CN104606183A - Postoperative anti-adhesion product as well as preparation method and application thereof - Google Patents

Postoperative anti-adhesion product as well as preparation method and application thereof Download PDF

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Publication number
CN104606183A
CN104606183A CN201510025776.3A CN201510025776A CN104606183A CN 104606183 A CN104606183 A CN 104606183A CN 201510025776 A CN201510025776 A CN 201510025776A CN 104606183 A CN104606183 A CN 104606183A
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adhesion
polyethylene glycol
andrographolide
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postoperative
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CN104606183B (en
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杨宝峰
朴贤美
杜智敏
张妍
朱久新
吴立军
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Harbin Engineering University
Harbin Medical University
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Harbin Medical University
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Abstract

The invention discloses a postoperative anti-adhesion product as well as a preparation method and an application thereof. The postoperative anti-adhesion product comprises an effective component and a solvent, wherein the effective component consists of andrographolidume and polyethylene glycol, and the solvent is normal saline. Research indicates that the postoperative anti-adhesion product can effectively prevent postoperative adhesion, tissue can be lubricated, the number of leukocytes and release of inflammatory factors in inflammatory reactions can be inhibited, and compared with commercially available anti-adhesion products, the postoperative anti-adhesion product is lower in toxicity. The postoperative anti-adhesion product has the broad clinical application prospect.

Description

A kind of post-operation adhesion preventing product and its production and use
Technical field
The present invention relates to a kind of post-operation adhesion preventing product and its production and use, particularly a kind of post-operation adhesion preventing product containing andrographolide and Polyethylene Glycol and its production and use.The invention belongs to medical equipment technical field.
Background technology
Along with the continuous progress of science and technology, what the techniques and methods that modern surgery is performed the operation also was making rapid progress advances, but the complication that abdominal postoperative intestinal adhesion is common after being still abdominal.There are some researches show: accept 1.2% in the patient of minor operation in abdominal part and accept 3.6% in major abdominal surgery patient, needing operative treatment again because of postoperative intestinal adhesion, so that form severe vicious cycle, finally have to carry out intestinal arrangement.This not only causes considerable distress to patient, also brings extreme difficulties to treatment.
The reason of postoperative intestinal adhesion is caused to have many, what wherein obtain extensively approval is the peritoneal surface damage caused by the implantation of mechanical injuries, tissue ischemia, exogenous material and peritonitis, cause plasminogen activator activity suppressed, Fibrinogen release increases, a large amount of fibrin deposition or fibrinolytic impairment, form network structure at organ surface, later fibroblast constantly invades and breeds, and finally causes the formation of adhesion.What therefore how to prevent postoperative intestinal adhesion becomes key issue urgently to be resolved hurrily.At present, prevent in intestinal adhesion, there is a lot of research at patient's Post operation both at home and abroad, tissue adhesion flat products on market mainly comprises: hyaluronic acid sodium gel, polylactic acid membrane, anti-sticking poly lactic acid gel, medical chitose and large clear biochargeable paper (absorbable hemostatic film) etc., but all there is problem in various degree in these products while playing to a certain degree tissue adhesion effect, hyaluronic acid sodium gel is i.e. all degradeds in 1-2 days in vivo, film property is poor, is not suitable for use in anti.The degraded of polylactic acid membrane is slow, causes burden to body, and needs stitching fixing, uses inconvenience.
Andrographolide be natural plants Herba Andrographis mainly contain effective constituent, there is thermal detoxification of dispelling, effect of anti-inflammatory analgetic, have special efficacy to bacillary with viral upper respiratory tract infection and dysentery, be described as natural antibiotics medicine.Bibliographical information andrographolide has obvious antiinflammatory action, significantly can suppress increasing of dimethylbenzene, histamine and acetic acid induced mice skin and abdominal cavity capillary permeability, the inflammatory exudation liquid measure of rat caused by obvious less Oleum Tiglii, obviously suppresses the development of foot swelling caused by rat Ovum Gallus domesticus album.Further research finds that andrographolide can excited Pituitary Adrenalcortical systemic-function specifically, both the release of ACTH can have been promoted, can increase again the biosynthesis of ACTH in antepituitary, this effect of andrographolide may be one of Main Function principle of its antiinflammatory action.Polyethylene Glycol (PEG) is a kind of purposes and pharmaceutic adjuvant widely thereof.Along with demand and the pharmaceutical preparation diversification of clinical application, Polyethylene Glycol obtains at medicine and hygiene fields and applies widely.Be processed into coupling body preparation with the character of Polyethylene Glycol self and the medicine with different pharmacological action and can not only improve its drug effect, also can alleviate the toxicity of medicine, increase bioavailability, reduce drug dose.Polyethylene Glycol also contributes to prolong drug release time in vivo, and can be used as cosolvent and improve the dissolubility of medicine hard to tolerate to strengthen its curative effect.And Polyethylene Glycol itself has certain lubricity, but visceral surface keeps lubrication, prevents visceral adhesion.The new opplication of Polyethylene Glycol in pharmaceutical preparation has obtained the extensive accreditation of academia.
Andrographolide and Polyethylene Glycol proportioning compositions have good biocompatibility, suitable tissue adherence (do not need sew up), can wound coverage surface and have retention time in enough bodies completely; Can degraded and absorbed and do not need second operation to be taken out; Can effectively prevent Adhesion formation from not affecting again the normal healing of wound, there is certain mechanical strength and be convenient to implementation and operation, and andrographolide polyethylene glycol composition shows good antiinflammatory action, leukocytic number in inflammation-inhibiting reaction, and the release of inflammatory factor.To compare toxicity lower with similar anti product.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of product of post-operation adhesion preventing, effectively can prevent tissue adhesion, and can lubricates tissue, inflammation-inhibiting.
In order to achieve the above object, present invention employs following technical scheme:
A kind of post-operation adhesion preventing product of the present invention, comprises effective ingredient and solvent, and wherein, described effective ingredient is made up of andrographolide and Polyethylene Glycol, and described solvent is normal saline.
In the present invention, preferably, by weight percentage, the percetage by weight shared by each composition is andrographolide 0.05-10%, Polyethylene Glycol 5-50%, and all the other are normal saline.
Preferred, by weight percentage, the percetage by weight shared by each composition is andrographolide 5%, Polyethylene Glycol 40%, normal saline 55%.
In the present invention, preferably, the relative molecular weight of described Polyethylene Glycol is 400-20000.
Research shows, to performing the operation caused by the damage that causes, blood capillary oozes out product of the present invention, tissue fluid is oozed out, blood capillary proliferation, fibroblast and interstitial cell hyperplasia etc. can effectively suppress, lubrication is had to human internal organ, and can effective inflammation-inhibiting.
In addition, a kind of post-operation adhesion preventing product of the present invention is not degraded in vivo, can excrete after a period of time with original shape, through clinical trial certificate, without any side effects, and has good post-operation adhesion preventing effect.
Therefore, further, the post-operation adhesion preventing product that the invention allows for described in above any one is preparing the purposes in the apparatus or medicine preventing tissue adhesion, lubricates tissue and inflammation-inhibiting.
Detailed description of the invention
Further describe the present invention below in conjunction with specific embodiment, advantage and disadvantage of the present invention will be more clear along with description.But embodiment is only exemplary, does not form any restriction to scope of the present invention.It will be understood by those skilled in the art that and can modify to the details of technical solution of the present invention and form or replace down without departing from the spirit and scope of the present invention, but these amendments and replacement all fall within the scope of protection of the present invention.
The preparation of embodiment 1 post-operation adhesion preventing product
1, andrographolide 5g, Polyethylene Glycol 145040g is taken respectively;
2, andrographolide is dissolved in 55g normal saline, then adds Polyethylene Glycol, stir, can use after loading sterilizing containers.
The preparation of embodiment 2 post-operation adhesion preventing product
1, andrographolide 1g, PEG 8000 45g is taken respectively;
2, andrographolide is dissolved in 54g normal saline, then adds Polyethylene Glycol, stir, can use after loading sterilizing containers.
The preparation of embodiment 3 post-operation adhesion preventing product
1, andrographolide 10g, PEG3350 10g is taken respectively;
2, andrographolide is dissolved in 80g normal saline, then adds Polyethylene Glycol, stir, can use after loading sterilizing containers.
Experimental example 1: anti-blocking compositions prepared by different molecular weight Polyethylene Glycol and andrographolide suppresses the pharmacodynamic study of adhesion
Method:
1. SD rat 70 is divided into following group at random: Normal group, model control group, positive controls, andrographolide group, PEG400+andrographolide group, cetomacrogol 1000+andrographolide group, Polyethylene Glycol 1450+ andrographolide group, PEG400 group, cetomacrogol 1000 group, Polyethylene Glycol 1450 groups, specifically divides into groups in table 1.Polyethylene Glycol+andrographolide group post-operation adhesion preventing product is prepared in accordance with the following methods: be dissolved in by andrographolide 5g in 55g normal saline, then add Polyethylene Glycol 40g, stir, and can use after loading sterilizing containers.Polyethylene Glycol in Polyethylene Glycol group is all made into the normal saline solution use of 40%, and in andrographolide group, andrographolide is made into the normal saline solution use of 5%.
Table 1
2., after the equal fasting 12h of each treated animal, with 3% pentobarbital sodium (45mg/kgBW) intraperitoneal injection of anesthesia, after Animal Anesthesia, dorsal position is fixed.
3. abdominal part center depilation, depilation place and surrounding skin Iodophors and the sterilization of medical alcohol cotton balls, in work, hypogastric region otch, is about 3cm, find caecum at iliac fossa place after entering abdomen, occur tip-like petechia on ileocecus right flank blade placenta percreta to surface of repeatedly swiping.Often organizing rat cecal wound surface smearing dose is 2ml/.
After 4.7 days, animal sacrificed by exsanguination, each group is carried out adhesion classification by following standard:
0 grade: without adhesion.
I level: adhesion is easily from separate tissue.
II level: adhesion is not easily separated
III grade: adhesion destroys placenta percreta and just can be separated.
IV: and stomach wall, internal organs in abdomen, omentum majus etc. condense together, and can not be separated.
The results are shown in Table 2.
Table 2 respectively group adhesion scoring median compares
Each group of adhesion classification median compares * p < 0.05, n=12 with model group
Experimental example 2: the pharmacodynamic study of anti-blocking compositions inflammation-inhibiting prepared by different molecular weight Polyethylene Glycol and andrographolide
Method:
1. SD rat 70 is divided into following group at random: Normal group, model control group, positive controls, andrographolide group, PEG400+andrographolide group, cetomacrogol 1000+andrographolide group, Polyethylene Glycol 1450+ andrographolide group, PEG400 group, cetomacrogol 1000 group, Polyethylene Glycol 1450 groups, concrete grouping and Pharmaceutical formulations are with experimental example 1.
2., after the equal fasting 12h of each treated animal, with 3% pentobarbital sodium (45mg/kgBW) intraperitoneal injection of anesthesia, after Animal Anesthesia, dorsal position is fixed.
3. abdominal part center depilation, depilation place and surrounding skin Iodophors and the sterilization of medical alcohol cotton balls, in work, hypogastric region otch, is about 3cm, find caecum at iliac fossa place after entering abdomen, occur tip-like petechia on ileocecus right flank blade placenta percreta to surface of repeatedly swiping.Often organizing rat cecal wound surface smearing dose is 2ml/.
After 4.7 days, animal carotid artery sacrificed by exsanguination, opens abdominal cavity, squeezes into 5ml normal saline in abdominal cavity, and folder closes abdominal cavity, and evenly shake rat 2 minutes, opens abdominal cavity, and extract intraperitoneal liquid 2ml, on numeration of leukocyte instrument, leukocyte counts amount, the results are shown in Table 3.And apply rat interleukin-6 ELISA kit the content of interleukin-6 in each group of rat abdominal cavity liquid is detected, the results are shown in Table 4.
Table 3 respectively group numeration of leukocyte compares
Each group of leukocyte count compares * p < 0.05, n=12 with model group
Table 4 is group interleukin-6 comparision contents respectively
Each group of interleukin-6 content compares * p < 0.05, n=12 with model group
Experimental example 3: compositions prepared by different molecular weight Polyethylene Glycol and andrographolide suppresses the pharmacodynamic study of adhesion and inflammation associated pathology index
Method:
1. SD rat 70 is divided into following group at random: Normal group, model control group, positive controls, andrographolide group, PEG400+andrographolide group, cetomacrogol 1000+andrographolide group, Polyethylene Glycol 1450+ andrographolide group, PEG400 group, cetomacrogol 1000 group, Polyethylene Glycol 1450 groups, concrete grouping and each group Pharmaceutical formulations are shown in experimental example 1.
2., after the equal fasting 12h of each treated animal, with 3% pentobarbital sodium (45mg/kgBW) intraperitoneal injection of anesthesia, after Animal Anesthesia, dorsal position is fixed.
3. abdominal part center depilation, depilation place and surrounding skin Iodophors and the sterilization of medical alcohol cotton balls, in work, hypogastric region otch, is about 3cm, find caecum at iliac fossa place after entering abdomen, occur tip-like petechia on ileocecus right flank blade placenta percreta to surface of repeatedly swiping.Often organizing rat cecal wound surface smearing dose is 2ml/.
After 4.7 days, animal carotid artery sacrificed by exsanguination, opens abdominal cavity, and get rat wound site 2cm intestinal tube tissue, normal saline is fixed with formalin after cleaning content immediately, specimens paraffin embedding slices, hematoxylin-eosin staining, light Microscopic observation., fibroblast and interstitial cell hyperplasia degree how many according to inflammatory cell, exist with or without fibrin, mesothelial cell and the situation such as arrangement of collagen fibers, blood capillary proliferation, judge adhesion degree.Experimental result is as follows:
(1) model control group: have a large amount of fibroblasts and inflammatory cell infiltration, tissue edema is obvious; Serosal surface proliferation of fibrous tissue is obvious, and fiber adhesion is serious, and placenta percreta has lymphocyte to be dispersed in infiltration, thin vessels showed increased, and fibroblast proliferation enlivens, collagen fiber dense arrangement;
(2) positive controls: have inflammatory cell infiltration, fibroblast is less, tissue edema, collagen fiber dense arrangement, and hypertrophy appears in fibrous tissue and thin vessels, and serosal surface has endothelium and epithelial hyperplasia;
(3) Polyethylene Glycol+andrographolide group: only have a small amount of fibroblast infiltration and inflammatory cell infiltration, organize Mild edema, serosal surface has monolayer mesothelial cell hypertrophy.Fibrous tissue and thin vessels hypertrophy not obvious.Collagen fiber loosen.Wherein, the lightest with Polyethylene Glycol 1450+ andrographolide group inflammatory infiltration degree.
Experimental example 4: the anxious poison experiment of different molecular weight Polyethylene Glycol
Choose the Polyethylene Glycol of molecular weight at 400-20000: PEG1450, PEG3350, PEG4000, PEG6000, PEG8000, be divided into 5 processed group.Kunming mouse 150, body weight 20-25g, male and female half and half.Often organize each 15 mices of male and female.Polyethylene Glycol is all made into 40% normal saline solution, and the classical assay method horn method according to LD50 sets each group, is 100ml/kg, 46.4ml/kg, 21.5ml/kg, 10ml/kg, 4.64ml/kg.Intraperitoneal injection, administration volume is 0.2ml/10g.Experimental result is as shown in table 5 below:
Table 5
Result shows PEG1450, and PEG3350, PEG4000, PEG6000, PEG8000 acute toxicity index LD50 value is bigger than normal with commercially available anti product, and PEG anti product toxicity is described, and comparatively commercially available prod is low.
The experimental result of above experimental example 1-4 shows: post-operation adhesion preventing product of the present invention has the clear and definite effect preventing tissue adhesion, lubricates tissue and inflammation-inhibiting, and especially in anti, inflammation-inhibiting aspect is better than commercially available prod.

Claims (5)

1. a post-operation adhesion preventing product, comprises effective ingredient and solvent, it is characterized in that: described effective ingredient is made up of andrographolide and Polyethylene Glycol, and described solvent is normal saline.
2. post-operation adhesion preventing product according to claim 1, is characterized in that: by weight percentage, and the percetage by weight shared by each composition is andrographolide 0.05-10%, Polyethylene Glycol 5-50%, and all the other are normal saline.
3. post-operation adhesion preventing product according to claim 2, is characterized in that: by weight percentage, and the percetage by weight shared by each composition is andrographolide 5%, Polyethylene Glycol 40%, normal saline 55%.
4. the postoperative antiseized product according to any one of claim 1-3, is characterized in that: the relative molecular weight of described Polyethylene Glycol is 400-20000.
5. the post-operation adhesion preventing product described in any one of claim 1-4 is preparing the purposes in the apparatus or medicine preventing tissue adhesion, lubricates tissue and inflammation-inhibiting.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1371692A (en) * 2001-02-20 2002-10-02 周广刚 Medicine for preventing tissue from adhersion after operation
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CN102018706A (en) * 2009-09-15 2011-04-20 周广刚 Postoperative anti-adhesion medicament
CN102056627A (en) * 2008-06-12 2011-05-11 詹森药业有限公司 Use of histamine H4 antagonist for the treatment of post-operative adhesions

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1371692A (en) * 2001-02-20 2002-10-02 周广刚 Medicine for preventing tissue from adhersion after operation
CN101366723A (en) * 2007-08-16 2009-02-18 侯骏骥 Medicinal composition
CN102056627A (en) * 2008-06-12 2011-05-11 詹森药业有限公司 Use of histamine H4 antagonist for the treatment of post-operative adhesions
CN102018706A (en) * 2009-09-15 2011-04-20 周广刚 Postoperative anti-adhesion medicament

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
吕巧莉等: "《穿心莲内酯的研究进展及临床应用》", 《南昌大学学报(医学版)》 *
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