CN113288917B - Preparation method of posterior pituitary extracting solution - Google Patents
Preparation method of posterior pituitary extracting solution Download PDFInfo
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- CN113288917B CN113288917B CN202110516266.1A CN202110516266A CN113288917B CN 113288917 B CN113288917 B CN 113288917B CN 202110516266 A CN202110516266 A CN 202110516266A CN 113288917 B CN113288917 B CN 113288917B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/04—Drugs for genital or sexual disorders; Contraceptives for inducing labour or abortion; Uterotonics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a posterior pituitary extracting solution, which comprises the following steps of taking a posterior pituitary stock solution, and carrying out rough filtration to obtain a filtrate end solution which is a solution 1; carrying out ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 10 KD-150 KD, controlling the flow rate of the solution 1 to be 20-60L/(square meter.h), taking a filtrate end solution as a solution 2, and taking a retentate end solution as a solution 3; continuously carrying out ultrafiltration on the solution 3, repeating the operation for many times, and taking a solution at the filtering end to obtain a solution 4; mixing the solution 2 and the solution 4 to obtain posterior pituitary extract; the method has the advantages of good impurity removal effect, high yield of active ingredients, high product safety and simple process.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a posterior pituitary extracting solution.
Background
The key raw material of posterior pituitary injection is posterior pituitary hormone, which is water-soluble component extracted from animal posterior pituitary and contains vasopressin (antidiuretic hormone) and oxytocin (oxytocin). The vasopressin can directly contract arterioles and capillaries (especially visceral blood vessels), can reduce portal vein pressure and pulmonary circulation pressure, and is favorable for thrombosis at vascular rupture to stop bleeding; but also increases the reabsorption of water by the renal tubules and collecting ducts. The oxytocin can enhance the rhythmic contraction of the uterus with a small dosage, and can cause the tonic contraction of the uterus with a large dosage, so that blood vessels in the myometrium are compressed to play a role in stopping bleeding.
The posterior pituitary extract is the raw material of the posterior pituitary injection, when the active ingredients in the posterior pituitary are extracted, some related substances with larger molecular weight can be extracted at the same time, and the high molecular weight impurities have no treatment effect in the medicine, can influence the stability and the curative effect of the medicine and even are harmful to the health of human bodies, so the removal of the high molecular weight impurities is particularly critical.
CN201510215900.2 discloses a purification method of posterior pituitary hormone. The method comprises the following steps:
(1) Mixing a posterior pituitary hormone stock solution with a buffer solution, wherein the pH value of the buffer solution is 3.0-5.0;
(2) Performing ultrafiltration by using an ultrafiltration membrane, and collecting trapped fluid;
(3) Diluting the trapped fluid with water, and adding acid to adjust the pH value of the solution to 1.0-2.0;
(4) Performing reverse ultrafiltration with ultrafiltration membrane, and collecting the filtrate.
The principle of impurity removal in the patent is that protein denaturation precipitation is carried out by adding acid, and then the protein denaturation precipitation is removed by filtration; the method can remove high molecular weight impurities in posterior pituitary extractive solution, and the obtained product has high purity, but needs two times of ultrafiltration, has high production cost and long production time, needs to add acid regulation solution, introduces new substances in the production process, and is not favorable for quality control of injection.
CN201510782736.3 discloses a production process of posterior pituitary injection, which relates to a process for removing impurities, and mainly comprises the steps of carrying out two-step ultrafiltration on an extracting solution obtained at the early stage by using a barrel type ultrafilter, filtering to obtain a posterior pituitary solution, and subpackaging and storing. Wherein the first step ultrafiltration membrane has a pore size of 0.4-0.5 μm; the second step of ultrafiltration with a filter membrane with the aperture of 0.2-0.3 μm; the preservation temperature of the treated filtrate is 0-10 ℃. The method removes impurities by ultrafiltration, but has large aperture and poor impurity removal effect.
In order to remove high molecular weight impurities, dialysis, gel chromatography or ultrafiltration technology is mainly adopted at present, wherein the concentration of a posterior pituitary extracting solution obtained by the dialysis technology is greatly reduced, the yield is lower, the production period is long, and the efficiency is low; the gel chromatography technology has poor separation effect on high molecular weight substances and active ingredients, small carrying capacity and high cost, and is not suitable for industrial production; the ultrafiltration technology can effectively separate the active ingredients from the high molecular weight impurities by utilizing the large difference of the molecular weight between the active ingredients and the impurities. CN201510215900.2 discloses a method for purifying posterior pituitary hormone, which uses ultrafiltration technology to solve the problem of high molecular weight substances, but the method needs two times of ultrafiltration, has high production cost and long production time, needs to add acid regulation solution, introduces new substances in the production process, and is not favorable for quality control of injection.
Disclosure of Invention
The invention aims to solve the technical problem of providing a preparation method of a posterior pituitary extracting solution, which has the advantages of good impurity removal effect, high yield of active ingredients, high product safety and simple process.
The invention relates to a method for preparing posterior pituitary extracting solution, which comprises the following steps,
taking a posterior pituitary raw liquid, and carrying out rough filtration to obtain a filtrate end solution which is a solution 1;
carrying out ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 10 KD-150 KD, controlling the flow rate of the solution 1 to be 20-60L/(square meter.h), taking a filtrate end solution as a solution 2, and taking a retentate end solution as a solution 3;
continuously carrying out ultrafiltration on the solution 3, repeating the operation for many times, and taking the solution at the filtering end to obtain a solution 4;
and mixing the solution 2 and the solution 4 to obtain a posterior pituitary extracting solution.
Preferably, the pore size of the coarse-filtered filter membrane is 0.2 to 1.0 micron.
Preferably, the solution 3 is continuously ultrafiltered, the molecular weight cut-off of a filter membrane for ultrafiltration is 10 KD-150 KD, and the flow rate is 20-60L/(m.h). Preferably, the step of subjecting solution 3 to ultrafiltration is the same as the step of subjecting solution 1 to ultrafiltration.
Preferably, the filter membrane for performing ultrafiltration on the solution 1 or the solution 3 is a filter membrane with the molecular weight cut-off of 30 KD-100 KD,
preferably, the flow rate for ultrafiltration of solution 1 or solution 3 is 30 to 50 liters/(m.h).
Preferably, the solution 1 or the solution 3 is ultrafiltered by a filter membrane with the molecular weight cut-off of 10 KD-20 KD, and the flow rate is 20-30L/(square meter hour).
Preferably, solution 3 is ultrafiltered at least 5 times, more preferably, solution 3 is ultrafiltered between 5 and 30 times, and more preferably, solution 3 is ultrafiltered between 10 and 20 times.
Preferably, when the solution 3 is continuously ultrafiltered, adding a buffer solution into the solution 3; preferably, the mass concentration of the acetic acid solution is 0.05-0.5%, preferably 0.1%.
The posterior pituitary dope can be various posterior pituitary dopes which are conventionally used in the field, and can be prepared by adopting the method disclosed in CN201510215900.2, namely, the following steps: the pituitary gland acetone soaking → the acetone of the stripped posterior lobe soaking → drying → crushing → acetone treatment → drying → crushing → acid extraction → activated carbon decoloration → filtration → obtaining the posterior lobe stock solution, and the posterior lobe stock solution is provided by the pharmaceutical company of Kangpu in Hunan province.
The ultrafiltration membrane is made of polyether sulfone or regenerated cellulose, preferably regenerated cellulose. The filter membranes made of different materials can adsorb active ingredients (vasopressin and oxytocin) in the posterior pituitary extracting solution, and the adsorbability of the regenerated cellulose is low.
The invention has the advantages that the ultrafiltration membrane is adopted to carry out ultrafiltration on the hypophysis posterior lobe stock solution, so that high molecular weight impurities are intercepted in the filtration membrane, micromolecular active ingredients can permeate the filtration membrane, the extract at the filtration end is collected, and the high molecular weight impurities can be basically removed. And finally, performing multiple dilution and reverse ultrafiltration on the extract which cannot permeate the filter membrane by adopting buffer solution with certain concentration, and collecting more than 90% of active ingredients at the filtering end.
The active ingredients and the high molecular weight impurities in the posterior pituitary extracting solution both have a plurality of hydrogen bonds in the structure, non-covalent bonds can be formed in water to cause agglomeration, and the agglomeration, especially the agglomeration between the high molecular weight impurities and the active ingredients, can obviously influence the ultrafiltration effect, so that the non-covalent bonds between the high molecular weight impurities and the active ingredients need to be broken by using some means to achieve the effects of separation and purification. To remove this agglomeration, the prior art generally employs the addition of acids, alkali or high temperature treatment to denature the agglomeration. The applicant discovers through preliminary research that the impact force of water flow in the ultrafiltration process has a certain effect on the damage of the noncovalent bonds, the method does not influence the stability and safety of the medicament, the cost is low, and the production feasibility is high, so that the flow rate of the extracting solution in the ultrafiltration process, the pressure born by the filter membrane, the material and the pore size of the filter membrane are all the key research contents of the project. The principle of the invention is that the impact force of water flow in the ultrafiltration process is utilized to separate high molecular weight impurities from active ingredients, thereby removing the impurities by ultrafiltration. The method adopts an ultrafiltration mode for 1 time to remove high molecular weight substances, does not add any other substances in the impurity removal process, and has safety, reliability and high production feasibility.
Researches show that the covalent bonds formed by the high molecular weight impurities and the active ingredients are broken, the covalent bonds are mainly related to the flow rate and the aperture size of ultrafiltration, the flow rate is too low, the impact force generated by the liquid medicine passing through the filter membrane is too small, the covalent bonds formed by the high molecular weight impurities and the active ingredients cannot be broken, and the active ingredients are intercepted by the ultrafiltration membrane along with the high molecular weight impurities when the high molecular weight impurities are removed, so that the yield is very low; if the flow rate is too high, the pressure difference between before and after filtration by the filter membrane increases, and there is a risk of rupture of the filter membrane. The larger the pore size of the filter membrane is, the larger the flow rate is required to meet the minimum requirement of separating active ingredients and impurities; the smaller the pore size, the relatively smaller the flow rate in order to meet the minimum requirements for separation of active ingredients and impurities.
The process has high feasibility, simple operation and low energy consumption; impurities are separated from active ingredients by adopting an impact force mode, and no acidic substance is added, so that the obtained preparation has higher safety; the impurity level is low, high molecular weight substances can be completely removed by the method, and more than 90% of active ingredients pass through the filter membrane by washing the solution at the interception end for many times, so that the yield is high.
Detailed Description
Example 1
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Taking posterior pituitary crude liquid, roughly filtering with a 1.0 micron filter membrane, and taking filtrate as solution 1;
(2) Performing ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 50 KD-100 KD, controlling the flow rate of the medicine liquid at the filtering end to be 30 liters/(square meter hour), taking the solution at the filtering end as a solution 2, and taking the solution at the intercepting end as a solution 3;
(3) Weighing the volume of the solution 3, adding an equal volume of buffer solution (acetic acid solution with the mass concentration of 0.1%) into the solution 3, continuing ultrafiltration (the same ultrafiltration step as the step (2)), repeating the operation for 10 times, and taking the filtrate end solution as a solution 4.
(4) And mixing the solution 2 and the solution 4 to obtain the posterior pituitary extracting solution.
Example 2
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Taking posterior pituitary raw liquid, carrying out rough filtration by adopting a 0.2 micron filter membrane, and taking a filtrate end solution as a solution 1;
(2) Carrying out ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 30KD, controlling the flow rate of the medicine liquid at the filtering end to be 20 liters/(square meter.h), taking the solution at the filtering end as a solution 2, and taking the solution at the intercepting end as a solution 3;
(3) Weighing solution 3, adding an equal volume of buffer (0.1% by mass acetic acid solution) into solution 3, continuing ultrafiltration (the same ultrafiltration step as step (2)), repeating the operation 20 times, and collecting filtrate as solution 4.
(4) And combining the solution 2 and the solution 4 to obtain the posterior pituitary extracting solution.
Example 3
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Taking posterior pituitary crude liquid, coarsely filtering with 0.8 micron filter membrane, and taking filtrate as solution 1;
(2) Carrying out ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 100KD, controlling the flow rate of the medicine liquid at the filtering end to be 50 liters/(square meter.h), taking the solution at the filtering end as a solution 2, and taking the solution at the intercepting end as a solution 3;
(3) Weighing the volume of the solution 3, adding an equal volume of buffer solution (0.1% by mass of acetic acid solution) into the solution 3, continuing ultrafiltration (the same ultrafiltration step as the step (2)), repeating the operation for 15 times, and taking the filtrate end solution as a solution 4.
(4) And combining the solution 2 and the solution 4 to obtain the posterior pituitary extracting solution.
Example 4
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Taking posterior pituitary raw liquid, carrying out rough filtration by adopting a 0.65 micron filter membrane, and taking a filtrate end solution as a solution 1;
(2) Carrying out ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 10KD, controlling the flow rate of the medicine liquid at the filtering end to be 25 liters/(square meter.h), taking the solution at the filtering end as a solution 2, and taking the solution at the intercepting end as a solution 3;
(3) Weighing the volume of the solution 3, adding an equal volume of buffer solution (acetic acid solution with the mass concentration of 0.1%) into the solution 3, continuing ultrafiltration (the same ultrafiltration step as the step (2)), repeating the operation for 30 times, and taking the filtrate end solution as a solution 4.
(4) And combining the solution 2 and the solution 4 to obtain the posterior pituitary extracting solution.
Example 5
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Taking posterior pituitary raw liquid, carrying out rough filtration by adopting a 0.45 micron filter membrane, and taking a filtrate end solution as a solution 1;
(2) Carrying out ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 50KD, controlling the flow rate of the medicine liquid at the filtering end to be 60 liters/(square meter.h), taking the solution at the filtering end as a solution 2, and taking the solution at the intercepting end as a solution 3;
(3) Weighing the volume of the solution 3, adding an equal volume of buffer solution (acetic acid solution with the mass concentration of 0.1%) into the solution 3, continuing ultrafiltration (the same ultrafiltration step as the step (2)), repeating the operation for 25 times, and taking the filtrate end solution as a solution 4.
(4) And mixing the solution 2 and the solution 4 to obtain the posterior pituitary extracting solution.
Comparative example 1
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Adding sodium acetate-acetic acid buffer solution (pH 3-5) into the extractive solution of posterior pituitary, and stirring.
(2) Ultrafiltering with ultrafiltration membrane with molecular weight cutoff of 2KDa, collecting the trapped fluid, and stopping ultrafiltration when the volume of the trapped fluid exceeds 90% of the initial volume of posterior pituitary ultrafiltration.
(3) Accurately measuring 200ml of the solution in the step (2), adding purified water according to 5 times of volume, and adjusting the pH value of the sample to 2.0 by adopting 2M HCl.
(4) And (3) performing ultrafiltration on the solution by adopting an ultrafiltration membrane with the molecular weight cutoff of 5KDa (the step of ultrafiltration is the same as the step (2)), collecting the ultrafiltration liquid, and stopping ultrafiltration when the volume of the ultrafiltration liquid reaches 90% of the ultrafiltration initial volume of posterior pituitary.
Comparative example 2
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Taking a posterior pituitary raw liquid, carrying out rough filtration by adopting a 2.0 micron filter membrane, and taking a filtrate end solution as a solution 1;
(2) Performing ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 5KD, controlling the flow rate of the medicine liquid at the filtering end to be 60 liters/(square meter hour), and taking the solution at the filtering end as a solution 2 and the solution at the intercepting end as a solution 3;
(3) Weighing the volume of the solution 3, adding an equal volume of buffer solution (0.1% by mass of acetic acid solution) into the solution 3, continuing ultrafiltration (the same ultrafiltration step as the step (2)), repeating the operation 30 times, and taking the filtrate end solution as a solution 4.
(4) And combining the solution 2 and the solution 4 to obtain the posterior pituitary extracting solution.
Comparative example 3
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Taking posterior pituitary crude liquid, roughly filtering with a 0.65 micron filter membrane, and taking filtrate as solution 1;
(2) Carrying out ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 200KD, controlling the flow rate of the medicine liquid at the filtering end to be 40 liters/(square meter.h), taking the solution at the filtering end as a solution 2, and taking the solution at the intercepting end as a solution 3;
(3) Weighing the volume of the solution 3, adding an equal volume of buffer solution (acetic acid solution with the mass concentration of 0.1%) into the solution 3, continuing ultrafiltration (the same ultrafiltration step as the step (2)), repeating the operation for 20 times, and taking the filtrate end solution as a solution 4.
(4) And mixing the solution 2 and the solution 4 to obtain the posterior pituitary extracting solution.
Comparative example 4
A method for preparing posterior pituitary extractive solution comprises the following steps,
(1) Taking posterior pituitary crude liquid, coarsely filtering with 0.45 micrometer filter membrane, and taking filtrate as solution 1;
(2) Performing ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 50KD, controlling the flow rate of the medicine liquid at the filtering end to be 10 liters/(square meter hour), and taking the solution at the filtering end as a solution 2 and the solution at the intercepting end as a solution 3;
(3) Weighing the volume of the solution 3, adding an equal volume of buffer solution (acetic acid solution with the mass concentration of 0.1%) into the solution 3, continuing ultrafiltration (the same ultrafiltration step as the step (2)), repeating the operation for 15 times, and taking the filtrate end solution as a solution 4.
(4) And combining the solution 2 and the solution 4 to obtain the posterior pituitary extracting solution.
The results of the high molecular weight impurity levels and the active ingredient yields for the above examples and comparative examples are shown in table 1 below:
TABLE 1 yield of impurities and effective ingredients of different groups
The high molecular weight substances are determined by molecular exclusion chromatography in Chinese pharmacopoeia 2020 edition.
Taking 1 count of ribonuclease A (molecular weight of 13700) control, human insulin (molecular weight of 5808) control, thymalfasin (molecular weight of 3108) control and somatostatin (molecular weight of 1638) control, dissolving with mobile phase, and diluting to obtain solutions each containing 1mg in 1ml, as molecular weight control solutions.
Hydrophilic modified silica gel is used as a filling agent (TSKgelG 2000SWXL column); trifluoroacetic acid-acetonitrile-water (0.5: 350: 650) as mobile phase; the detection wavelength is 214nm; the injection volume is 20 mu 1. Precisely measuring posterior pituitary extractive solution, injecting into liquid chromatograph, and calculating high molecular weight substance content of the sample by area normalization method.
As can be seen from table 1, the product yield of examples 4 and 5 is significantly higher than that of other examples, which indicates that the flow rate and the pore size of the ultrafiltration membrane need to satisfy a better matching relationship to achieve a better product yield.
As can be seen from the data of comparative example 1 and examples, the yield of the product was not ideal using the conventional ultrafiltration method, because although it effectively removed high molecular weight impurities, the retained material also contained a large amount of active ingredient, which was not effectively extracted.
From the analysis of example 4 and comparative example 2, it can be seen that even though the filter membrane is of good quality and can withstand the impact of a higher flow rate at a smaller pore size, the yield is not ideal, and the possible reason for this is that a portion of the active ingredient (molecular weight about 1 KD) can be separated from the high molecular weight impurities by the impact of the water flow, but the active ingredient itself will have some agglomeration, and if the pore size of the membrane is too small, the active ingredient will pass through with difficulty.
It can be seen from comparative example 3 that, although comparative example 4 and comparative example 3 have a high flow rate, comparative example 3 has a large pore size of the ultrafiltration membrane, the impact of water flow on the connecting bonds is small, and it is difficult to effectively separate high molecular weight impurities from active ingredients.
From the analysis of example 5 and comparative example 4 it can be seen that the flow rate is 60 litres/(m.h) at 50KD filter, significantly higher than at lower flow rates.
Those of ordinary skill in the art will understand that: the discussion of any embodiment above is meant to be exemplary only, and is not intended to intimate that the scope of the disclosure, including the claims, is limited to these examples; within the spirit of the present disclosure, features from the above embodiments or from different embodiments may also be combined, steps may be implemented in any order, and there are many other variations of different aspects of one or more embodiments in this application as described above, which are not provided in detail for the sake of brevity.
It is intended that the one or more embodiments of the present application embrace all such alternatives, modifications and variations as fall within the broad scope of the appended claims. Accordingly, any omissions, modifications, substitutions, improvements, and the like that may be made without departing from the spirit or scope of the disclosure are intended to be included within the scope of the disclosure.
Claims (10)
1. A preparation method of posterior pituitary extracting solution is characterized by comprising the following steps,
taking a posterior pituitary raw liquid, and carrying out rough filtration to obtain a filtrate end solution which is a solution 1;
carrying out ultrafiltration on the solution 1 by adopting a filter membrane with the molecular weight cutoff of 10 KD-150 KD, controlling the flow rate of the solution 1 to be 20-60L/(square meter.h), taking a filtrate end solution as a solution 2, and taking a retentate end solution as a solution 3;
continuously carrying out ultrafiltration on the solution 3, repeating the operation for many times, and taking the solution at the filtering end to obtain a solution 4;
mixing the solution 2 and the solution 4 to obtain posterior pituitary extract;
the ultrafiltration membrane is made of polyether sulfone or regenerated cellulose.
2. The method for preparing the liquid extract of posterior pituitary as claimed in claim 1, wherein the pore size of the coarse-filtered filter is 0.2 to 1.0 μm.
3. The method for preparing an extract of posterior pituitary as claimed in claim 1, wherein the solution 3 is further subjected to ultrafiltration with a membrane having a cut-off molecular weight of 10KD to 150KD and a flow rate of 20 to 60 liters per square meter hour.
4. The method for preparing the posterior pituitary extract according to claim 1, wherein the ultrafiltration membrane for the solution 1 or the solution 3 is a membrane having a molecular weight cut-off of 30-100 KD.
5. The method for producing the posterior pituitary extract according to claim 1, wherein the ultrafiltration is carried out at a flow rate of 30 to 50 liters/(m.h) per solution 1 or 3.
6. The method for preparing the posterior pituitary extract as claimed in claim 1, wherein the solution 1 or the solution 3 is ultrafiltered with a filter membrane having a molecular weight cut-off of 10 KD-20 KD at a flow rate of 20-30 l/(m.h).
7. The process for producing an extract liquid from the posterior pituitary according to any one of claims 1 to 5, wherein the ultrafiltration of the solution 3 is carried out at least 5 times.
8. The method for producing the posterior pituitary extract according to claim 6, wherein the ultrafiltration of the solution 3 is carried out 10 to 20 times.
9. The method for preparing the posterior pituitary extract according to claim 6, wherein the solution 3 is subjected to ultrafiltration, and a buffer is added to the solution 3.
10. The method according to claim 9, wherein the buffer solution is an acetic acid solution having a mass concentration of 0.05% to 0.5%.
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| CN113288917A (en) | 2021-08-24 |
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