CN101461834A - Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof - Google Patents
Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof Download PDFInfo
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Abstract
The invention provides a method for preparing cervus and cucumis polypeptide medicine composition oral preparation on one hand. The method comprises: firstly, preparing a deer bone extracting solution; secondly, preparing a melon seed extracting solution; and thirdly, combining the deer bone extracting solution and the melon seed extracting solution, and obtaining the cervus and cucumis polypeptide medicine composition oral preparation. The invention also provides a cervus and cucumis polypeptide medicine composition prepared by the method. Compared with the prior method for preparing the cervus and cucumis polypeptide medicine composition oral preparation, the method has the advantages that the method adjusts the pH value when preparing the deer bone extracting solution and the melon seed extracting solution, and removes impurity proteins in the extracting solution through ultrafiltration by an ultrafiltration membrane, so as to guarantee the quality and the safety of products and improve the stability and the treatment effect of the products.
Description
Technical field
The present invention relates to a kind of cervus and cucumis polypeptide drug composition oral preparation and preparation method thereof, relate in particular to a kind of cervus and cucumis polypeptide drug composition oral preparation, belong to biomedicine field.
Background technology
Contain inorganic elementss such as the bioactive peptide material of multiple bone metabolism and calcium, phosphorus, ferrum in the cervus and cucumis polypeptide pharmaceutical composition, Fructus Melo seed extract and multiple free amino acid etc., its pharmacological action is to regulate bone metabolism and alcium and phosphor metabolization, stimulating osteoblast propagation, promote new bone formation and regulate calcium, phosphorus metabolism, increase bone calcium, phosphorus deposition, prevent osteoporosis, have analgesia, antiinflammatory action; Can obviously reduce the permeability of the local blood capillary of fracture, reduce inflammatory exudation, promote local blood circulation, for osteocyte provides a good blood supply environment.The cervus and cucumis polypeptide pharmaceutical composition can be facilitated the osteocyte growth, promotes intermembranous ossification and chondrify, and is remarkable to curative effect of fracture, and multiple bone injury disease is had significant curative effect.
Domestic patent of invention about the cervus and cucumis polypeptide pharmaceutical composition have 200510108157.7 hereinafter referred to as documents 1,200410013602.7 hereinafter referred to as documents 2 and 02125357.9 hereinafter referred to as documents 3.The preparation method that documents 1 adopts is that Os Cervi and the hot pressing extraction respectively of Fructus Melo seed, centrifugal, ultrafiltration are prepared from, in this extracting method, both do not regulate the Os Cervi extracting liquid pH value, do not regulated the pH value of Fructus Melo seed extracting solution yet, so do not comprised the proteic removal method of impurity in this method.The preparation method that documents 2 adopts is that Os Cervi is removed impurity albumen, centrifugal, ultrafiltration through hot pressing extraction, soda acid, the Fructus Melo seed through hot pressing extract, centrifugal, ultrafiltration is prepared from, this invention is only removed the impurity albumen that contains in the Os Cervi, Fructus Melo seed extracting solution is not carried out the adjusting of pH value, therefore do not remove the impurity albumen of Fructus Melo seed extracting solution.The preparation method that documents 3 adopts is that Os Cervi is carried out heating extraction, and hydrochloric acid is regulated the pH value of extracting solution, carry out again freezing static, heated and boiled acid extraction liquid, reuse alkali is regulated filtering supernatant, the freezing static Os Cervi extracting solution that obtains; The preparation method of this invention Fructus Melo seed extracting solution is identical with the preparation method of Os Cervi extracting solution, and Os Cervi extracting solution and the mixing of Fructus Melo seed extracting solution that obtains concentrated, and regulates the pH value of concentrated solution, then carries out ultra-filtration filters, makes the cervus and cucumis polypeptide pharmaceutical composition.When the present application people found to adopt the method for above-mentioned documents 1 and documents 2 to prepare the cervus and cucumis polypeptide pharmaceutical composition, because impurity protein content height wherein, the storage life of product was affected; When the method for employing documents 3 prepares the Os Cervi polypeptide pharmaceutical composition, owing to both needed freezing preservation in operation, need heated and boiled again, operational approach is too complicated, the control of pharmaceutical composition difficult quality.
At present, the preparation of cervus and cucumis polypeptide pharmaceutical composition has been widely used in clinical, but find in practice: along with the prolongation of cervus and cucumis polypeptide drug combination preparation storage time, the part finished product has precipitation and separates out, thereby has caused visible foreign matters, particulate matter not to meet the regulation of Chinese Pharmacopoeia.This not only influences the quality of medicine, and has brought titanic peril to clinical practice.The reason that this problem takes place is: the impurity albumen that all contains a large amount of no drug activities in Os Cervi and the Fructus Melo seed, if impurity albumen is not removed the curative effect that not only can influence medicine, and can influence the quality of medicine, thereby can bring titanic peril to clinical practice.Above-mentioned documents 1 and documents 2 are all less than fully impurity albumen being removed.In order to address this problem, research worker of the present invention is through repeatedly verification experimental verification, find out and a kind ofly can guarantee end product quality, the easy again operational approach of controlling, can guarantee simultaneously the cervus and cucumis polypeptide preparation of drug combination method of stability of formulation, simultaneously invented the cervus and cucumis polypeptide drug composition oral preparation on this basis, thereby a kind of quality is more stable, safer, more effective, the cervus and cucumis polypeptide drug composition oral preparation of taking convenience for extensive patients provides.
Summary of the invention
One aspect of the present invention provides a kind of cervus and cucumis polypeptide drug composition oral preparation, and it has, and long shelf-life, quality stability are good, safe, effective, the advantage of taking convenience.
The present invention provides a kind of described cervus and cucumis polypeptide preparation of drug combination method on the other hand.
One aspect of the present invention provides a kind of preparation method of cervus and cucumis polypeptide drug composition oral preparation, and this method may further comprise the steps:
1. the preparation of Os Cervi extracting solution:
A. at first Os Cervi is carried out pretreatment;
B. pretreated Os Cervi is pulverized, then added the water for injection of 3-5 times of Os Cervi weight, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate;
C. pH value of filtrate is adjusted to 4.5-6.0;
D. the filtrate that will regulate behind the pH value was at room temperature placed 1-4 hour, filtered, and collected filtrate, again filtrate was carried out centrifugalize, collected supernatant I, and the pH value of regulating supernatant I is 10.0-11.0;
E. the supernatant I room temperature that will regulate behind the pH value was placed 1-4 hour, filtered, and collected filtrate, again filtrate was carried out centrifugalize, collected supernatant II, and the pH value of regulating supernatant II be a neutrality;
F. the neutral supernatant II that step e is obtained is 100,000,10,000 and 5000 daltonian ultrafiltration membrance filters through molecular weight successively, collects ultrafiltrate, obtains described Os Cervi extracting solution;
2. the preparation of Fructus Melo seed extracting solution:
G. at first the Fructus Melo seed is carried out pretreatment;
H. pretreated Fructus Melo seed is pulverized, then added the water for injection of 3-5 times of Fructus Melo seed weight, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate;
I. repeat above-mentioned steps c-f, obtain described Fructus Melo seed extracting solution;
3. the preparation of cervus and cucumis polypeptide drug composition oral preparation:
J. described Os Cervi extracting solution and the described Fructus Melo seed extracting solution weight ratio with 1-2:1 is merged, also in merging back Os Cervi extracting solution and described Fructus Melo seed extracting solution, add pharmaceutically acceptable correctives, the adjusting pH value is 4.5-7.5, use micro-pore-film filtration, collect filtrate, obtain described cervus and cucumis polypeptide drug composition oral preparation.
Preferably, between described step b and c, also comprise step k, described step k adds filtering residue weight 3-5 water for injection doubly for filtering to step b in the filtering residue that obtains, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate I, and the filtrate that filtrate I and step b obtain is merged.
Preferably, in described step j, described microporous membrane is that the aperture is the microporous membrane of 0.22-0.45 μ m.
More preferably, described microporous membrane is that the aperture is the microporous membrane of 0.22 μ m.
Preferably, in described step f, also ultrafiltrate is used the microporous filter membrane filtration.
Preferably, in the step g among pretreated Fructus Melo seed and the step a weight ratio of pretreated Os Cervi be 0.25-4:1.
Preferably, in step a described Os Cervi being carried out pretreatment is at first to remove the connective tissue on the Os Cervi surface of fresh and healthy, then clean Os Cervi; In described step g, the Fructus Melo seed is carried out pretreatment for sophisticated Fructus Melo seed is cleaned.
Preferably, described pharmaceutically acceptable correctives is one or more in sucrose, simple syrup, Mel, rob, sweetleaf centautin, cyclamate, protein sugar, saccharin sodium, sorbitol and the maltose syrup.
Preferably, with hydrochloric acid pH value of filtrate is adjusted to 4.5-6.0 among the step c, the pH value with NaOH adjusting supernatant in the steps d is 10.0-11.0.
Preferably, described oral formulations is an oral administration solution.
Preferably, wherein said Os Cervi is the Os Cervi of Cervus nippon Temminck.
Further aspect of the present invention also provides a kind of preparation method of cervus and cucumis polypeptide drug composition oral preparation, and this method is made up of following steps:
1. the preparation of Os Cervi extracting solution:
A. at first Os Cervi is carried out pretreatment;
B. pretreated Os Cervi is pulverized, then added the water for injection of 3-5 times of Os Cervi weight, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate;
C. pH value of filtrate is adjusted to 4.5-6.0;
D. the filtrate that will regulate behind the pH value was at room temperature placed 1-4 hour, filtered, and collected filtrate, again filtrate was carried out centrifugalize, collected supernatant I, and the pH value of regulating supernatant I is 10.0-11.0;
E. the supernatant I room temperature that will regulate behind the pH value was placed 1-4 hour, filtered, and collected filtrate, again filtrate was carried out centrifugalize, collected supernatant II, and the pH value of regulating supernatant II be a neutrality;
F. the neutral supernatant II that step e is obtained is 100,000,10,000 and 5000 daltonian ultrafiltration membrance filters through molecular weight successively, collects ultrafiltrate, obtains described Os Cervi extracting solution;
2. the preparation of Fructus Melo seed extracting solution:
G. at first the Fructus Melo seed is carried out pretreatment;
H. pretreated Fructus Melo seed is pulverized, then added the water for injection of 3-5 times of Fructus Melo seed weight, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate;
I. repeat above-mentioned steps c-f, obtain described Fructus Melo seed extracting solution;
3. the preparation of cervus and cucumis polypeptide drug composition oral preparation:
J. described Os Cervi extracting solution and the described Fructus Melo seed extracting solution weight ratio with 1-2:1 is merged, also in merging back Os Cervi extracting solution and described Fructus Melo seed extracting solution, add pharmaceutically acceptable correctives, the adjusting pH value is 4.5-7.5, use micro-pore-film filtration, collect filtrate, obtain described cervus and cucumis polypeptide drug composition oral preparation.
Preferably, between described step b and c, also comprise step k, described step k adds filtering residue weight 3-5 water for injection doubly for filtering to step b in the filtering residue that obtains, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate I, and the filtrate that filtrate I and step b obtain is merged.
Preferably, in described step j, described microporous membrane is that the aperture is the microporous membrane of 0.22-0.45 μ m.
More preferably, described microporous membrane is that the aperture is the microporous membrane of 0.22 μ m.
Preferably, in described step f, also ultrafiltrate is used the microporous filter membrane filtration.
Preferably, in the step g among pretreated Fructus Melo seed and the step a weight ratio of pretreated Os Cervi be 0.25-4:1.
Preferably, in step a described Os Cervi being carried out pretreatment is at first to remove the connective tissue on the Os Cervi surface of fresh and healthy, then clean Os Cervi; In described step g, the Fructus Melo seed is carried out pretreatment for sophisticated Fructus Melo seed is cleaned.
Preferably, described pharmaceutically acceptable correctives is one or more in sucrose, simple syrup, Mel, rob, sweetleaf centautin, cyclamate, protein sugar, saccharin sodium, sorbitol and the maltose syrup.
Preferably, with hydrochloric acid pH value of filtrate is adjusted to 4.5-6.0 among the step c, the pH value with NaOH adjusting supernatant in the steps d is 10.0-11.0.
Preferably, described oral formulations is an oral solution.
Preferably, wherein said Os Cervi is the Os Cervi of Cervus nippon Temminck.
Further aspect of the present invention provides a kind of cervus and cucumis polypeptide drug composition oral preparation that is prepared from by described method.
The invention has the advantages that: 1. all carried out regulating the operation of pH value in the inventive method when preparation Os Cervi extracting solution and Fructus Melo seed extracting solution, the present invention simultaneously is controlled at pH value in the narrow relatively scope when regulating extracting liquid pH value.This is because the present application people is surprised to find, so the purpose of operation is in the operation of regulating pH value, remove the impurity albumen in the extracting solution, keep the useful albumen in the extracting solution simultaneously, under the prerequisite that keeps cervus and cucumis polypeptide pharmaceutical composition medicinal effects, this pharmaceutical composition storage life is prolonged, pH value is controlled in this scope simultaneously, saved and follow-uply in the prior art passed through freezing static and heated and boiled and remove sedimentary operation, both guaranteed product stability, simplified preparation technology again, preparation technology of the present invention in addition is simple and be convenient to control.Remove the impurity albumen in the extracting solution by this operation, thereby guaranteed the quality of product, increased the stability of product, guaranteed security of products.
2. the present invention is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration with molecular weight respectively with Os Cervi extracting solution and Fructus Melo seed extracting solution successively, collected molecular weight less than 5000 daltonian ultrafiltrates, it is better that the ultrafiltrate that has proved this molecular weight ranges through pharmacodynamics test and the solution of other molecular weight ranges are compared medical effect, and the stability of the pharmaceutical composition that is prepared from simultaneously also is better than the solution of other molecular weight ranges.
3. oral formulations preferred oral solution of the present invention is a liquid formulation still, has effect rapidly, eutherapeutic characteristics.Because of unit dose package, so carry, taking convenience.
4. divided dose of the present invention is accurate, and dose is little, and the delicious easy patient of being accepts.The present invention is that aseptic condition is sealed in the oral liquid standard jar, and it is long to have a storage period, steady quality, not perishable characteristics.
The specific embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage of the present invention and characteristics will be more clear along with description.But these embodiment only are exemplary, scope of the present invention are not constituted any restriction.It will be understood by those skilled in the art that and down can make amendment or replace without departing from the spirit and scope of the present invention, but these modifications and replacing all fall within the scope of protection of the present invention the details of technical solution of the present invention and form.
Embodiment 1
(1) preparation of Os Cervi extracting solution: get fresh and healthy Os Cervi 20kg, remove the connective tissue on surface, clean, be broken into fritter, add the water for injection of 3 times of weight, i.e. 60kg extracted 3 hours down in 121 ℃, 0.1MPa pressure, filtered, and collected filtrate.To extract residual residue with quadrat method, filter, and collect filtrate I, merge Os Cervi filtrate and filtrate I.Add the 3mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 4.5, at room temperature, placed 1 hour, filter, collect filtrate, again filtrate is carried out centrifugalize, collect supernatant I.Upwards add the 3mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 10.0, at room temperature, placed 1 hour, filter, collect filtrate, centrifugal, collect supernatant II.The pH value of regulating supernatant II is to neutral, and promptly 7.0, neutral supernatant II is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively successively, collects ultrafiltrate, makes the Os Cervi extracting solution.
(2) preparation of Fructus Melo seed extracting solution: get sophisticated Fructus Melo seed 80kg, clean, be ground into powder, add the water for injection of 3 times of weight, i.e. 240kg extracted 3 hours down in 121 ℃, 0.1MPa pressure, filtered, and collected filtrate.With quadrat method residual residue hot pressing is extracted, filter, collect filtrate I, merge Fructus Melo seed filtrate and filtrate I.Add the 3mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 4.5, at room temperature, placed 1 hour, filter, collect filtrate, centrifugal, collect supernatant I.Upwards add the 3mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 10.0, placed 1 hour, filter, collect filtrate, centrifugal, collect supernatant II.The pH value of regulating supernatant II is to neutral, and promptly 7.0, neutral solution is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively successively, collects ultrafiltrate, makes Fructus Melo seed extracting solution.
(3) weight ratio according to 1:1 merges Os Cervi extracting solution and Fructus Melo seed extracting solution, adds suitable amount of sucrose or simple syrup, and the pH value of regulator solution is 4.5, with the filtering with microporous membrane of 0.22 μ m, collects filtrate, makes cervus and cucumis polypeptide drug composition oral solution.
Embodiment 2
(1) preparation of Os Cervi extracting solution: get fresh and healthy Os Cervi 50kg, remove the connective tissue on surface, clean, be broken into fritter, add the water for injection of 4 times of weight, i.e. 200kg extracted 4 hours down in 121 ℃, 0.11MPa pressure, filtered, and collected Os Cervi filtrate.Extract residual residue with quadrat method, filter, collect filtrate I, merge Os Cervi filtrate and filtrate I.Add the 4mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 5.0, at room temperature, placed 3 hours, filter, collect filtrate, again filtrate is carried out centrifugalize, collect supernatant I.Upwards add the 4mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 11.0, at room temperature, placed 3 hours, filter, collect filtrate, centrifugal, collect supernatant II.Regulate the pH value to 7.0 of supernatant II, neutral supernatant II is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively successively, collects ultrafiltrate.Filtrate is collected filtrate with the filtering with microporous membrane of 0.22 μ m, makes the Os Cervi extracting solution.
(2) preparation of Fructus Melo seed extracting solution: get sophisticated Fructus Melo seed 25kg, clean, be ground into the water for injection that powder adds 4 times of weight, i.e. 100kg, 0.11MPa extracted 4 hours under 121 ℃ of pressure, filtered, and collected Fructus Melo seed filtrate.With quadrat method residual residue hot pressing is extracted, filter, collect filtrate I, merge Fructus Melo seed filtrate and filtrate I.Add the 4mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 5.0, at room temperature, placed 3 hours, filter, collect filtrate, centrifugal, collect supernatant I.Upwards add the 4mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 11.0, at room temperature, placed 3 hours, filter, collect filtrate, centrifugal, collect supernatant II.Regulate the pH value to 7.0 of supernatant II, neutral supernatant is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively successively, collects ultrafiltrate.Filtrate is collected filtrate with the filtering with microporous membrane of 0.22 μ m, makes Fructus Melo seed extracting solution.
(3) merge Os Cervi extracting solution and Fructus Melo seed extracting solution according to the 2:1 ratio, add suitable amount of sucrose and saccharin sodium, the pH value of regulator solution is 6.0, filtering with microporous membrane with 0.22 μ m, collect filtrate, preparation method according to the oral liquid routine is prepared, and makes cervus and cucumis polypeptide drug composition oral solution.
Embodiment 3
(1) preparation of Os Cervi extracting solution: get fresh and healthy Os Cervi 100kg, remove the connective tissue on surface, clean, be broken into fritter, add the water for injection 500kg of 5 times of weight, extracted 5 hours down, filter, collect Os Cervi filtrate in 121 ℃, 0.11MPa pressure.With quadrat method residual residue hot pressing is extracted, filter, collect filtrate I, merging filtrate I and Os Cervi filtrate.Add the 5mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 6.0, room temperature was placed 4 hours, filtered, and collected filtrate, again filtrate was carried out centrifugalize, collected supernatant I.Upwards add the 5mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 11.0, room temperature was placed 4 hours, filtered, and collected filtrate, and is centrifugal, collects supernatant II.Regulate the pH value to 7.0 of supernatant II, neutral supernatant II is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively, collects ultrafiltrate.Filtrate is collected filtrate with the filtering with microporous membrane of 0.22 μ m, makes the Os Cervi extracting solution.
(2) preparation of Fructus Melo seed extracting solution: get sophisticated Fructus Melo seed 25kg, clean, be ground into powder, add the water for injection of 5 times of weight, i.e. 125kg extracted 5 hours down in 121 ℃, 0.11MPa pressure, filtered, and collected Fructus Melo seed filtrate.With quadrat method residual residue hot pressing is extracted, filter, collect filtrate I, merge Fructus Melo seed filtrate and filtrate I.Add the 5mol/L hydrochloric acid solution in the solution after merging and regulate pH value to 6.0, room temperature was placed 4 hours, filtered, and collected filtrate, and is centrifugal, collects supernatant I.Upwards add the 5mol/L sodium hydroxide solution in the clear liquid I and regulate pH value to 11.0, placed 4 hours, filter, collect filtrate, centrifugal, collect supernatant II.Regulate the pH value to 7.0 of supernatant II, neutral solution is 100,000,10,000,5000 daltonian ultrafilter membrane ultrafiltration through molecular weight respectively, collects ultrafiltrate.Filtrate is collected filtrate with the filtering with microporous membrane of 0.22 μ m, makes Fructus Melo seed extracting solution.
(3) merge Os Cervi extracting solution and Fructus Melo seed extracting solution according to the 4:1 ratio, add an amount of sweetleaf centautin or sorbitol, the pH value of regulator solution is 7.5, filtering with microporous membrane with 0.22 μ m, collect filtrate, preparation method according to the routine of oral liquid is prepared, and makes cervus and cucumis polypeptide drug composition oral solution.
The test example
Stability test:
In order to examine or check the quality stability of the prepared cervus and cucumis polypeptide drug composition oral preparation of the inventive method, sample is placed by the long term test condition, 25 ℃ of temperature, according to the requirement of two appendix related checks of Chinese Pharmacopoeia version in 2005, investigate the visible foreign matters in the sample and the steadiness of particulate matter in 48 months, concrete outcome is as follows:
The sample stability result of the test
The result: sample was placed 48 months according to the accelerated test condition, and the visible foreign matters of sample and particulate matter inspection all meet officinal regulation, prove constant product quality of the present invention, and invented technology can be controlled the quality of product.
Pharmacodynamics test:
In order to examine or check the prepared cervus and cucumis polypeptide drug composition oral preparation of the inventive method whether safely, effectively, carried out following pharmacodynamics test, specifically test as follows:
One, the antiinflammatory action of cervus and cucumis polypeptide drug composition oral preparation research
1. test material
Animal: Wistar rat.
Sample: cervus and cucumis polypeptide oral solution (specification: 2mg/ml)
Aspirin Enteric-coated Tablets
2. test method
The test of rat carrageenan pedal swelling
50 of Wistar rats, be divided into 5 groups at random according to body weight, i.e. model control group (distilled water), the basic, normal, high dosage of cervus and cucumis polypeptide drug composition oral solution (3.5,7,14mg/kg) group, positive control drug Aspirin Enteric-coated Tablets (150mg/kg) group, 10 every group.Freshly prepared 1% carrageenin suspension 0.1ml causes inflammation at the right back sufficient plantar subcutaneous injection of rat, then cervus and cucumis polypeptide drug composition oral solution is pressed 5ml/100g to each group rat oral gavage medicine, every day 1 time, continuous 7 days.Behind the last medicine 1h adopt rat paw volumetric measurement instrument to measure to cause scorching before and cause scorching back 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, the right back sufficient sole of the foot volume of 6h rat, and calculate inhibitory rate of intumesce.
3. result of the test
Result of the test sees the following form 1.
Table 1 cervus and cucumis polypeptide oral solution on Carrageenan cause foot swelling rat inhibitory rate of intumesce influence (%, x ± s, n=10)
Compare * P＜0.05 with model group, * * P＜0.01, * * * P＜0.001
As seen from the above table, compare with model control group, cervus and cucumis polypeptide drug composition oral preparation 3.5mg/kg is causing scorching back 4h, cervus and cucumis polypeptide oral formulations 7mg/kg is causing inflammation back 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, and cervus and cucumis polypeptide oral formulations 14mg/kg 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h after causing inflammation all can significantly suppress the foot swelling (P＜0.05 or P＜0.01) that carrageenin causes.
Two, anxious poison test
Sample: cervus and cucumis polypeptide oral liquid (specification: 2mg/ml)
According to the study of tcm new drug guideline, the cervus and cucumis polypeptide drug composition oral preparation has been carried out the acute toxicity of mouse vein and gastric infusion and observed, because of measuring LD
50So, carry out maximum dosage-feeding and measure.Mouse mainline administration 2 times, accumulated dose is 400mg/kg, is equivalent to 1200 times of clinical human recommended dose (20mg/60kg people/sky), does not find untoward reaction and death; Mouse stomach administration 1 time, dosage is 400mg/kg, is equivalent to 1200 times of clinical human recommended dose (20mg/60kg people/sky), does not find untoward reaction and death.
Conclusion: above result of the test shows, steady quality of the present invention, safe in utilization, effective.
Claims (11)
1. the preparation method of a cervus and cucumis polypeptide drug composition oral preparation, this method may further comprise the steps:
(1) preparation of Os Cervi extracting solution:
A. at first Os Cervi is carried out pretreatment;
B. pretreated Os Cervi is pulverized, then added the water for injection of 3-5 times of Os Cervi weight, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate;
C. pH value of filtrate is adjusted to 4.5-6.0;
D. the filtrate that will regulate behind the pH value was at room temperature placed 1-4 hour, filtered, and collected filtrate, again filtrate was carried out centrifugalize, collected supernatant I, and the pH value of regulating supernatant I is 10.0-11.0;
E. the supernatant I room temperature that will regulate behind the pH value was placed 1-4 hour, filtered, and collected filtrate, again filtrate was carried out centrifugalize, collected supernatant II, and the pH value of regulating supernatant II be a neutrality;
F. the neutral supernatant II that step e is obtained is 100,000,10,000 and 5000 daltonian ultrafiltration membrance filters through molecular weight successively, collects ultrafiltrate, obtains described Os Cervi extracting solution;
(2) preparation of Fructus Melo seed extracting solution:
G. at first the Fructus Melo seed is carried out pretreatment;
H. pretreated Fructus Melo seed is pulverized, then added the water for injection of 3-5 times of Fructus Melo seed weight, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate;
I. repeat above-mentioned steps c-f, obtain described Fructus Melo seed extracting solution;
(3) preparation of cervus and cucumis polypeptide drug composition oral preparation:
J. described Os Cervi extracting solution and the described Fructus Melo seed extracting solution weight ratio with 1-2:1 is merged, also in merging back Os Cervi extracting solution and described Fructus Melo seed extracting solution, add pharmaceutically acceptable correctives, the adjusting pH value is 4.5-7.5, use micro-pore-film filtration, collect filtrate, obtain described cervus and cucumis polypeptide drug composition oral preparation.
2. method according to claim 1, wherein between described step b and c, also comprise step k, described step k adds filtering residue weight 3-5 water for injection doubly for filtering to step b in the filtering residue that obtains, under 120-123 ℃, 0.1-0.11MPa pressure, extracted 3-5 hour, filter, collect filtrate I, and the filtrate that filtrate I and step b obtain is merged.
3. method according to claim 1 and 2, wherein in described step j, described microporous membrane is that the aperture is the microporous membrane of 0.22-0.45 μ m, more preferably, described microporous membrane is that the aperture is the microporous membrane of 0.22 μ m.
4. according to each described method among the claim 1-3, wherein in described step f, also ultrafiltrate is used the microporous filter membrane filtration.
5. according to each described method among the claim 1-4, wherein in the step g among pretreated Fructus Melo seed and the step a weight ratio of pretreated Os Cervi be 0.25-4:1.
6. according to each described method among the claim 1-5, wherein in step a described Os Cervi being carried out pretreatment is at first to remove the connective tissue on the Os Cervi surface of fresh and healthy, then clean Os Cervi; In described step g, the Fructus Melo seed is carried out pretreatment for sophisticated Fructus Melo seed is cleaned.
7. according to each described method among the claim 1-6, wherein said pharmaceutically acceptable correctives is one or more in sucrose, simple syrup, Mel, rob, sweetleaf centautin, cyclamate, protein sugar, saccharin sodium, sorbitol and the maltose syrup.
8. according to each described method among the claim 1-7, wherein the pH value that will merge rear filtrate with hydrochloric acid among the step c is adjusted to 4.5-6.0, and the pH value of regulating supernatant with NaOH in the steps d is 10.0-11.0.
9. according to each described method among the claim 1-8, wherein said oral formulations is an oral administration solution.
10. according to each described method among the claim 1-8, wherein said Os Cervi is the Os Cervi of Cervus nippon Temminck.
11. cervus and cucumis polypeptide drug composition oral preparation that is prepared from by each described method among the claim 1-10.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104127473A (en) * | 2014-07-31 | 2014-11-05 | 哈尔滨圣泰生物制药有限公司 | Pharmaceutical composition for treating bone diseases, injection thereof and preparation methods thereof |
| CN107988302A (en) * | 2018-01-23 | 2018-05-04 | 吉林省吉诺生物工程有限责任公司 | A kind of application of the preparation method and cervus and cucumis polypeptide of cervus and cucumis polypeptide in special medicine purposes food is prepared |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100363019C (en) * | 2005-10-09 | 2008-01-23 | 黑龙江迪龙制药有限公司 | Cervus and cucumis polypeptide injection composition and preparing method |
| CN100382842C (en) * | 2006-05-31 | 2008-04-23 | 哈尔滨吉尔生物科技有限公司 | Orally administered cervus and cucumis polypeptide composition and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104127473A (en) * | 2014-07-31 | 2014-11-05 | 哈尔滨圣泰生物制药有限公司 | Pharmaceutical composition for treating bone diseases, injection thereof and preparation methods thereof |
| CN104127473B (en) * | 2014-07-31 | 2017-12-29 | 哈尔滨圣泰生物制药有限公司 | A kind of pharmaceutical composition for treating bone disease and its injection and preparation method |
| CN107988302A (en) * | 2018-01-23 | 2018-05-04 | 吉林省吉诺生物工程有限责任公司 | A kind of application of the preparation method and cervus and cucumis polypeptide of cervus and cucumis polypeptide in special medicine purposes food is prepared |
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Application publication date: 20090624 Assignee: Harbin Jier Biotechnology Co., Ltd. Assignor: Harbin Gloria Pharmaceuticals Co., Ltd. Contract record no.: 2014230000172 Denomination of invention: Cervus and cucumis polypeptide medicament composition oral preparation and preparation method thereof Granted publication date: 20120104 License type: Exclusive License Record date: 20140507 |
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Effective date of registration: 20170522 Address after: 150025, 29 Beijing Road, Limin economic and Technological Development Zone, Heilongjiang, Harbin Patentee after: Harbin Yu Heng Pharmaceutical Co., Ltd. Address before: 150090, 29 Beijing Road, Limin economic and Technological Development Zone, Heilongjiang, Harbin Patentee before: Harbin Gloria Pharmaceuticals Co., Ltd. |
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