CN106187746B - Method for preparing calcium citrate from fish scales and application of calcium citrate - Google Patents

Method for preparing calcium citrate from fish scales and application of calcium citrate Download PDF

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CN106187746B
CN106187746B CN201610596810.7A CN201610596810A CN106187746B CN 106187746 B CN106187746 B CN 106187746B CN 201610596810 A CN201610596810 A CN 201610596810A CN 106187746 B CN106187746 B CN 106187746B
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calcium citrate
calcium
fish scales
fish
scales
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CN106187746A (en
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陈勉
陈磊
于林艳
刘飞
张天娇
张秀华
张晓元
郝荣华
袁超
张金华
朱希强
凌沛学
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Shandong Academy of Pharmaceutical Sciences
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    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42Separation; Purification; Stabilisation; Use of additives

Abstract

The invention belongs to the technical field of aquatic product processing, and particularly relates to a method for preparing calcium citrate from fish scales and application of the calcium citrate. The invention provides a method for preparing calcium citrate from fish scale calcium, which comprises the following steps: (1) cleaning fish scales, fishing out the fish scales, weighing the fish scales, (2) adding a citric acid aqueous solution into the fish scales, stirring to obtain a calcium citrate suspension and decalcified fish scales, (3) sieving the obtained calcium citrate suspension and the decalcified fish scales through a sieve, filtering to obtain a calcium citrate suspension, and (4) carrying out solid-liquid separation on the obtained calcium citrate suspension, collecting precipitates, and drying to obtain the calcium citrate. The method can effectively dissolve the fish scale calcium and can separate out the free calcium ions to be converted into calcium citrate precipitates, and the calcium citrate can be obtained only by simple separation; the calcium citrate prepared by the invention is used for preparing the preparation for treating puerperal joint pain, and has remarkable clinical curative effect and high safety.

Description

Method for preparing calcium citrate from fish scales and application of calcium citrate
Technical Field
The invention belongs to the technical field of aquatic product processing, and particularly relates to a method for preparing calcium citrate from fish scales and application of the calcium citrate.
Background
Calcium citrate, C12H10Ca3O14·4H2O, molecular weight 570.49, its calcium content is 21.08%. It is an organic calcium, can be used as calcium supplement, and is easy to be absorbed and utilized by human body. The calcium citrate is produced through reaction between citric acid and calcium hydroxide and its calcium source is mainly calcium carbonate.
The fish scales are wastes generated in aquatic product processing, are rarely processed and utilized, and form putrescible solid garbage instead to breed flies and insects. The main calcium component of the fish scales is hydroxyapatite, and the calcium content is different according to different fish scale varieties. Research on chemical components of fish scales is advanced (the juanjuan and the like, Shanxi agricultural science, vol.39, No. 11, No. 1227 in 2011), calcium content of freshwater fish is 3.585% of carp scales, 5.953% of grass carp scales, 7.237% of crucian scales, and calcium content of marine fish such as large yellow croaker scales can reach up to 31.91%. When the fish scale calcium is completely converted into calcium citrate and completely collected, the corresponding recovery utilization rates of the calcium citrate are respectively 17.01 percent, 28.24 percent, 34.33 percent and 151.38 percent. It can be seen that the values are different depending on the specific fish scale sources and compositions, and comparing the values of the recycling rate of calcium citrate in isolation is not enough to judge the quality of the calcium extraction process.
Research on a process for removing calcium from fish scales by a citric acid method (Pengyuan and Huai, etc., agricultural machinery, 7/132 p. 2012), the calcium in the fish scales is removed by the citric acid, so that the total calcium content in the fish scales after the calcium removal treatment is reduced, the calcium removal rate of the fish scales is concerned, and the collection of calcium citrate is not needed. In this document, a decalcifying solution is obtained after treating fish scales with citric acid, and the calcium content in the decalcifying solution can be detected by EDTA (ethylene diamine tetraacetic acid) complexation titration, which indicates that the calcium citrate in the decalcifying solution is in a dissolved free ion state. The solubility of calcium citrate is very low (0.1 g/100mL water, 25 ℃), the solubility is increased when the pH value is reduced, if calcium citrate solid is extracted from a calcium citrate solution dissolved in a citric acid aqueous solution, the calcium citrate and the citric acid solution need to be separated, and the calcium citrate solution needs to be highly concentrated and solidified, so that the process is complex and the energy consumption is very high.
Chinese patent application No. 201210010943.3 discloses an antioxidant calcium-supplementing fish scale peptide calcium compound chewable tablet and a preparation method thereof, wherein citric acid is adopted to convert calcium in fish scales into calcium citrate. The method comprises the steps of drying, crushing and enzymolysis filtering of fish scales, finally adding citric acid into filter residue for conversion, and collecting precipitate to obtain calcium citrate. The process is complicated and high in cost, and the obtained precipitate is complex in composition, and not only can contain fish scale residues which are not completely enzymolyzed, but also can contain hydroxyapatite which does not react with citric acid, so that the content of calcium citrate in the precipitate is not high. For calcium citrate products alone, the process steps of drying and crushing the fish scales are also added.
The retrieval finds that the existing methods for removing calcium from fish scales mainly comprise an acid method and an EDTA method, and the principle is that hydroxyapatite Ca is extracted by using an extracting solution10(OH)2(PO4)6The calcium in the calcium carbonate is dissolved or complexed, the replaced calcium ions are dissociated in the solution, the recovery and the utilization are very troublesome, the acid amount commonly used by the processes is large, the resources are wasted, the production cost is increased, and the economic utilization of the resources is not facilitated.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides the method for preparing the calcium citrate from the fish scales, the method is simple to operate, and the obtained calcium citrate has high purity and is easy for industrial production.
In addition, the invention also provides an application of the calcium citrate in preparing a preparation for treating puerperal joint pain,
in order to achieve the purpose, the invention adopts the following technical scheme:
a method for preparing calcium citrate from fish scale calcium comprises the following steps:
(1) cleaning fish scales, fishing out the fish scales and weighing the fish scales;
(2) adding a citric acid aqueous solution into the fish scales in the step (1), and stirring to obtain a calcium citrate suspension and decalcified fish scales;
(3) sieving the calcium citrate suspension obtained in the step (2) and the decalcified fish scales through a screen and filtering to obtain a calcium citrate suspension;
(4) and (4) carrying out solid-liquid separation on the calcium citrate suspension obtained in the step (3), collecting the precipitate, and drying to obtain the calcium citrate.
A method for preparing calcium citrate from fish scales preferably comprises the following operation methods:
(1) cleaning fish scales, fishing out wet fish scales, and weighing, wherein the water content of the wet fish scales is 50-75 wt%;
(2) adding a citric acid aqueous solution into the wet fish scales obtained in the step (1), adjusting the temperature of the solution to be 15-35 ℃, stirring, and obtaining a suspension containing calcium citrate and decalcified fish scales when the pH of the solution reaches 3.5-6.5; wherein the concentration of the citric acid aqueous solution is 1.2-3.9 wt%; wherein the stirring speed is 100-300 rpm; preferably, the temperature of the adjusting solution is 20-30 ℃, the pH is 4-6, and the concentration of the citric acid aqueous solution is 2.0-3.8 wt%;
(3) filtering the calcium citrate suspension and the decalcified fish scales in the step (2) through a screen with the aperture of 50-100 meshes to obtain a calcium citrate suspension;
(4) carrying out solid-liquid separation on the calcium citrate suspension obtained in the step (3), collecting calcium citrate precipitate, drying and crushing to obtain calcium citrate; the solid-liquid separation method is centrifugation or plate-frame filtration.
A calcium citrate prepared by the preparation method.
Application of the calcium citrate in preparing a preparation for treating puerperal joint pain is provided.
The preparation for treating puerperal postpartum arthralgia is in a capsule form.
The preparation method of the invention does not need links such as drying and crushing the fish scales, but makes full use of the large sheet shape of the fish scales to form shape contrast with the uniformly dispersed decalcified white pulp, and is easy to realize the separation of the fish scale residues and the calcium citrate white pulp through a common screen. On the other hand, the hydroxyapatite is a component of the fish scales, only the part dissolved in the citric acid can be dissociated from the whole fish scales, the undissolved hydroxyapatite is continuously remained in the fish scale tissues, and the undissolved hydroxyapatite is blocked while the fish scales are intercepted by the screen. Therefore, the method is simple and convenient, and the obtained calcium citrate has less impurities.
Advantageous effects
(1) According to the invention, by controlling the concentration of the citric acid aqueous solution added into wet fish scales and the pH of the reacted solution, the fish scale calcium can be effectively dissolved, and the free calcium ions can be separated and converted into precipitates, and the calcium citrate can be obtained only by simple separation.
(2) The calcium citrate prepared by the invention is applied to the preparation of the preparation for treating puerperal joint pain, the citric acid aqueous solution can effectively dissolve calcium ions, and simultaneously can properly dissolve elements such as zinc, magnesium, phosphorus and the like in fish scales which are beneficial to human bodies, and the proper amount of magnesium and phosphorus can enhance the absorption of calcium by puerperal women; the zinc is one of trace elements necessary for human bodies and plays an important role in physical recovery processes of immunity, internal secretion and the like of lying-in women, so that the compound nutrient component mixture ratio mainly containing the calcium citrate element prepared by the invention is suitable for the requirements of the body absorption function of the lying-in women, has obvious clinical curative effect and high safety, and is particularly suitable for being applied to a preparation for treating the postpartum arthralgia of the lying-in women.
Detailed Description
The present invention will be further described with reference to examples and comparative examples, but it should be noted that the following description is only for the purpose of explaining the present invention and does not limit the contents thereof.
(1) Rinsing fish scales with water to remove blood stains, floating fish membranes and other foreign matters, fishing out wet fish scales and weighing 1kg of the wet fish scales, wherein the water content of the wet fish scales is 50-75 wt%;
(2) adding a citric acid aqueous solution into the wet fish scales obtained in the step (1), adjusting the temperature of the solution to be 15-35 ℃, stirring, and obtaining a suspension containing calcium citrate and decalcified fish scales when the pH of the solution reaches 3.5-6.5; wherein the concentration of the citric acid aqueous solution is 1.2-3.9 wt%;
(3) filtering the calcium citrate suspension and the decalcified fish scales in the step (2) through a screen with the aperture of 50-100 meshes to obtain a calcium citrate suspension;
(4) and (4) carrying out solid-liquid separation on the calcium citrate suspension obtained in the step (3), collecting calcium citrate precipitate, drying and crushing to obtain the calcium citrate.
The process parameters for each example and comparative example are shown in table 1:
Figure DEST_PATH_IMAGE001
the calcium citrate and the decalcified fish scales prepared by the above examples and comparative examples are used for detecting each index, wherein the detection method of each index is as follows:
the content of calcium citrate is detected according to the GB 17203-1998 calcium citrate (currently available) method as a food additive;
calcium extraction rate% = (calcium citrate product content of fish scale: 21%/total calcium content of raw material fish scale) = 100%; the method for measuring total calcium in fish scales comprises the following steps: cutting dried fish scales into small pieces with the length and the width of 3 millimeters, accurately weighing a certain amount of the crushed fish scales in 1mol/L hydrochloric acid solution with the material-liquid ratio of 1:20, reacting at room temperature for 24 hours, transferring the decalcified liquid into a volumetric flask, washing the fish scales with distilled water, transferring the washing liquid into the volumetric flask together, and titrating the total calcium content in the fish scales with EDTA standard solution;
detecting the content of Mg and Zn elements by an atomic absorption spectrophotometer;
detecting the content of the P element by a plasma emission spectrometer;
the results of the measurements for each index are shown in table 2:
Figure DEST_PATH_IMAGE002
as can be seen from table 2: compared with the prior art, the scale decalcification degree of the scales of the comparative examples 1 and 2 is low, a small amount of calcium citrate is formed in the fluid to obtain white turbid liquid, and the collection of the calcium citrate is not facilitated; the low pH of comparative example 3 indicates a large amount of citric acid residue, which not only wastes the raw material citric acid, but also increases the solubility of calcium citrate to cause filtration loss; the comparative example 4 has larger residual quantity of citric acid and obvious solubilization effect on calcium citrate, so that the calcium citrate cannot be effectively separated out to form precipitate and cannot be collected in one step; comparative example 5 calcium dissolved in hydroxyapatite, a large amount of calcium citrate formed compact precipitated crystals inside and outside the fish scales, and could not be separated from the fish scales and collected. While the calcium citrate content in the calcium citrate prepared in the embodiments 1-5 is 90-99%, the extraction rate of calcium in fish scales is 90-98%, the magnesium content is 250-950 mg/kg, the zinc content is 8-180 mg/kg, the phosphorus content is 0.2-1.5%, the liquid fluid is white and thick in appearance, and the fish scales are transparent, which shows that the operation method in the embodiments of the invention can effectively decalcify, can further precipitate to collect high-purity calcium citrate, and the rest of the citric acid is small, and the utilization rate is high.
The calcium citrate extracted in the embodiment 1-5 is a compound multi-nutrient component taking calcium citrate as a main component, and the element proportion is suitable for the absorption function requirement of the body of the lying-in woman; proper amount of magnesium and phosphorus can enhance the absorption of calcium by puerpera; zinc is one of essential trace elements, and has important effect on physical recovery process of lying-in women including immunity, endocrine and the like.
Example 6 preparation of Fish Scale calcium citrate capsules
Powder mixing:
10g of vitamin D3 and 90g of calcium citrate (prepared in example 2) were weighed and mixed in a powder mixer having a volume of 0.1L to obtain mixed powder 1 (vitamin D3 in a weight ratio of 10.00%). 100g of the mixed powder 1 and 900g of the fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 1L to obtain mixed powder 2 (the weight of the vitamin D3 is 1.00 percent). 1kg of mixed powder 2 and 9kg of fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 10L to obtain mixed powder 3 (the weight ratio of vitamin D3 is 0.10%). 10kg of mixed powder 3 and 90kg of fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 100L to obtain mixed powder 4 (the weight of vitamin D3 is 0.01%). 100kg of mixed powder 4 was mixed with 900kg of fish scale calcium citrate in a 1000L powder mixer to obtain mixed powder 5 (vitamin D3 in an amount of 0.001 wt%). 100kg of mixed powder 5 is taken and mixed with 400kg of fish scale calcium citrate uniformly in a powder mixer with the volume of 600L to obtain mixed powder 6 (the weight ratio of vitamin D3 is 2.0 ppm).
Filling fish scale calcium citrate capsules:
selecting a No. 0 capsule shell, and preparing the mixed powder 6 powder into the fish scale calcium citrate capsule by a full-automatic capsule filling machine according to the loading capacity of 800 +/-40 mg/granule.
Example 7 preparation of Fish Scale calcium citrate capsules
Powder mixing:
10g of vitamin D3 and 90g of calcium citrate (prepared in example 1) were weighed and mixed in a powder mixer having a volume of 0.1L to obtain mixed powder 1 (vitamin D3 weight ratio: 10.00%). 100g of the mixed powder 1 and 900g of the fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 1L to obtain mixed powder 2 (the weight of the vitamin D3 is 1.00 percent). 1kg of mixed powder 2 and 9kg of fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 10L to obtain mixed powder 3 (the weight ratio of vitamin D3 is 0.10%). 10kg of mixed powder 3 and 90kg of fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 100L to obtain mixed powder 4 (the weight of vitamin D3 is 0.01%). 100kg of mixed powder 4 was mixed with 900kg of fish scale calcium citrate in a 1000L powder mixer to obtain mixed powder 5 (vitamin D3 in an amount of 0.001 wt%). 100kg of mixed powder 5 is taken and mixed with 300kg of fish scale calcium citrate uniformly in a powder mixer with the volume of 500L to obtain mixed powder 6 (the weight of the vitamin D3 is 2.5 ppm).
Filling fish scale calcium citrate capsules:
selecting a No. 0 capsule shell, and preparing the mixed powder 6 powder into the fish scale calcium citrate capsule by a full-automatic capsule filling machine according to the loading capacity of 800 +/-40 mg/granule.
Example 8 preparation of Fish Scale calcium citrate capsules
Powder mixing:
10g of vitamin D3 and 90g of calcium citrate (prepared in example 3) were weighed and mixed in a powder mixer having a volume of 0.1L to obtain mixed powder 1 (vitamin D3 weight ratio: 10.00%). 100g of the mixed powder 1 and 900g of the fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 1L to obtain mixed powder 2 (the weight of the vitamin D3 is 1.00 percent). 1kg of mixed powder 2 and 9kg of fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 10L to obtain mixed powder 3 (the weight ratio of vitamin D3 is 0.10%). 10kg of mixed powder 3 and 90kg of fish scale calcium citrate are uniformly mixed in a powder mixer with the volume of 100L to obtain mixed powder 4 (the weight of vitamin D3 is 0.01%). 100kg of mixed powder 4 was mixed with 900kg of fish scale calcium citrate in a 1000L powder mixer to obtain mixed powder 5 (vitamin D3 in an amount of 0.001 wt%). 100kg of mixed powder 5 is taken and mixed with 230kg of fish scale calcium citrate uniformly in a powder mixer with the volume of 400L to obtain mixed powder 6 (the weight ratio of vitamin D3 is 3.0 ppm).
Filling fish scale calcium citrate capsules:
selecting a No. 0 capsule shell, and preparing the mixed powder 6 powder into the fish scale calcium citrate capsule by a full-automatic capsule filling machine according to the loading capacity of 800 +/-40 mg/granule.
Comparative example 6 preparation of food grade calcium citrate capsules
Powder mixing:
weighing 10g of vitamin D3 and 90g of food-grade calcium citrate (the content of calcium citrate is more than 99.9 percent of the commercially available food-grade calcium citrate), and uniformly mixing in a powder mixer with the volume of 0.1L to obtain mixed powder 1 (the weight of the vitamin D3 accounts for 10.00 percent). 100g of the mixed powder 1 is mixed with 900g of food-grade calcium citrate uniformly in a powder mixer with the volume of 1L to obtain mixed powder 2 (the weight of the vitamin D3 is 1.00 percent). 1kg of mixed powder 2 is mixed with 9kg of food-grade calcium citrate uniformly in a powder mixer with the volume of 10L to obtain mixed powder 3 (the weight ratio of vitamin D3 is 0.10%). And (3) mixing 10kg of mixed powder 3 with 90kg of food-grade calcium citrate uniformly in a powder mixer with the volume of 100L to obtain mixed powder 4 (the weight of the vitamin D3 is 0.01%). 100kg of mixed powder 4 is mixed with 900kg of food-grade calcium citrate uniformly in a powder mixer with the volume of 1000L to obtain mixed powder 5 (the weight ratio of vitamin D3 is 0.001%). 100kg of mixed powder 5 is taken and mixed with 300kg of food-grade calcium citrate uniformly in a powder mixer with the volume of 500L to obtain mixed powder 6 (the weight ratio of vitamin D3 is 2.5 ppm).
Filling fish scale calcium citrate capsules:
selecting a No. 0 capsule shell, and preparing the mixed powder 6 into food-grade calcium citrate capsules by using a full-automatic capsule filling machine according to the loading of 800 +/-40 mg/capsule.
Efficacy testing
Postpartum arthralgia is a common disorder after childbirth for women. Common traditional Chinese medicine massage, fumigation and other methods can effectively relieve postpartum arthralgia, but the method needs a professional to try out on each case and is difficult to popularize and apply in a large area. Parturient suffers from the influence of hormone change in vivo, particularly has the history of excessive blood loss during delivery and postpartum, has more bone loss, and is easy to have symptoms of bone joint ache, pain and unfavorable flexion and extension after suffering from wind cold, dampness and cold. The calcium supplement can supplement calcium nutrition, strengthen bone of parturient, and improve puerperal arthralgia.
1. Test object
160 parturients with normal childbirth and postpartum arthralgia, which had the shortest disease course of 1 week and the longest disease course of 6 months after the age of 22-38 years, were selected and randomly divided into 4 groups, wherein 3 groups used the fish scale calcium citrate capsules prepared in example 6, example 7 and example 8, respectively, 1 group was a control group, and calcium citrate capsules prepared in the comparative example were used, and there was no significant difference in age and symptoms among the groups.
2. Application method
Example set: 1 granule/time, 2 granules/time in lactation period, 2 times/day, and continuous administration for 8 weeks.
The control group was administered in the same manner as the test group.
3. Standard of therapeutic effect
(1) The method has the following advantages: the pain joint number is reduced, the pain degree is reduced, and the morning stiffness time is shortened
(2) And (4) invalidation: the pain joint number is unchanged or increased, the pain degree is increased, and the morning stiffness time is unchanged or prolonged
4. And (3) test results:
(1) adverse reaction
Neither the test group nor the control group has adverse reactions such as allergy, abdominal distension and the like.
(2) Improvement effect on postpartum arthralgia
The results are shown in Table 3
Comparison of usage effects of fish scale calcium citrate
Figure 867275DEST_PATH_IMAGE003
As can be seen from Table 3, the fish scale calcium citrate capsule prepared by the invention has good effect of improving postpartum arthralgia, can effectively relieve symptoms related to postpartum pain, and has no adverse reaction. In addition, experiments prove that the fish scale calcium citrate can effectively improve joint pain after being used for 3-4 weeks, and can realize the function of quickly maintaining postpartum joints.

Claims (4)

1. A method for preparing calcium citrate from fish scale calcium is characterized by comprising the following steps:
(1) cleaning fish scales, fishing out wet fish scales, and weighing, wherein the water content of the wet fish scales is 50-75 wt%;
(2) adding a citric acid aqueous solution into the wet fish scales obtained in the step (1), adjusting the temperature of the solution to be 15-35 ℃, stirring, and preparing for filtering when the pH of the solution reaches 3.5-6.5 to obtain a white thick suspension containing calcium citrate and transparent decalcified fish scales; wherein the concentration of the citric acid aqueous solution is 1.2-3.9 wt%;
(3) filtering the white thick calcium citrate suspension and the transparent decalcified fish scales in the step (2) through a screen with the aperture of 50-100 meshes to obtain a calcium citrate suspension;
(4) and (4) carrying out solid-liquid separation on the calcium citrate suspension obtained in the step (3), collecting calcium citrate precipitate, drying and crushing to obtain the calcium citrate.
2. The method for preparing calcium citrate from fish scale calcium as claimed in claim 1, wherein the stirring speed in step (2) is 100-300 rpm.
3. The method for preparing calcium citrate from fish scale calcium as claimed in claim 1, wherein the temperature of the adjusting solution in step (2) is 20-30 ℃, the pH is 4-6, and the concentration of the citric acid aqueous solution is 2.0-3.8 wt%.
4. The method for preparing calcium citrate from fish scale calcium according to claim 1, wherein the solid-liquid separation method in step (4) is centrifugation or plate and frame filtration.
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US20050112211A1 (en) * 2003-08-21 2005-05-26 Eric Gervais Micronutrient supplement
CN101307348A (en) * 2008-06-13 2008-11-19 华中农业大学 Method for preparing undenatured collagen from fish scale of fresh water fish
CN103202419A (en) * 2012-01-15 2013-07-17 华中农业大学 A compound fish scale peptide and calcium compound chewable tablet for antioxidation and calcium supplementing and a preparation method thereof

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Publication number Priority date Publication date Assignee Title
US20050112211A1 (en) * 2003-08-21 2005-05-26 Eric Gervais Micronutrient supplement
CN101307348A (en) * 2008-06-13 2008-11-19 华中农业大学 Method for preparing undenatured collagen from fish scale of fresh water fish
CN103202419A (en) * 2012-01-15 2013-07-17 华中农业大学 A compound fish scale peptide and calcium compound chewable tablet for antioxidation and calcium supplementing and a preparation method thereof

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Title
鱼鳞胶原蛋白的提取及凝胶性质的研究;邵昆;《中国优秀硕士论文全文数据库工程科技I辑》;20130715;第B024-167页 *

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