lowering, blood fat reducing, blood sugar regulation, antioxidation, enhancing immunity, rheumatism, strong bones also becomes the focus of people's research and development gradually.Zoopery shows that marine oligopeptide has the activity of certain blood fat reducing, blood sugar regulation, antioxidation, enhancing immunity, bone density improving.Domestic and international existing part Study has been proved marine peptide and laboratory animal has been had effects such as anti-damage and antioxidation.
In view of this, the health-care effect research to marine peptide has both at home and abroad obtained the achievement that attracts people's attention, and many marine peptide medicines and health food are come out one after another, and economic benefit is very remarkable.But at present also seldom for the research of marine peptide wound healing and rehabilitation after promoting cesarean section, if reach the function that promotes caesarean section postoperation recovery by developing drugs, health food and food, improve the effect of patient's quality of life behind the cesarean section, not only economy but also practicality will be brought very big prospect to the health-care industry of China.
Summary of the invention
The purpose of this invention is to provide a kind of marine peptide product and the purposes in preparation promotion caesarean section postoperation recovery medicine, health food thereof.
Marine peptide provided by the invention is that fish skin, the flesh of fish or the fishbone with marine fishes is primary raw material, through enzymatic hydrolysis production, can be dissolved by trichloroacetic acid, relative molecular mass is at one group of low-molecular-weight oligo peptide below 1000, comprise marine collagen (deriving from fish skin) and bone source, ocean peptide (deriving from fishbone) or sea protein peptide (deriving from the flesh of fish), have easy absorption, absorb fast, low viscosity, characteristics such as good water solubility.
Wherein said medicine, health food are powder, granule, capsule, tablet, pill, oral liquid.
Specific embodiments
The present invention is further illustrated below in conjunction with specific embodiments, and these examples should be understood that only to illustrate, but not limit the scope of the invention by any way.
Embodiment: the effect research of wound healing behind the marine collagen promotion rat cesarean section
One, materials and methods
The SD rat was 96 in pregnant 15 days, was provided by Department Of Medicine, Peking University's Experimental Animal Center, and cleaning level Animal House is raised 25 ℃ of feeding environment temperature, humidity 60%RH.Be divided into 4 groups at random, i.e. matched group, the basic, normal, high dosage group of marine collagen, 24 every group.Pregnant Mus adaptability was fed after 3 days, in the time of pregnant 19 days, matched group gives normal saline and irritates stomach, the collagen peptide group gives the marine collagen of corresponding dosage (0.13g/kgbw, 0.38g/kgbw, 1.15g/kgbw) and irritates stomach, 1% sodium phenobarbital intraperitoneal injection of anesthesia is cut off the 3cm longitudinal incision at hypogastric region along ventrimeson, opens the abdominal cavity, respectively do the longitudinal cut of 2.0cm in the uterus, both sides back to the middle part of mesentery side, extrude rat cub and Placenta Hominis.Sew up dark abdomen, fascia, peritoneum 4-0 silk suture, skin peptide 4-0 silk suture continuously with 5-0 absorbability surgery gutstring.Postoperative is coated with 2% iodine tincture, and injection penicillin 0.1ml puts back in the box, notes warmingly, and postoperative fasting 1 day is normally drunk water.Each dosage group postoperative of marine collagen continues to give the marine collagen filling stomach of corresponding dosage, and once a day, matched group gives the equal-volume normal saline and irritates stomach.
The wound situation of change is observed with magnifier every day in the operation back.Each organizes the response to traume of observing wound and surrounding tissue thereof in postoperative on the 3rd day, the healing state of the 7th, 14,21 day observation wound.Post-surgical trauma reaction and the unification of wound healing situation are marked by standard in table 1, the table 2.
The response to traume standards of grading of table 1. wound and surrounding tissue thereof
Table 2. wound healing situation standards of grading
7 days after surgery, 14 days, 21 days dead 8 rats in every component other places are measured wound skin tension and uterine rupture pressure respectively, and carry out pathological study, evaluating skin and uterine incision healing state.Wound skin tension assay method: rat is put to death in the cervical vertebra dislocation, get long 1cm, the wound skin histology of wide 0.5cm, be fixed in instrument (Pclab-UE Acquisition and Processing of Biomedical Signal, this reaches development in science and technology Co., Ltd the little letter in Beijing) two ends, draw back skin, until breaking, record tension force maximum is the wound skin tension.Uterine rupture piezometry method: rat is put to death in the cervical vertebra dislocation, take out the uterus, the conduit of instrument (Pclab-UE Acquisition and Processing of Biomedical Signal, this reaches development in science and technology Co., Ltd the little letter in Beijing) is inserted cavity of uterus, and fix in suitable position ligation.The near-end of conduit is connected with instrument, at the uniform velocity injects normal saline in cavity of uterus, oozes out until uterus explosion or liquid, and the maximum pressure that is write down is a fracture pressure.
Two, result
The perusal performance, postoperative the 3rd day, control rats wound majority has blood crusts to adhere to, the obvious edema of wound and surrounding tissue, and the edema degree of marine collagen group rat wound obviously alleviates, the scoring of wound response to traume all is higher than matched group, and wherein high dose group (1.15g/kgbw) score is apparently higher than matched group (P＜0.05) (table 3).
Postoperative is the 7th, 14,21 days wound healing perusal results show, the obvious situation of each dosage group rat wound healing of marine collagen is better than control rats, wherein high dose group (1.15g/kgbw) the 7th, 14,21 day wound healing score all apparently higher than matched group (P＜0.05) (table 4).And marine collagen group rat on average shifts to an earlier date 1.7 days than control rats wound healing time.
Table 3. is respectively organized wound response to traume situation relatively
*: compare with matched group, difference has significance (P＜0.05)
Table 4. is respectively organized the wound healing situation relatively
*: compare with matched group, difference has significance (P＜0.05)
Wound skin tension measurement result shows: each dosage group of marine collagen all can improve to be cutd open the palace and produces rat wound skin resistance to tension, wherein marine collagen high dose group (1.15g/kgbw) postoperative in the time of the 7th, 14,21 days the wound skin tension all apparently higher than matched group (P＜0.05); In dosage group (0.38g/kgbw) postoperative in the time of the 14th, 21 days rat wound skin tension apparently higher than matched group (P＜0.05) (table 5).
Table 5. marine collagen produces the influence of rat postoperative wound skin tension to cuing open the palace
*: compare with matched group, difference has significance (P＜0.05)
Uterine rupture piezometry result shows: each dosage group of marine collagen all can promote recover of uterus situation behind the rat cesarean section, show as the uterine rupture increased pressure, wherein the uterine rupture pressure of high dose group in the time of 7,14,21 days after surgery is apparently higher than matched group (P＜0.05), and 14 days uterus fracture pressures of middle dosage group rat postoperative are apparently higher than matched group (P＜0.05) (table 6).
Table 6. marine collagen produces the influence of rat postoperative uterine rupture pressure to cuing open the palace
*: compare with matched group, difference has significance (P＜0.05)
The result of histopathologic examination shows, the 7th day marine collagen group rat of postoperative wound epithelial thickness, new capillary vessel quantity are all obviously greater than matched group, collagen fiber increase, increase thick, fusion than matched group, are to be parallel to the skin surface arrangement, and inflammatory cell is less than matched group.The 14th day tissue slice of postoperative observed and shown, the newborn epidermal layer cells of dosage group and high dose group flap coverage in the marine collagen, blood capillary and fibroblast quantity have been seen minimizing in the newborn fibrous tissue, collagen contents is higher than matched group and marshalling, and the newborn epidermal layer cells of matched group is interrupted flap coverage.Postoperative the 21st day, marine collagen group wound epidermis is complete, and the scar tissue area shrinks and diminishes, and arrangement of collagen fibers is more neat, and still visible a small amount of collagen fiber are assembled bunchy in the matched group wound tissue, are the curly hair shape, arrangement disorder.Wherein 1.15g/kgbw marine collagen group effect is best.
The above results shows: marine collagen has and promotes skin wound healing behind the cesarean section, increases skin wound tensile strength, can promote uterus wound healing behind the cesarean section simultaneously, increases the effect of uterus resistance to fracture pressure behind the cesarean section.
Claims (4)
1. marine peptide is preparing the purposes that promotes in caesarean section postoperation recovery medicine, the health food.
2. as claim 1, wherein said marine peptide is that fish skin, the flesh of fish or the fishbone with marine fishes is primary raw material, through enzymatic hydrolysis production, can be dissolved by trichloroacetic acid, relative molecular mass is at one group of low-molecular-weight oligo peptide below 1000, have easy absorption, absorb fast, low viscosity, characteristics such as good water solubility.
3. as claim 1, wherein said medicine, health food are powder, granule, capsule, tablet, pill, oral liquid.
4. as claim 1, wherein said caesarean section postoperation recovery is meant operation wound healing and uterine incision healing behind the cesarean section.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102366042A (en) * | 2011-10-29 | 2012-03-07 | 山西振东五和健康食品股份有限公司 | Nutritious powder for postoperative aftercare |
| CN110558567A (en) * | 2018-06-06 | 2019-12-13 | 江中药业股份有限公司 | Composition for promoting postoperative wound healing and preparation method thereof |
| CN110935003A (en) * | 2019-12-30 | 2020-03-31 | 河北北方学院附属第一医院 | Biological polypeptide composition for promoting skin injury repair |
| CN111388740A (en) * | 2020-05-21 | 2020-07-10 | 南通大学 | Wound healing promoting dressing and preparation method thereof |
| CN117562979A (en) * | 2023-11-20 | 2024-02-20 | 山东大学齐鲁医院 | Biological agent for treating preeclampsia syndrome |
-
2009
- 2009-02-06 CN CN200910008620A patent/CN101797373A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102366042A (en) * | 2011-10-29 | 2012-03-07 | 山西振东五和健康食品股份有限公司 | Nutritious powder for postoperative aftercare |
| CN102366042B (en) * | 2011-10-29 | 2013-01-23 | 山西振东五和健康食品股份有限公司 | Nutritious powder for postoperative aftercare |
| CN110558567A (en) * | 2018-06-06 | 2019-12-13 | 江中药业股份有限公司 | Composition for promoting postoperative wound healing and preparation method thereof |
| CN110558567B (en) * | 2018-06-06 | 2023-10-27 | 江中药业股份有限公司 | Composition for promoting postoperative wound healing and preparation method thereof |
| CN110935003A (en) * | 2019-12-30 | 2020-03-31 | 河北北方学院附属第一医院 | Biological polypeptide composition for promoting skin injury repair |
| CN110935003B (en) * | 2019-12-30 | 2021-01-08 | 北医博大(北京)皮肤病医学研究院有限公司 | Biological polypeptide composition for promoting skin injury repair |
| CN111388740A (en) * | 2020-05-21 | 2020-07-10 | 南通大学 | Wound healing promoting dressing and preparation method thereof |
| CN111388740B (en) * | 2020-05-21 | 2021-09-10 | 南通大学 | Wound healing promoting dressing and preparation method thereof |
| CN117562979A (en) * | 2023-11-20 | 2024-02-20 | 山东大学齐鲁医院 | Biological agent for treating preeclampsia syndrome |
| CN117562979B (en) * | 2023-11-20 | 2024-05-28 | 山东大学齐鲁医院 | Biological agent for treating preeclampsia syndrome |
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Application publication date: 20100811 |