CN114748445B - High-vitamin A acetate particle and preparation method thereof - Google Patents
High-vitamin A acetate particle and preparation method thereof Download PDFInfo
- Publication number
- CN114748445B CN114748445B CN202210519778.8A CN202210519778A CN114748445B CN 114748445 B CN114748445 B CN 114748445B CN 202210519778 A CN202210519778 A CN 202210519778A CN 114748445 B CN114748445 B CN 114748445B
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- vitamin
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- acetate
- oil
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Classifications
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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Abstract
The application relates to a high-content vitamin A acetate particle and a preparation method thereof. Compared with the spray granulation method, the direct physical mixing granulation method improves the bioavailability and the stability of the preparation, increases the retention rate of vitamin A acetate in the preparation, reduces related substances, and has obvious superiority compared with other vitamin A acetate particles.
Description
Technical Field
The application relates to the field of biological medicines and food and feed, in particular to a high-content vitamin A acetate particle and a preparation method thereof.
Background
Vitamin a (vitamine a), also known as retinol (its aldehyde derivative, retinaldehyde), is a fat-soluble alcohol, in a variety of molecular forms. Wherein VA1 is mainly present in the retina of the animal liver, blood and eyeball.
Vitamin a is a nutrient necessary for complex organisms and affects almost all tissue cells of the organism in different ways. Although it is the earliest vitamin discovered, its physiological function has not been completely uncovered until now. To the current knowledge, vitamin a (including carotenes) is the most important physiological function including: 1. vision is maintained: vitamin a can promote the formation of photopigments in visual cells. All-trans retinal can be catalyzed by retinal isomerase to 4-cis-retinal, and 4-cis-retinal can be combined with opsin to rhodopsin (rhodopsin). The 4-cis-retinal in rhodopsin turns into full-trans-retinal after encountering light, and the visual stimulus is caused by the change of conformation, so that vision is caused. And the rhodopsin after exposure to light is unstable and is rapidly decomposed into opsin and total reverse retinoid, and the whole circulation process is restarted. The vitamin A can regulate the capability of the eyes to adapt to the intensity of external light so as to reduce the occurrence of night blindness and vision deterioration, maintain normal visual response and be beneficial to the treatment of various eye diseases (such as xerophthalmia, conjunctivitis and the like). Vitamin a is the earliest discovered and most known function of vision. 2. Promoting growth and development: retinol also has an action equivalent to steroid hormone, which promotes glycoprotein synthesis. Promoting growth and development, strengthening bone, and maintaining hair, teeth and gum health. 3. Maintaining the integrity of the epithelial structure: retinol and retinoic acid regulate gene expression, attenuate epithelial cell differentiation into scaly forms, and increase the number of epithelial growth factor receptors. Thus, vitamin A can regulate the growth of epithelial tissue cells and maintain the normal morphology and function of epithelial tissue. The skin is kept moist, the skin mucous membrane is prevented from being dried and keratinized, and the skin mucous membrane is not easy to be damaged by bacteria, thereby being beneficial to the treatment of acne, pustule, furuncle, skin surface ulcer and other diseases; is helpful for removing senile plaques; can maintain the health of tissue or organ surface. The deficiency of vitamin a can reduce the function of epithelial cells, leading to reduced skin elasticity, dry roughness, and loss of gloss. 4. Enhancing immunity: vitamin A helps to maintain immune system normal, and can strengthen body resistance to infectious diseases, especially respiratory tract infection and parasitic infection; is useful for treating emphysema and hyperthyroidism. 5. Scavenging free radicals: vitamin A also has certain antioxidation effect, and can neutralize harmful free radicals. In addition, many studies have shown that skin, lung, throat, bladder and esophagus cancers are all related to vitamin a intake; however, these studies remain to be clinically proven even further.
The vitamin A commonly used in the prior art is vitamin A acetate, is yellow prismatic crystal, is insoluble in water, and is easily dissolved in ethanol, oil, chloroform and diethyl ether. The vitamin A is more stable than vitamin A and is often prepared into a preparation form of microparticle powder, and the preparation process is to add an antioxidant and gelatin to prepare microparticles through spraying, but the microparticles are easy to absorb moisture, heat and acid gas or decompose after being subjected to visible light or moisture absorption, so that the content is reduced.
The prior art vitamin A acetate microparticles are prepared by spray granulation. Such as: in CN104186976a vitamin a acetate was added to an emulsifying pot and sprayed to a fluidized bed to prepare microparticles. In CN114315675A, vitamin A acetate crystals are added into carrier emulsion, and then spray granulation is carried out to prepare the vitamin A acetate particles.
Because the vitamin A acetate has extremely poor water solubility, can not be fully absorbed and utilized by animals, and has the problems of poor stability and easy oxidation. In the prior art CN105104759A and CN106667920A, the performance of the vitamin A acetate particles is improved by adding an emulsifier Tween, maltodextrin, polyethylene glycol and the like.
Therefore, there is a need in the art for a preparation method or process that can improve the stability, bioavailability, etc. of vitamin a acetate particles without adding other ingredients.
Disclosure of Invention
The present application has found during experiments that high levels of vitamin a acetate particles, especially vitamin a acetate particles in excess of 20%, have a dramatic decrease in stability. The vitamin A acetate particles with improved stability are obtained through screening of auxiliary materials and the dosage of the auxiliary materials, and compared with the vitamin A acetate particles with low content, the vitamin A acetate particles have higher bioavailability.
Furthermore, the preparation process is physical mixing, avoids a spray granulation method generally adopted in the prior art, avoids the addition of water and organic solvents, and reduces the process steps. Compared with the spray granulation method, the direct physical mixing granulation method improves the bioavailability and the stability of the preparation, increases the retention rate of vitamin A acetate in the preparation, reduces related substances, and has obvious superiority compared with other vitamin A acetate particles.
The application provides a preparation method of high-content vitamin A acetate particles, which is characterized by comprising the following steps of: adding 300-500 parts by mass of vitamin A acetate and 15-40 parts by mass of antioxidant into a container, heating under the protection of non-oxygen gas, stirring and dissolving to obtain vitamin A oil; and 50-200 parts by mass of gelatin: kappa-type (kappa) carrageenan = 2:1 mixture, 200-800 parts by mass lactose: mixing mannitol=3:1 mixture, 120-600 parts by mass of corn starch and 5-20 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and sieving to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis sieve with a pore diameter of 0.84mm, the moisture is less than or equal to 5%, the weight metal content of Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
The preparation method is characterized in that the non-oxygen gas is one or more of nitrogen, inert gas and carbon dioxide.
The preparation method is characterized in that the antioxidant is one or more of 2, 6-di-tert-butyl-4-methylphenol (BHT), ethoxyquinoline, vitamin C and citric acid.
The preparation method is characterized by further comprising the steps of detecting and packaging, sampling the vitamin A acetate particles, mixing the particles after the particles are detected to be qualified, and detecting, packaging and warehousing the particles after the particles are detected to be qualified.
The preparation method is characterized in that 400 parts by mass of vitamin A acetate and 20 parts by mass of antioxidant are added into a container, and the mixture is heated and stirred for dissolution under the protection of non-oxygen gas to obtain vitamin A oil; 94 parts by mass of gelatin: kappa-type (kappa) carrageenan = 2:1 mixture, 300 parts by mass lactose: uniformly mixing a mannitol=3:1 mixture, 176 parts by mass of corn starch and 10 parts by mass of silicon dioxide in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to perform grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and screening to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles can pass through an analysis screen with a pore diameter of 0.84mm, the moisture is less than or equal to 5%, the weight metal content calculated by Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
The preparation method is characterized in that the container is an oil dissolving kettle.
The preparation method as described above, characterized in that more than 99.5% of the vitamin a acetate particles pass through an analytical sieve with a pore size of 0.84 mm.
The preparation method is characterized in that 100% of vitamin A acetate particles pass through an analysis sieve with a pore diameter of 0.84 mm.
In addition, the application also provides a preparation method of the vitamin A acetate particles, which is characterized in that: adding 100-400 parts by mass of vitamin A acetate and 1-15 parts by mass of antioxidant into a container, heating under the protection of non-oxygen gas, stirring and dissolving to obtain vitamin A oil; and mixing 50-200 parts by mass of gelatin, 200-800 parts by mass of sugar filler, 120-600 parts by mass of corn starch and 5-20 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating so as to effectively coat the vitamin A oil and powder wall materials, and screening to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis screen with the aperture of 0.84mm, the moisture is less than or equal to 5%, the Pb weight metal content is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
The preparation method is characterized in that the non-oxygen gas is as follows: nitrogen, inert gas, carbon dioxide.
The preparation method is characterized in that the sugar filling agent is one or more of sucrose, white granulated sugar, glucose, lactose, galactose and fructose.
The preparation method is characterized in that the antioxidant is one or more of 2, 6-di-tert-butyl-4-methylphenol (BHT), ethoxyquinoline, vitamin C and citric acid.
The preparation method is characterized by further comprising the steps of detecting and packaging, sampling the vitamin A acetate particles, mixing the particles after the particles are detected to be qualified, and detecting, packaging and warehousing the particles after the particles are detected to be qualified.
The preparation method is characterized in that 200 parts by mass of vitamin A acetate and 6 parts by mass of antioxidant are added into a container, and the mixture is heated and stirred for dissolution under the protection of non-oxygen gas to obtain vitamin A oil; and mixing 100 parts by mass of gelatin, 400 parts by mass of sugar filler, 284 parts by mass of corn starch and 10 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and sieving to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the weight metal content of Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
The preparation method is characterized in that 400 parts by mass of vitamin A acetate and 12 parts by mass of antioxidant are added into a container, and the mixture is heated and stirred for dissolution under the protection of non-oxygen gas to obtain vitamin A oil; and mixing 94 parts by mass of gelatin, 300 parts by mass of sugar filler, 184 parts by mass of corn starch and 10 parts by mass of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to carry out grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and sieving to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the weight metal content of Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
The preparation method is characterized in that the container is an oil dissolving kettle.
The application also provides vitamin A acetate particles, which are characterized by being prepared by the preparation process.
The preparation process is physical mixing, avoids a spray granulation method generally adopted in the prior art, avoids the addition of water and organic solvents, and reduces the process steps. Compared with the spray granulation method, the direct physical mixing granulation method improves the bioavailability and the stability of the preparation, increases the retention rate of vitamin A acetate in the preparation, reduces related substances, and has obvious superiority compared with other vitamin A acetate particles.
Drawings
Fig. 1: process flow diagram
Detailed Description
Example 1: preparation of 20% vitamin a acetate microparticles:
adding 200kg of vitamin A acetate and 6kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; in addition, 100kg of gelatin, 400kg of sucrose, 284kg of corn starch and 10kg of silicon dioxide are uniformly mixed in a mixer according to a certain proportion to obtain powder, then the powder and the vitamin A oil are added into a ball mill according to a certain proportion to be ground and coated, so that the vitamin A oil and the wall material of the powder are effectively coated under the action of mechanical chemical force, and the vitamin A acetate particles are obtained through screening. Sampling the vitamin A acetate particles, carrying out mixed batch after the detection is qualified, and carrying out metal detection, packaging and warehousing after the detection is qualified.
Example 2: preparation of 40% vitamin a acetate microparticles:
adding 400kg of vitamin A acetate and 12kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; and mixing 94kg of gelatin, 300kg of sucrose, 184kg of corn starch and 10kg of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to perform grinding coating, so that the vitamin A oil and wall materials of the powder are effectively coated under the action of mechanical chemical force, obtaining vitamin A acetate particles through screening, sampling the vitamin A acetate particles, mixing the particles after the detection is qualified, and performing metal detection, packaging and warehousing after the detection is qualified.
For the vitamin A acetate particles prepared in examples 1-2, the appearance was pale yellow to tan powder. Through detection, 100% of vitamin A acetate particles can pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the Pb weight metal content is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
Comparative example 1:
adding 200kg of vitamin A acetate and 6kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; mixing 100kg gelatin, 400kg sucrose and pure water (90% -150% of solid mass) in a mixer according to a certain proportion, and heating for dissolving; adding vitamin A oil, mixed liquid and 284kg of corn starch and 10kg of silicon dioxide into a spray fluidized bed for spray granulation; the granularity is as follows: more than 99% passes through an analysis screen with a pore size of 0.84 mm.
Comparative example 2:
adding 400kg of vitamin A acetate and 12kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; mixing 94kg gelatin, 300kg sucrose and pure water (90% -150% of solid mass) in a mixer according to a certain proportion, and heating for dissolving; adding vitamin A oil, mixed liquid and 184kg of corn starch and 10kg of silicon dioxide into a spray fluidized bed for spray granulation; the granularity is as follows: more than 99% passes through an analysis screen with a pore size of 0.84 mm.
Example 3: the appearance, bioavailability, stability, etc. of the vitamin a acetate microparticles of examples 1-2 and comparative examples 1-2 were examined to obtain the following results:
compared with the conventional spray preparation method, the preparation method of the vitamin A acetate particles has the advantages that the bioavailability and stability of the vitamin A acetate particles are greatly improved, and the stability of the vitamin A acetate particles with 20 percent of content is optimal. Although the stability of the vitamin a acetate particles is reduced at 40%, the stability and bioavailability are also greatly improved compared to spray granulation.
Example 4: stability experiment of vitamin A acetate microparticle at 40% content-increasing BHT usage
Adding 400kg of vitamin A acetate and 20kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; and mixing 94kg of gelatin, 300kg of sucrose, 184kg of corn starch and 10kg of silicon dioxide uniformly in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to perform grinding coating, so that the vitamin A oil and wall materials of the powder are effectively coated under the action of mechanical chemical force, obtaining vitamin A acetate particles through screening, sampling the vitamin A acetate particles, mixing the particles after the detection is qualified, and performing metal detection, packaging and warehousing after the detection is qualified.
By increasing the consumption of BHT, the stability of the vitamin A acetate particles with 40% content can be enhanced, but the effective component retention rate can reach 90% -92% under the conditions of high temperature 60 ℃ and high humidity 90% +/-5% or strong illumination 6000 lx+/-1000 lx for 10 days. There is still a certain gap between the stability of 20% vitamin A acetate particles. It is therefore considered that the stability of the vitamin a acetate particles is not only related to the amount of antioxidants used, but also to other excipients. Therefore, the types and the dosage of other auxiliary materials are screened.
Example 5: stability test of vitamin A acetate microparticle at 40% content-change of other adjuvants
For other adjuvants, the screening range includes substituting gelatin with kappa-type (kappa) carrageenan, agar, and sodium alginate; and mixtures of these four gums at 1:1, 2:1, 3:1. Replacing sucrose with lactose, mannitol, and glucose; a mixture of the four sugar compounds in the ratio of 1:1, 2:1 and 3:1.
Through screening, it was found that gelatin was replaced with gelatin: kappa-type (kappa) carrageenan = 2:1; substitution of sucrose for lactose: mannitol = 3:1; when the BHT content is 20kg, the effective component retention rate can reach 94% -96% under conditions of high temperature 60 ℃, high humidity 90% + -5% or strong illumination 6000 lx+ -1000 lx for 10 days.
The most preferred embodiment is as follows:
adding 400kg of vitamin A acetate and 20kg of BHT into an oil dissolving kettle, heating under the protection of nitrogen, stirring and dissolving to obtain vitamin A oil; 94kg of gelatin were also added: kappa-form (kappa) carrageenan = 2:1 mixture, 300kg lactose: uniformly mixing a mannitol=3:1 mixture, 176kg of corn starch and 10kg of silicon dioxide in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to perform grinding coating, so that the vitamin A oil and powder wall materials are effectively coated under the action of mechanical chemical force, screening to obtain vitamin A acetate particles, sampling the vitamin A acetate particles, mixing the particles after the detection is qualified, and performing metal detection, packaging and warehousing after the detection is qualified. The prepared vitamin A acetate particles are light yellow to tan powder in appearance. Through detection, 100% of vitamin A acetate particles can pass through an analysis sieve with the aperture of 0.84mm, the moisture is less than or equal to 5%, the Pb weight metal content is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg. The stability data are shown below:
through screening and formula optimization, the stability of the vitamin A acetate particles is improved by 40 percent, and compared with the original formula, the stability of the vitamin A acetate particles is obviously improved. Basically realizes the stability similar to 20% of vitamin A acetate particles and has higher bioavailability.
The above description is a general description of the application. Variations in form and value may be substituted for the purpose of illustration and not limitation, as the terms are used herein, depending on the circumstances or actual requirements. Various changes and modifications may be made by one skilled in the art, and such equivalents are intended to fall within the scope of the application as defined in the following claims.
Claims (6)
1. A preparation method of high-content vitamin A acetate particles is characterized by comprising the following steps of: adding 300-500 parts by mass of vitamin A acetate and 15-40 parts by mass of antioxidant into a container, heating under the protection of non-oxygen gas, stirring and dissolving to obtain vitamin A oil; and 50-200 parts by mass of gelatin: kappa-type (kappa) carrageenan = 2:1 mixture, 200-800 parts by mass lactose: uniformly mixing a mannitol=3:1 mixture, 120-600 parts by mass of corn starch and 5-20 parts by mass of silicon dioxide in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to perform grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and sieving to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis sieve with a pore diameter of 0.84mm, the moisture is less than or equal to 5%, the weight metal content of Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0 mg/kg;
the non-oxygen gas is one or more of nitrogen, inert gas and carbon dioxide;
the antioxidant is 2, 6-di-tert-butyl-4-methylphenol (BHT).
2. The method of claim 1, further comprising the steps of inspecting and packaging, sampling the vitamin a acetate particles, mixing the particles after the particles are inspected to be qualified, inspecting the metals after the particles are inspected to be qualified, packaging, and warehousing.
3. The preparation method according to claim 1, wherein 400 parts by mass of vitamin a acetate and 20 parts by mass of an antioxidant are added into a container, and the mixture is heated and stirred to be dissolved under the protection of non-oxygen gas to obtain vitamin a oil; 94 parts by mass of gelatin: kappa-type (kappa) carrageenan = 2:1 mixture, 300 parts by mass lactose: uniformly mixing a mannitol=3:1 mixture, 176 parts by mass of corn starch and 10 parts by mass of silicon dioxide in a mixer according to a certain proportion to obtain powder, adding the powder and vitamin A oil into a ball mill according to a certain proportion to perform grinding coating, so that the vitamin A oil and powder wall materials are effectively coated, and screening to obtain vitamin A acetate particles, wherein more than 99% of the vitamin A acetate particles pass through an analysis screen with a pore diameter of 0.84mm, the moisture is less than or equal to 5%, the weight metal content calculated by Pb is less than or equal to 20mg/kg, and the total arsenic content is less than or equal to 2.0mg/kg.
4. A method of manufacture as claimed in any one of claims 1 to 3 wherein the vessel is an oil tank.
5. A method of preparation according to any one of claims 1 to 3, wherein more than 99.5% of the vitamin a acetate particles pass through an analysis screen having a pore size of 0.84 mm.
6. A method of preparation according to any one of claims 1 to 3, wherein 100% of the vitamin a acetate particles pass through an analytical sieve having a pore size of 0.84 mm.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE202004021155U1 (en) * | 2003-03-14 | 2007-02-15 | Basf Ag | Adsorbates for use in human or animal nutrition or cosmetics are produced by introducing material to be adsorbed together with stabilizer on to carrier |
| CN104186976A (en) * | 2014-08-11 | 2014-12-10 | 嘉兴天和诚生物科技有限公司 | Vitamin A acetate beadlet and production method thereof |
| CN110250521A (en) * | 2019-05-15 | 2019-09-20 | 万华化学集团股份有限公司 | A kind of preparation method of retinyl acetate microcapsules |
| CN113181157A (en) * | 2021-05-24 | 2021-07-30 | 万华化学集团股份有限公司 | Preparation method of vitamin A acetate micro-capsule |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE202004021155U1 (en) * | 2003-03-14 | 2007-02-15 | Basf Ag | Adsorbates for use in human or animal nutrition or cosmetics are produced by introducing material to be adsorbed together with stabilizer on to carrier |
| CN104186976A (en) * | 2014-08-11 | 2014-12-10 | 嘉兴天和诚生物科技有限公司 | Vitamin A acetate beadlet and production method thereof |
| CN110250521A (en) * | 2019-05-15 | 2019-09-20 | 万华化学集团股份有限公司 | A kind of preparation method of retinyl acetate microcapsules |
| CN113181157A (en) * | 2021-05-24 | 2021-07-30 | 万华化学集团股份有限公司 | Preparation method of vitamin A acetate micro-capsule |
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