CN106902344A - It is a kind of to treat Chinese medicine composition of glaucoma and application thereof - Google Patents

It is a kind of to treat Chinese medicine composition of glaucoma and application thereof Download PDF

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Publication number
CN106902344A
CN106902344A CN201510966428.6A CN201510966428A CN106902344A CN 106902344 A CN106902344 A CN 106902344A CN 201510966428 A CN201510966428 A CN 201510966428A CN 106902344 A CN106902344 A CN 106902344A
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chinese medicine
collagen
medicine composition
glaucoma
active ingredient
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邵杰
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Abstract

The invention discloses a kind of Chinese medicine composition for treating glaucoma, by collagen and stimulate the menstrual flow, go screen, step-down class Chinese medicine to constitute, belong to the field of Chinese medicines.The bulk drug of the Chinese medicine composition active ingredient is stimulated the menstrual flow for collagen and ergcibe obtusifolia, betel nut, ginkgo leaf etc., removes screen, step-down class Chinese medicine, and is combined prior art and be made various eye-drops preparations.The technical scheme it is creative collagen and Effective Component of Chinese Medicine are combined to be applied in eye-drops preparations, the range of application for expanding collagen achieves preferable effect in terms of various glaucomas are treated.

Description

It is a kind of to treat Chinese medicine composition of glaucoma and application thereof
Technical field
The present invention relates to a kind of Chinese medicine composition for treating glaucoma, by collagen and stimulate the menstrual flow, go screen, step-down class Chinese medicine to constitute, belong to the field of Chinese medicines.
Background technology
Glaucoma is a kind of common disease of ophthalmology, and harm visual function is also one of most common diseases causing blindness greatly, can bring the pain of blindness to patient for various reasons.The common intraocular pressure of glaucoma increases and with circumcorneal injection, the symptom such as mydriasis, visual acuity, headache, n and V.The intraocular pressure of glaucoma has exceeded eyeball inner tissue, during the limit that especially retina can bear, then can bring the functional lesion of eyes, and great pain is brought to many patients.Chinese medicine under equal conditions, there is its distinctive feature when these diseases are treated.Chinese medicine nature and flavor theoretical level summarises the universal law of efficacy of drugs, successfully directs each section's clinical practice prescription medicine, serves certain therapeutic effect.
Collagen is containing peptide matters as obtained in the skin of animal, bone or heel string through hydrolysis or mode of action, it is to constitute the important protein of animal connective tissue, connective tissue is in addition to containing 60 70% moisture, collagen account for about 20 30%, it is the important extracellular matrix components of human body, with the good biological characteristics such as excellent fibre-forming performance, anthemorrhagic performance, cell-cell interaction performance, promotion wound healing and tissue repair；Normal function is exercised to cell, tissue or even organ and has to wound reparation significant impact, bootable epithelial cell is moved into defective region, in cell migration from lubrication；It is that neonatal cell synthesizes the matrix for utilizing, while there is AC to act on, strengthens neonatal cell adhesive attraction；Collagen between filling neonatal cell can reduce growth cells contacting and suppress.Used as preferable Tissue Engineering Biomaterials, collagen is applied in cosmetics and hemostasis class medicine equipment always, with vast potential for future development.
In the patent application of collagen eye drops（Public Jian CN1927391A) in, its collagen applied is not known effective component group, and when collagen is prepared, technological parameter is indefinite, result in obtained active component indefinite；Bian is digested with pepsin or papain in the patent application, because the enzymolysis specificity of pepsin is limited, it can not digest the proline peptide bond in collagen, i other words pepsin cannot be by collagen enzymolysis plastic original albumen, therefore collagen described in patent application collagen not on practical significance（Relative molecular weight is not higher than 100kD), therefore the patent application does not have feasibility；In the patent application of composite collagen eye drops（Publication number CN1927392A) in add chemical drug antibiotic and come and collagen use in conjunction, but it is only limitted to the application in terms of chemical drugs, do not have reproducibility for the Chinese medicine of complicated component, and the patent is equally not known the effective component group of collagen, has obscured the concept of collagen and collagen.It can be seen that prior art does not have the real technical problem for solving collagen or collagen in ophthalmic remedy, situation about especially collagen or collagen are combined with Chinese medicine.
In view of middle extensive use of the Chinese medicine in eye-drops preparations, now in the urgent need to collagen and Effective Component of Chinese Medicine are combined into application, simultaneously, it is necessary to by control the methods such as its molecular weight ranges come the effective part group of clear and definite collagen, with ensure apply when security and validity.
The content of the invention
The first object of the present invention is to provide a kind of Chinese medicine composition for treating glaucoma, and the Chinese medicine composition is by collagen and stimulates the menstrual flow, go screen, step-down class Chinese medicine to constitute.
Second purpose is to provide application of the Chinese medicine composition in terms of various congenital glaucomas, primary glaucoma, secondary glaucoma and mixed glaucoma is treated.
Specifically：
The invention provides a kind of Chinese medicine composition for treating glaucoma, the bulk drug of the Chinese medicine composition active ingredient commonly uses at least one stimulated the menstrual flow, go in screen, step-down class Chinese medicine for collagen and following ophthalmology：Ergcibe obtusifolia, betel nut, ginkgo leaf, the red sage root, erigeron breviscapus, the root of fangji, the root of kudzu vine, Pachyrhizua angulatus, antelope's horn, calculus bovis factitius, the shell of seaear, Cassia occidentalis, Fructus Corni, selfheal, myrobalan, the wind-weed, radix bupleuri, the fruit of Chinese wolfberry, chrysanthemum.
It is the medicinal herbs most in use of all kinds of glaucomas of clinical treatment to be stimulated the menstrual flow selected by above-mentioned, go screen, step-down class Chinese medicine, with solid clinical practice basis.In addition, above-mentioned ingredients is in pharmaceutical procedures of the invention are prepared, can be used as medicine with former powder, it is also possible to select suitable method to be extracted according to the exclusive physicochemical property of active ingredient, refine, obtain corresponding extract and fed intake.
Collagen and the weight proportion of traditional Chinese medicine ingredients are 1 in Chinese medicine composition active ingredient of the present invention: 0.1〜1:20, preferred weight proportion is 1: 0.3〜1: 10.Wherein Effective Component of Chinese Medicine mean above-mentioned clearing heat and diminishing inflammation Chinese medicine it is extracted after obtained by Chinese medical extract and（Or）Medicinal material original powder, refers to the two solid content weight ratio in final products with the part by weight of collagen.
And, collagen can be that collagen or collagen individually feed intake described in present invention gained Chinese medicine composition, can also be the mixed material feeding of collagen and collagen, essentially consist in that the two property is similar, and simply there is some difference for molecular weight.Collagen refers to the spirality fiber shape protein twisted into by three peptide chains, it is to constitute the important protein of animal connective tissue, its main simple hydrolysis from the raw materials such as pigskin, ox-hide, ox heel string, pig heel string, pig bone, ox bone is obtained, the list such as general Bian pepsins, papain or cradin enzyme enzymolysis during enzymolysis, more at low temperature（Less than 10 °C）Carry out, prevent albuminous degeneration, the right-handed helix main structure body of uniqueness is not destroyed, only cut off non-Collagen tail peptide position, its relative molecular weight is 250 300kD, with complete triple-helix structure；Collagen further hydrolyzes to obtain gelatin, and its relative molecular weight is 100 200kD, and oneself is destroyed for triple-helix structure；Collagen is the further enzymolysis product of gelatin, and, in below 100kD, wherein the overwhelming majority exists in the form of collagen oligopeptide, relative molecular weight is in below 40kD for its relative molecular weight.Collagen can also directly be digested from the raw materials such as gelatin, donkey-hide gelatin, new donkey-hide gelatin and obtained.The relative molecular weight of collagen and gelatin is big, poorly water-soluble, viscosity is high, and mechanical strength is big, ancillary drug good moldability, the carrier of eye-drops preparations medicine is also used as, medicine is gradually discharged in conjunctival sac, so as to make intraocular drug reach higher concentration in a short time, and kept for the long period, the general toxicity of medicine is reduced, and in the presence of clostridiopetidase A, oligopeptides can be digested into or amino acid is participated in tissue growth；And the relative molecular weight of collagen is smaller, it has preferable repairing corneal disturbance in ophthalmic applications, promotes wound healing, increase eye nutrition, alleviate the multiple efficacies such as visual fatigue.
Collagen used of the invention is obtained through enzymatic isolation method by gelatin, donkey-hide gelatin, new donkey-hide gelatin, pigskin, ox-hide, pig bone, ox bone, pig heel string or ox heel string, and its relative molecular weight is not higher than 100kD.
Collagen main preparation methods of the invention used are：Collage raw material is taken, clear water or salting liquid are cleaned, and remove the impurity such as fatty, residual meat, acid adding or alkali adjust proper pH value, low temperature（0 10 °C) digest 24 72 hours, centrifugation, supernatant is taken, regulation is appropriatePH values, add required protease fully to be digested, and take supernatant, plus neutral salt is saltoutd, removal of impurities of dialysing, and is further purified, and is obtained final product.
More specifically, the primary raw material of collagen used of the invention derives from gelatin, donkey-hide gelatin, new donkey-hide gelatin, pigskin, ox-hide, pig bone, ox bone, any one or a few with of pig heel string or ox, it is obtained by thoroughly enzymolysis, its relative molecular weight is preferably below 10kD, more preferably 5kD, the enzyme solution can be pepsin, trypsase, pancreatin, neutral proteinase, alkali protease, bromelain, the single enzyme enzymolysis of any one in ficin or papain, it can also be pepsin, trypsase, pancreatin, neutral proteinase, alkali protease, bromelain, the combination enzymolysis of any several enzymes in ficin or papain, can also be the bionic enzyme solution for copying human consumption's absorption process completely（That is Bian first simulation human stomach's digestion process and the pepsin enzymatic isolation method of physical and chemical parameter, are then simulated the pancreas that human body intestinal canal digests and assimilates process and physical and chemical parameter（Albumen）Enzyme enzymatic isolation method, so as to the low molecule oligopeptides material for obtaining being available for human body directly to absorb）.Collagen used of the invention is obtained through enzymolysis by pigskin, ox-hide, pig bone, ox bone, pig heel string or ox heel string, and its relative molecular weight is 250 300kD.
Collagen used of the invention is mainly obtained using following preparation method：
Collage raw material is taken, clear water or salting liquid are cleaned, and remove the impurity such as fatty, residual meat, acid adding or alkali adjust proper pH value, low temperature（01 (TC) are digested 24 72 hours, centrifugation, take supernatant, plus neutral salt is saltoutd, removal of impurities of dialysing, and are further purified, and are obtained final product.
More precisely, the primary raw material of collagen used of the invention derives from pigskin, ox-hide, pig bone, ox bone, any one or a few in pig heel string or ox heel string, it is obtained by appropriate enzymatic isolation method, its relative molecular weight is 250 300kD, the enzyme solution can be pepsin, trypsase, pancreatin, neutral proteinase, alkali protease, bromelain, the single enzyme enzymolysis of any one in ficin or papain, it can also be pepsin, trypsase, pancreatin, neutral proteinase, alkali protease, bromelain, the combination enzymolysis of any several enzymes in ficin or papain.
In the preparation technology of above-mentioned collagen or collagen, acid used is any one or a few in tartaric acid, malic acid, acetic acid, citric acid, glycine or hydrochloric acid, and alkali used is any one or a few in ammoniacal liquor, NaOH, potassium hydroxide, sodium carbonate or sodium acid carbonate.
In the preparation technology of above-mentioned collagen or collagen, salt used of saltouing can be any one or a few in ammonium sulfate, magnesium sulfate, sodium sulphate, sodium chloride or sodium phosphate.
The main Bian of Chinese medicine composition of the present invention is obtained with following preparation method：
A, selected Chinese medicine is taken, crushed, Bian water extractions/alcohol extracting/elder generation's alcohol extracting water extraction/elder generation's water extraction alcohol extracting/stay the methods such as powder that drug extract is obtained again again；
B, take obtained collagen solution or fine powder, add said medicine extract, appropriate ophthalmology pharmaceutic adjuvant is added, formulation needed for being obtained according to pharmacy routine techniques, such as eye drops, gel for eye use, instant gel for eye, eye ointment, eye patch, ophthalmically acceptable powder and film eye-drops preparations.
People's cornea is mainly what is be made up of collagen, by collagen with stimulate the menstrual flow, go screen, step-down class Chinese medicine to use cooperatively, collagen on the one hand can be made directly to play tissue repair and to be acted on, improve the symptom such as conjunctival hyperemia；On the other hand, stimulate the menstrual flow, go screen, fundamentally the symptom such as, bloodshot eyes high to intraocular pressure is treated for promoting blood circulation, the antihypertensive effect of step-down class Chinese medicine.Both use cooperatively, and can play more preferable therapeutic effect.
In addition, to improve preparation curative effect, preferably play the combination of Chinese medicine and collagen, Chinese medicine composition of the present invention can also add except it is described stimulate the menstrual flow, go screen, step-down class Chinese medicine in addition to medicine, as added hirudo extract, Eupolyphaga seu steleophaga extract with promoting blood circulation effect, the Berberine hydrochloride with bactericidal action is added, acted on increase stickiness, extension drug release time plus Sodium Hyaluronate is added, addition has honey of hypertonic effect etc..
Chinese medicine composition in the present invention is mainly used in the application in the various glaucoma medicines for the treatment of are prepared, and is the application in the medicines such as the various congenital glaucomas for the treatment of, primary glaucoma, secondary glaucoma and mixed glaucoma are prepared more precisely.
Beneficial effect
Further to verify the therapeutic action of product of the present invention, inventor has carried out following experiment.
Experiment one, influence of the eye drops of the present invention to rabbit experiment Bulbi hypertonia
Test material
Schiotz intraocular pressure juice, Suzhou Medical Instruments Factory's production.
1% methylcellulose：Take lg methylcellulose（Ahua Pharmaceutical Co., Ltd., Liaocheng, Shandong produces）In the injection ringer's solution 30ml that addition is boiled, injection ringer's solution 70ml is added after cooling, autoclave sterilization sterilizing is standby.
Erycibes eye drops：Ergcibe obtusifolia 2kg is taken, coarse crushing, plus 8 times of amounts decocting is boiled twice, each 2h, filtration, merging filtrate, it is concentrated under reduced pressure into right amount, plus ethanol makes alcohol content up to 75%, stands overnight, take supernatant and ethanol is recovered under reduced pressure to without alcohol taste, remaining aqueous add the ethanol to make alcohol content up to 85% again, stand overnight, and take supernatant and ethanol is recovered under reduced pressure to without alcohol taste, remaining aqueous filtration, it is standby；Water for injection 800ml is taken, boric acid 12g, borax 0.6g, ethylparaben 0.6g is added, 70 °C are heated to, stirred to clarify, filtered, stirring is lower to add above-mentioned ergcibe obtusifolia extract solution, adds collagen extract solution 50ml (containing collagen 5g) and collagen extraction liquid 20ml (containing collagen 2g), stir, inject water to 1kg, cross miillpore filter, it is aseptic subpackaged, obtain final product.（Note：Collagen used is obtained for donkey-hide gelatin by pepsin and pancreatin bionic enzymatic, by the milipore filter ultrafiltration of 10kD；Collagen is with pigskin and ox-hide as raw material, plus second acid for adjusting pH is 2.0, is obtained through pepsin enzymolysis, and relative molecular weight is in 250 285kD)
Experimental animal
New zealand rabbit, male and female dual-purpose, 2.2 2.5kg, totally 50, purchased from Laboratory Animal Science portion of Peking University.
Test method
Glaucoma model is set up：18 rabbit are randomly divided into three groups, respectively every group 6, blank control group, model control group and Erycibes eye drops group.Repeatedly injection rabbit anterior chamber sets up Ocular hypertensive model on a small quantity to take 1% methylcellulose of model control group and Erycibes eye drops group, and single cage is raised respectively.
Medication：Blank control group, model control group give water for injection, and Erycibes eye drops group gives Erycibes eye drops.4 times/d of administration, 12 drops/time, with 12h Jian beginning medications after modeling, 9d, is observed daily by a definite date.
Experiment two：Eye drops vitro release of the present invention investigates test material
Erycibes eye drops（Plus collagen）：With experiment one；
Erycibes eye drops（Commonly)：Ergcibe obtusifolia 2kg is taken, coarse crushing, plus 8 times of amounts decocting is boiled twice, each 2h, filtration, merging filtrate, it is concentrated under reduced pressure into right amount, plus ethanol makes alcohol content up to 75%, stands overnight, take supernatant and ethanol is recovered under reduced pressure to without alcohol taste, remaining aqueous add the ethanol to make alcohol content up to 85% again, stand overnight, and take supernatant and ethanol is recovered under reduced pressure to without alcohol taste, remaining aqueous filtration, it is standby：Water for injection 800ml is taken, boric acid 12g, borax 0.6g, ethylparaben 0.6g is added, 70 °C are heated to, stirred to clarify, filtration, stirring is lower to add above-mentioned ergcibe obtusifolia extract solution, stirs, and injects water to 1kg, miillpore filter is crossed, it is aseptic subpackaged, obtain final product；
Shimadzu LC-2010A high performance liquid chromatographs, Shimadzu CLASS-VP work stations；
Isotonic phosphate buffer liquid（Contain NaH in 1000ml solution2P04 1.60g, Na2HP047. 40) 58g, the 32g of NaCl 4., adjust pH to 7.
Test method
Take Erycibes eye drops（Plus glue Hao albumen）And Erycibes eye drops（Commonly）Each 10ml, is respectively placed in bag filter, and bag two is tightened with nylon wire（Bubble is removed in bag), it is fixed in 250ml beakers, dissolution medium is isotonic phosphate buffer liquid 100ml, along apart from liquid level lcm on bag, beaker is placed on magnetic stirrer, and stirrer is about 2. 5cm, temperature control（34 ± 1) °C, 5ml is sampled at regular intervals, while adding the fresh phosphate buffer of same volume.
The content for taking ergcibe obtusifolia in each sample is determined respectively, is represented with peak area.Cumulative diffusion drug release amount is calculated as follows:Ci=f (Ai), Qn=100Cn+5E CA(Q1=100Ci i, n=l, 2,3 ...) (G is drug concentration, and to measure peak area, Q is drug accumulation burst size to A, and i, ri is respectively sampling number of times.）Result of the test
Data according to collection draw Erycibes eye drops（Plus collagen）And Erycibes eye drops（Commonly）In-vitro release curves, and the cumulative release curve is carried out into release equation model, as a result it has first-order release rule, and regression equation has good correlation.One-level drug release fit equation be：Log (Y.-Y)=mono- KrXt/2.303+M.The Erycibes eye drops that Chinese medicine composition of the present invention is made（Plus collagen）Release equation be：Log (Y«~Y) =-0.1732x+2. 1386, coefficient correlation is 0.9973.
Result shows, Erycibes eye drops（Commonly）In vitro release it is very fast, drug release reaches 77% during lh, afterwards into plateau；And Erycibes eye drops（Plus collagen）In 3h, drug release reaches 83%, and drug release rate is gentle, with preferable slow release characteristic.It can be seen that, Erycibes eye drops（Plus collagen）With preferable slow release characteristic, the bioavilability that preparation is improved by Chinese medicine composition of the invention in eye has feasibility.
Specific embodiment
The present invention is further illustrated below by way of specific embodiment, but following examples are merely to illustrate the present invention and the present invention are not limited.
Embodiment one：
Prescription：Ergcibe obtusifolia 10kg collagen extract solutions 500ml (containing collagen 25g) preparation method：Caulis Erycibes are taken, coarse crushing, plus 8 times of amounts decocting is boiled twice, each 2h, filtration, merging filtrate, it is concentrated under reduced pressure into right amount, plus ethanol makes alcohol content up to 75%, stands overnight, take supernatant and ethanol is recovered under reduced pressure to without alcohol taste, remaining aqueous add the ethanol to make alcohol content up to 85% again, stand overnight, and take supernatant and ethanol is recovered under reduced pressure to without alcohol taste, remaining aqueous filtration, it is standby；Water for injection 4000ml is taken, boric acid, borax, ethylparaben is added, 70 °C are heated to, stirred to clarify, filtration, stirring is lower to add above-mentioned ergcibe obtusifolia extract solution, adds collagen extract solution, stirs, 5000g is injected water to, miillpore filter is crossed, it is aseptic subpackaged, obtain final product.（Note：Collagen used is that donkey-hide gelatin is obtained by pepsin and trypsase bionic enzymatic, then by the milipore filter ultrafiltration of 3kD）.
Embodiment two：
Prescription：Betel nut 3000g Sodium Hyaluronate lg collagen extract solutions 100ml (containing collagen 5g) preparation method：Take betel nut medicinal material, coarse crushing is filtered extractions with 1% salt acid dip and Seepage, collects 8 times of amount percolates, is concentrated into right amount, pH to 10 is adjusted with ammoniacal liquor, is extracted five times with chloroform, merge chloroform liquid, reclaim chloroform, plus ethanol stirring and dissolving, ethanol is reclaimed, remaining aqueous filtration is standby；Water for injection 1600ml is taken, gellan gum is added, equal Uniform is stirred, put in boiling water bath, stir to clarify, add boric acid, borax, ethylparaben, 70 °C are heated to, are stirred to clarify, filtered, stirring is lower to add above-mentioned aqueous areca nut extract, collagen extract solution is added, 2000g is injected water to, Sodium Hyaluronate is added, abundant swollen makes dissolving, crosses miillpore filter（0.22um), it is aseptic subpackaged, obtain final product.（Note：Collagen used is that pig bone and ox bone are digested by alkali protease, then is obtained by the milipore filter ultrafiltration of 5kD）.

Claims (3)

1. a kind of Chinese medicine composition for treating glaucoma, it is characterised in that the bulk drug of the Chinese medicine composition active ingredient is collagen and following any one or more stimulated the menstrual flow, go in screen, step-down class Chinese medicine：Ergcibe obtusifolia, betel nut, ginkgo leaf, the red sage root, erigeron breviscapus, the root of fangji, the root of kudzu vine, Pachyrhizua angulatus, antelope's horn, calculus bovis factitius, the shell of seaear, Cassia occidentalis, Fructus Corni, selfheal, myrobalan, the wind-weed, radix bupleuri, the fruit of Chinese wolfberry, chrysanthemum.
2. Chinese medicine composition according to claim 1, it is characterised in that the ratio of collagen and traditional Chinese medicine ingredients is 1 in the Chinese medicine composition active ingredient: 0. 1〜1: 20.
3. Chinese medicine composition according to claim 2, it is characterised in that the ratio of collagen and traditional Chinese medicine ingredients is 1 in the Chinese medicine composition active ingredient: 0.3〜1: 10.
CN201510966428.6A 2015-12-22 2015-12-22 It is a kind of to treat Chinese medicine composition of glaucoma and application thereof Pending CN106902344A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112336761A (en) * 2020-12-04 2021-02-09 广州陈锦济生物科技有限公司 Anti-radiation eye moistening liquid and preparation method thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112336761A (en) * 2020-12-04 2021-02-09 广州陈锦济生物科技有限公司 Anti-radiation eye moistening liquid and preparation method thereof

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