CN1554667A

CN1554667A - Process for producing carboxymethyl pachyman

Info

Publication number: CN1554667A
Application number: CNA2003101116666A
Authority: CN
Inventors: 陈春霞; 林志彬
Original assignee: SANMING-CITY INST OF FUNGUSES
Current assignee: SANMING-CITY INST OF FUNGUSES
Priority date: 2003-12-26
Filing date: 2003-12-26
Publication date: 2004-12-15

Abstract

The industrial production process of synthesizing carboxymethyl pachyman with water as reaction medium includes the main steps of: extracting and alkalizing pachyman from wet tuckahoe powder with sodium hydroxide solution to obtain liquid A; neutralizing chloroactic acid solution with sodium hydroxide solution to obtain liquid B; and merging liquid A and liquid B and adding proper amount of sodium hydroxide solution to react under controlled reaction condition to obtain carboxymethyl pachyman. The said process needs no vibrating and stirring apparatus and thus has simplified production condition and low production cost. The produced carboxymethyl pachyman has high dissolubility, has quality reaching the requirement as food and medicine, and may be used in producing carboxymethyl pachyman oral liquid and injection.

Description

Production process of carboxymethyl pachyman

Technical Field

The invention belongs to the field of natural high molecular polysaccharides, and relates to a production process for synthesizing water-soluble carboxymethyl pachyman (CMP) by chemically modifying pachyman (Pachymran).

Background

Research reports [ journal of Chinese microbiology and immunology, 5 (5): 280(1985), journal of edible fungi, 3 (1): 27(1996), journal of edible fungi, 5 (2): 18(1998), Fujian TCM, 33 (3): 38(2002), carboxymethyl pachyman (CMP) has obvious inhibiting effect on mouse tumors U-14, S-180 sarcoma and liver cancer H22, can enhance the immune function of mice, and can induce human blood lymphocytes to produce natural cell activity factors such as interferon, interleukin, tumor necrosis factor and granulocyte-macrophage colony stimulating factor. Has application prospect as anti-tumor biological response regulator.

Hamuro et al (1971) prepared CMP bya liquid-solid phase oscillatory synthesis reaction using isopropanol water as a medium, which is a laboratory process only. Industrial production of CMP is technically difficult to realize because large-scale oscillation equipment is impossible. Post-treatment and purification of CMP products by Hamuro et al (1971) require large amounts of reagents such as ether, methanol, acetone, acetic acid and ethanol. If the industrial production is carried out, the discharge amount of waste water is large, and certain pollution is caused to the environment.

Shiqingdong et al (1996) adopt ethanol-water as a medium, and the liquid-solid phase stirring reaction is difficult to prepare CMP, and the large-scale industrial production is also difficult. The prepared CMP product has a carboxymethyl substitution degree (D, S) of 0.92, contains sodium chloride (NaCl) (%)<3.0 and heavy metal (calculated as Pb) (%)<0.002, and has low solubility (related to the carboxymethyl substitution degree) and high impurity content, so the product cannot be used as an injection medicament.

Disclosure of Invention

The invention aims to provide a production process of carboxymethyl pachyman. It uses water as reaction medium, and adopts a liquid-phase non-oscillation (or non-stirring) production method to adapt to the industrial production of CMP.

The chemical reaction formula for synthesizing the carboxymethyl pachyman is as follows:

in order to increase the degree of carboxymethyl substitution, the concentrations of chloroacetic acid and sodium hydroxide are correspondingly increased, so that sodium chloroacetate and sodium glycolate are also produced:

the concentration of chloroacetic acid and sodium hydroxide is increased, the effective collision frequency of the alkalized pachyman and sodium chloroacetate is increased, the carboxymethylation reaction rate can be accelerated, and the carboxymethyl substitution degree (D, S) can reach 1.0, so that the solubility of the carboxymethyl pachyman product is higher.

When the synthesis reaction is terminated, adjusting P with hydrochloric acid solution or sodium hydroxide solution^HThe value is 6.0-8.0, and the product contains not only CMP, but also low molecular weight substances and impurities such as chloride, sodium chloroacetate, sodium glycolate and the like. By usingThe ethanol precipitation method allows CMP to precipitate and be separated, but the precipitate still has a small amount of impurities attached.

Dissolving the dried CMP precipitate into 3.3-5.0% aqueous solution, and adjusting P with NaOH solution^HThe value is 9.0-12.0, and H is added₂O₂The amount of the solution is 0.5-1.0% of the solution, and the solution is decolorized at 10-60 ℃ for 2-48 hours to remove colored substances. Adjusting P with hydrochloric acid^HA value of 4.0 to 7.0, the molecular weight of 0.7X 10 is filtered off by an ultrafilter (molecular sieve)⁴Precipitating with ethanol, separating precipitate, washing with ethanol for 3 times, drying at 105 deg.C to constant weight to obtain high-purity active CMP product, which can be used as CMP oral liquid and CMP injection.

The liquid separated by the alcohol analysis CMP can be recycled by the recovered ethanol, the waste liquid after the ethanol recovery is combined with the waste liquid removed by ultrafiltration, and a proper amount of newly prepared lime water is added. At this time, the low molecular CMP, sodium chloroacetate and sodium glycolate in the waste liquid can react with the low molecular CMP, sodium chloroacetate and sodium glycolate to generate calcium salt precipitate to be removed, and the waste liquid only contains a small amount of NaCl to meet the requirement of environmental protection and discharge.

The carboxymethyl pachyman production process method provided by the invention does not need oscillation and stirring equipment, the carboxymethylation of pachyman is carried out by standing the liquid phase, the aims of simplifying the CMP production process and reducing the production cost are achieved, the CMP solubility (namely the carboxymethyl substitution degree (D, S)) is improved, the CMP quality meets the requirements of food and medicines, and the carboxymethyl pachyman can be used for producing CMP oral liquid and CMP injection.

Detailed Description

Pulverizing Poria 5.0kg, sieving with 80 mesh sieve, soaking in No. 1 glass-lined reaction tank (200L) for 14 hr, removing water, mixing wet Poria powder with 50L NaOH solution (1mol/L), standing for extraction and alkalizing for 30 min, centrifuging at 3000 rpm/min for 30 min, separating to obtain solution A, and removing residue. The solution A was transferred to a glass-lined reaction tank No. 2 (500L).

Cleaning No. 1 glass-lined reaction tank, adding 50L CLCH₂The COOH solution (2mol/L) was gradually neutralized with 25L of NaOH solution (4mol/L) to obtain solution B. And cooling the interlayer of the reaction tank with cold water in the reaction process.

Transferring the cooled solution B into a No. 2 glass lining reaction tank, mixing with the solution A, adding 16.9L of NaOH solution (4mol/L), and mixing uniformly. Heating the interlayer steam of the reaction tank to raise the temperatureof the synthetic reaction liquid to 70 ℃, and preserving the heat for 3 hours. After the reaction is finished, NaOH solution (4mol/L) or hydrochloric acid solution (4mol/L) is used for adjusting P^HAnd (3) adding ethanol with the volume being 2 times that of the reaction solution into the reaction solution with the value of 6.0-8.0, carrying out precipitation, separating the precipitate, drying the precipitate in a drying room at 80 ℃ for 2 hours, and drying the precipitate at 105 ℃ for 4 hours to obtain 2.5kg of the crude product of the carboxymethyl pachyman.

Dissolving 2.5kg of crude product of carboxymethyl pachyman in 60L of distilled water, and adjusting P with NaOH solution (4mol/L)^HThe value is 9.0 to 12.0. Then 30% of H was added₂O₂0.45L of solution, decoloring for 40 hours at room temperature, removing colored impurities, and regulating P with hydrochloric acid solution (4mol/L) after the decoloring reaction is finished^HThe value was 6.0, 3000 rpm/min for 30 minutes. Filtering the obtained filtrate with DH-UF hollow fiber ultrafilter (molecular sieve) to remove the molecular weight of 0.7 × 10⁴The following carboxymethyl pachyman and low molecular weight substance. Transferring the filtrate into a No. 2 glass-lined reaction tank, adding 3 times of ethanol, precipitating with ethanol, and separating precipitate. Washing precipitate with appropriate amount of ethanol for 3 times, draining, drying in drying room at 80 deg.C for 2 hr, drying at 105 deg.C for 4 hr, and pulverizing to obtain 2.0kg pure product of carboxymethyl pachyman. The carboxymethyl pachyman has a carboxymethyl substitution degree of 1.0. Collecting the filtrate throughEvaporating and recycling the recovered ethanol.

Carboxymethyl pachyman, white powder or floccule, and no odor.

IR[KBr](cm^-1)：3700～3000，2900，1600.7，1425.2，1324.9，1078.0，891.0。

UV(0.1mol/LHCl、H₂O, 0.1mol/LNaOH) has no absorption peak.

¹³C-NMR[H₂D](ppm) 180.078、104.870、87.697、86.667、84.935、83.145、77.851、

76.490、75.669、73.273、72.296、70.345、62.975。

[2]_D ²⁰：-1.70～1.90，(c＝5，H₂O) P^HA value of 4.0 to 7.0

Water content (%):<8.0 chloride (sodium chloride) (%):<0.01

Heavy metals (as Pb) (%):<0.001 arsenic (As) (%): is less than 0.0001.

Claims

1. A process for preparing carboxymethyl pachyman includes such steps as extracting wet tuckahoe powder with sodium hydroxide solution, alkalizing pachyman to obtain solution A, neutralizing chloroacetic acid solution with sodium hydroxide solution to obtain solution B, mixing A, B solutions, adding sodium hydroxide solution, controlling reaction condition, laying aside for reaction:

the weight ratio of the sodium hydroxide to the dry tuckahoe powder is 0.35-0.45: 1.0;

the weight ratio of the sodium hydroxide to the chloroacetic acid is 0.7-0.8: 1.0,

the weight ratio of the sum of the weight of the tuckahoe powder, the sodium hydroxide and the chloroacetic acid to the water is 1: 5-6.

2. The process for producing carboxymethylpachymaran according to claim 1, wherein the time for extracting and alkalizing pachymaran is 0.5-1.0 hour, and the carboxymethylation temperature is 61-74 ℃; the carboxymethylation time is 3-4 hours.

3. The process for producing carboxymethylpachymaran as claimed in claim 1, wherein after the completion of the synthesis reaction, the solution of hydrochloric acid or sodium oxide is used to adjust P^HThe value is 6.0-8.0, the generated carboxymethyl pachyman is precipitated by alcohol, and the volume ratio of the alcohol amount to the water amount is 2-3: 1.

4. The process for producing carboxymethyl pachyman according to claim 1, wherein the purification method of carboxymethyl pachyman is: dissolving the dried carboxymethyl pachyman polysaccharide alcohol precipitate and water according to the ratio of 1: 20-30, and adjusting the P of the solution by using sodium hydroxide solution^HThe value is 9.0-12.0, a hydrogen peroxide solution is used as a decoloring agent, the volume ratio of the hydrogen peroxide solution to the solution is 1: 100-200, the decoloring reaction temperature is 10-60 ℃, and the time is 2-48 hours; adjusting P with hydrochloric acid after reaction termination^HA value of 4.0 to 7.0, and a molecular weight of 0.7X 10 removed by an ultrafilter (molecular sieve)⁴The following carboxymethyl pachyman and other low molecular substances are re-precipitated by ethanol, and the volume ratio of the ethanol amount to the water amount is 2-3: 1.