CN102441007A - Bladder perfusate containing composite components - Google Patents

Bladder perfusate containing composite components Download PDF

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Publication number
CN102441007A
CN102441007A CN2010105022719A CN201010502271A CN102441007A CN 102441007 A CN102441007 A CN 102441007A CN 2010105022719 A CN2010105022719 A CN 2010105022719A CN 201010502271 A CN201010502271 A CN 201010502271A CN 102441007 A CN102441007 A CN 102441007A
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concentration
bladder
irrigation
liquid
chitosan
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CN2010105022719A
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顾其胜
马贤鹏
付爱玲
周宁辉
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SHANGHAI JINGFENG PHARMACEUTICAL CO Ltd
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SHANGHAI JINGFENG PHARMACEUTICAL CO Ltd
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Abstract

The invention provides bladder perfusate containing composite components. The bladder perfusate comprises sodium hyaluronate with a concentration of 0.5 to 1%, chitosan with a concentration of 0.1 to 0.8% and normal saline balanced liquid. Since sodium hyaluronate can participate in repair and chitosan can inhibit bacteria and relieve pain, the bladder perfusate provided in the invention not only can participate in in-situ tissue repair, but also can inhibit bacteria and relieve pain in treating interstitial cystitis.

Description

The irrigation of bladder liquid of composite parts
Technical field
The present invention relates to a kind of irrigation of bladder liquid that is combined into.
Background technology
In recent years, the research of the layer of the glycosaminoglycans (GAG) in the mucous membrane of urinary bladder has obtained certain progress.The damage that interstitial cystitis (IC) (that is: a kind of chronic inflammatory disorders with pain of wall of urinary bladder), bacterial cystitis etc. come to light with the GAG layer has certain relation.Glass acid is the main mucopolysaccharide composition in most of histiocyte epimatrixs, is distributed widely in the body tissue liquid, and it also is an important composition composition in the GAG layer of bladder top layer.Experimental data shows, has obtained good effect with hyaluronic acid sodium solution treatment intractable inflammation, a matter property, bacterial cystitis.
At present, Cystistat (the being the hyaluronic acid sodium composition merely) product that has Canadian Bioniche pharmacy Group Co.,Ltd to produce abroad: aseptic hyaluronic acid sodium liquid.Being the hyaluronic acid sodium that first research and development of the whole world are used to treat bladder disease, also is simultaneously the aseptic hyaluronic acid sodium solution of present domestic and international unique non-animal source property, can be used for repairing the damaged glucosaminoglycan layer of bladder inwall (GAG layer) temporarily.Its properties of product structure and composition: this product is made up of hyaluronic acid sodium, sodium chloride, sodium dihydrogen phosphate, monovalence sodium hydrogen phosphate, water for injection.Its scope of application: this product is used for interim the substituting that urothelium glucosaminoglycan layer (GAG) protective layer lacks.
Interstitial cystitis is that one deck inner membrance is impaired in the urothelium, causes the infringement of many harmful substances, and damaged tissues is inflamed.Therefore, outside its natural materials-hyaluronic acid sodium is repaired, very important also to pay close attention to two problems:
Figure 959606DEST_PATH_IMAGE001
interstitial cystitis is a kind of chronic pelvic pain disease, and it can cause the pain of uncomfortable or the bladder and the pelvic cavity near zone of persistence.Therefore, pain relieving is one of the therapeutic goal that must consider, is optimum if any the composition of certain analgesic effect.
many cystitis; Especially bacterial cystitis, its cause of disease is the antibacterial that causes disease.If the composition of bacteriostasis antibiosis is arranged in it is repaired, its effect is not only Zhi Biao but effects a permanent cure.
Summary of the invention
Be merely single component in order to overcome existing irrigation of bladder liquid; It is not enough to participate in antibacterial analgesic; The present invention provides a kind of irrigation of bladder liquid of composite parts, and this irrigation of bladder liquid can not only be treated interstitial cystitis (IC) and participated in the original position tissue repair, can also antibacterial pain relieving.
Technical scheme of the present invention is: the irrigation of bladder liquid of composite parts; Form by hyaluronic acid sodium (concentration is 0.5-1%), chitosan (antibacterial pain relieving) (concentration 0.1-0.8%) and normal saline balance liquid; Because of hyaluronic acid sodium can participate in repairing; Chitosan can antibacterial pain relieving, can participate in the purpose that the original position tissue repair again can antibacterial pain relieving ground treatment interstitial cystitis (IC) thereby reach.
The specific embodiment
Hyaluronic acid sodium has two important parameters in interpolation composition of the present invention, that is, and and the content in solution (concentration) and its quality (molecular weight).
1, concentration, concentration is one of key parameter in prescription.Concentration is low, and it is not enough to get into bladder layer coverage rate, and effect is not good enough; Concentration is too high, and solution is thickness very, can not be evenly distributed on internal layer.Therefore, grope and verify that a suitable concentration is very important.
2, molecular weight, glass acid are straight chain polymer chemical compounds, its effect of decision of the size of its molecular weight and with the concentration phase relation.Molecular weight is low, disperses sparse at solution state.If concentration does not reach certain value, effect is bad.But the concentration height shows very thickness again.Therefore, grasp certain molecular weight ranges, cooperate above-mentioned concentration just can reach optimum efficiency.
We draw through experiment:
1. hyaluronic acid sodium concentration because of glass acid in the urothelium layer should contain higher concentration, adopts 0.4% concentration at 0.5-1% abroad, and present inventor's research shows should be more than 0.5%, and concentration range is at 0.5-1%, and optium concentration is at 0.65-0.7%;
2. the hyaluronic acid sodium molecular weight should be more than 500,000, and scope is at 50-200 ten thousand, and optimum weight is at 100-120 ten thousand.
Chitosan is the polycation polysaccharide of a special nature because of it; Influence its performance and curative effect three factors are arranged; That is: concentration (content in solution), deacetylation (positive charge that exposes in the molecule what) and molecular weight (size of molecular mass) specify as follows:
1, concentration contains the chitosan molecule of some in solution, be directly related to its effect.Concentration is low, and antibacterial analgesic effect is not good; Concentration is too high, and viscosity strengthens, and influences its performance function.Suitable concentration competence exertion optimum efficiency.
2, deacetylation, how much positively charged on the pain relieving of chitosan and antibacterial and its molecule have a direct relation, and the amount that strengthens positive charge can significantly improve its pain relieving and fungistatic effect.
3, molecular weight, in solution, its molecular mass is the radix that exposure positive charge and solution concentration are associated.Therefore, require certain molecular weight, just can be equipped with certain concentration value, really reach optimum curative effect.
The chitosan antifungal mechanism:
Existing lot of documents and related data research both at home and abroad shows that the present inventor also did a large amount of experiments and shows 5.:
Its positive surface charge of high molecular weight chitosan mat combines with the bacterium surface negative charge; Changed the antibacterial permeability; The intravital material of antibacterial is leaked, and full-bodied chitosan of while has hindered nutrient substance again to be caused the antibacterial apoptosis and then plays bacteriostasis to the inner supply of bacterial body.And low-molecular weight chitoglycan can infiltrate in the bacterial body, combines and suppress mRNA and proteinic synthetic with DNA, transcribes and then play bacteriostasis thereby suppressed DNA.
At home and abroad in the document so far still needleless to glass acid bacteriostatic research report; But theoretically; As the HMW carbohydrate of an anion glycosaminoglycans, obviously under high concentration, can cause certain obstacle to the antibacterial diffusion, but along with its effect of lowering of concentration just disappears.Experimental result is following:
Figure 95632DEST_PATH_IMAGE003
Annotate:
Figure 615475DEST_PATH_IMAGE004
in the table+expression has inhibitory action, ++ expression has strong inhibitory action;
In
Figure 492164DEST_PATH_IMAGE005
table-expression unrestraint effect ,+-to be illustrated under HMW, the high concentration bacterial growth slow;
Figure DEST_PATH_IMAGE006
chitosan HMW is more than 300,000, and the chitosan low-molecular-weight is below 10,000;
The acid of
Figure 753775DEST_PATH_IMAGE007
glass is that HMW is more than 1,000,000 (concentration is 1%);
Draw through experiment:
Figure DEST_PATH_IMAGE008
chitosan concentration should be greater than 0.1%; Scope is at 0.1-0.8%, and optium concentration is at 0.3-0.5%;
Figure 635188DEST_PATH_IMAGE005
deacetylating degree of chitosan should be greater than 50%; Scope is at 50-98%, and best deacetylation is 90%;
Figure 961651DEST_PATH_IMAGE006
the chitosan molecule amount should be greater than 100,000; Scope is at 10-50 ten thousand, and is best at 20-30 ten thousand.
Because of the PH fluctuation range of people's body fluid at 6.8-7.5, its zwitterion is in poised state.For the irrigation of bladder liquid that makes this composite parts is brought into play curative effect better, therefore need its osmotic pressure and PH are controlled.Normal saline is the sodium chloride solution that physiology or osmotic pressure commonly used clinically equate with human plasma, and wherein the osmotic pressure value of 0.9% sodium chloride solution and normal person's blood plasma, tissue fluid all are much the same.Its purposes is for supplying with electrolyte and the tension force of keeping body fluid.There are bicarbonate system, sodium phosphate system and hemoglobin and plasma protein system in the system that regulates acid-base balance in the human body.What the present inventor adopted is that buffer solution is prepared by the sodium phosphate system, that is, and and the mixed liquor of sodium dihydrogen phosphate (2 water) and sodium hydrogen phosphate (12 water).
We draw through experiment:
Figure DEST_PATH_IMAGE008A
normal saline balance liquid is made up of sodium chloride (concentration is 0.9%), sodium dihydrogen phosphate (2 water) (concentration is 0.004%), sodium hydrogen phosphate (12 water) (concentration is 0.028%) and water for injection.
The PH of normal saline balance liquid is controlled in the 7.1-7.5 scope.

Claims (9)

1. the irrigation of bladder liquid of a composite parts is characterized in that being made up of concentration 0.5 ~ 1% hyaluronic acid sodium, concentration 0.1 ~ 0.8% chitosan and normal saline balance liquid.
2.. the irrigation of bladder liquid of composite parts as claimed in claim 1, the concentration that it is characterized in that said hyaluronic acid sodium is 0.65 ~ 0.7%.
3. the irrigation of bladder liquid of composite parts as claimed in claim 1, the molecular weight ranges that it is characterized in that said hyaluronic acid sodium is 50 ~ 2,000,000.
4. like the irrigation of bladder liquid of claim 1 or 3 described composite partss, the molecular weight ranges that it is characterized in that said hyaluronic acid sodium is 100 ~ 1,200,000.
5. the irrigation of bladder liquid of composite parts as claimed in claim 1, the concentration that it is characterized in that said chitosan is 0.3 ~ 0.5%.
6. the irrigation of bladder liquid of composite parts as claimed in claim 1, the molecular weight that it is characterized in that said chitosan is 10 ~ 500,000, deacetylation is 50 ~ 98%.
7. like the irrigation of bladder liquid of claim 1 or 6 described composite partss, the molecular weight that it is characterized in that said chitosan is 20 ~ 300,000, and deacetylation is 90%.
8. the irrigation of bladder liquid of composite parts as claimed in claim 1 is characterized in that described normal saline balance liquid is that 0.9% sodium chloride, concentration are that 0.004% sodium dihydrogen phosphate (2 water), concentration are that 0.028% sodium hydrogen phosphate (12 water) and water for injection are formed by concentration.
9. the irrigation of bladder liquid of composite parts as claimed in claim 1 is characterized in that the PH of described normal saline balance liquid is controlled in the 7.1-7.5 scope.
CN2010105022719A 2010-10-11 2010-10-11 Bladder perfusate containing composite components Pending CN102441007A (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103655601A (en) * 2013-12-31 2014-03-26 上海建华精细生物制品有限公司 Combination used for bladder irrigation
CN103816543A (en) * 2013-12-10 2014-05-28 上海景峰制药股份有限公司 Preparation method for phosphate buffer solution
RU2519010C1 (en) * 2013-03-20 2014-06-10 Общество с ограниченной ответственностью "КОЛЕТЕКС" Composition for treating cystitis
CN103861091A (en) * 2014-03-20 2014-06-18 辽宁亿灵科创生物医药科技有限公司 Medicine composition for treating urocystitis
CN104940221A (en) * 2015-05-13 2015-09-30 北京大清生物技术有限公司 Composition for repairing epithelial injury of bladders and urinary tracts

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2519010C1 (en) * 2013-03-20 2014-06-10 Общество с ограниченной ответственностью "КОЛЕТЕКС" Composition for treating cystitis
CN103816543A (en) * 2013-12-10 2014-05-28 上海景峰制药股份有限公司 Preparation method for phosphate buffer solution
CN103655601A (en) * 2013-12-31 2014-03-26 上海建华精细生物制品有限公司 Combination used for bladder irrigation
CN103655601B (en) * 2013-12-31 2019-10-25 上海建华精细生物制品有限公司 A kind of composition for Intravesical instillation
CN103861091A (en) * 2014-03-20 2014-06-18 辽宁亿灵科创生物医药科技有限公司 Medicine composition for treating urocystitis
CN103861091B (en) * 2014-03-20 2016-04-27 辽宁亿灵科创生物医药科技有限公司 The pharmaceutical composition for the treatment of cystitis
CN104940221A (en) * 2015-05-13 2015-09-30 北京大清生物技术有限公司 Composition for repairing epithelial injury of bladders and urinary tracts

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Application publication date: 20120509