Popular keyword search:
Search
Your location:Home > News centre > Company News

NEWS

HOT NEWS

Introduction to the source and application of cholesterol

Time:2020-09-30

Views:418

What is the source of the common injection-grade cholesterol excipients in liposomes? What application does it have? AVT editor will give you a good introduction.


Introduction to the source and application of cholesterol -AVT (Shanghai) Pharmaceutical Tech Co., Ltd


What kind of excipient product is high purity injection grade cholesterol CHO-HP?

1 Chinese name: Cholesterol (for injection)

2 Product name: CHO-HP

3 Chemical name: Cholester-5-en-3β-ol

4 English chemical name: Cholest-5-en-3β-ol

5 Molecular formula: C27H46O

6 Manufacturer: Made in Japan

7 CAS Number: 57-88-5

8 DMF number: 24780

9 EINECS No.: 200-353-2

11 Registration number: F20170000106

12 Level: medicinal injection level

13 Executive standards: USP, EP, CP

14 Uses: liposome membrane material, emulsifier

15 Molecular weight: 386.7

16 Storage conditions: room temperature

17 Matters needing attention: avoid strong acid, strong alkali, strong oxidizing substance

What are the characteristics of cholesterol?

CHO-HP is a high-purity injection grade pharmaceutical excipient produced under cGMP conditions, DMF number: 024780, import registration application number: JXFL1100010. It is the only cholesterol injection grade excipient in China. Different from the domestically used animal tissue extraction method to produce cholesterol, CHO-HP is made from wool grease and semi-synthetic method, with high purity (>99%), and will not have the problem of virus contamination of animal tissues. Many marketed liposome products have been used in the medium and long term.

CHO-HP is a white powdery solid with good stability at room temperature, but it is sensitive to light. Therefore, it should be protected from light, sealed and stored properly. The validity period can reach 5 years. Easily soluble in chloroform (1g/4.5ml), soluble in ether (1g/2.8ml), slightly soluble in acetone, ethyl acetate or petroleum ether, slightly soluble in ethanol, insoluble in water (0.2mg/ 100ml).

Source of cholesterol

The medicinal cholesterol CHO-HP is in great demand every year. However, because it is a multi-chiral substance and is difficult to synthesize, it is currently obtained by two methods: animal tissue extraction and lanolin extraction.

Animal tissue extraction

The animal tissue extraction method uses fresh animal viscera, bone marrow and brain as raw materials. The process is acetone extraction → ethanol purification → sulfuric acid hydrolysis → low temperature crystallization → activated carbon decolorization → multiple crystallization. The process is simple and feasible. It is currently the main domestic cholesterol production process. However, it is easily restricted by the supply of raw materials and may leave the product with pathogenic genes.

Lanolin extraction

Wool grease is a by-product of the wool industry. The cholesterol content in wool grease is high, about 10-15%, and the finished products are cheap and rich in sources, high in stability and safety. Most cholesterol abroad is made of lanolin as raw material. However, most of the cholesterol in lanolin is combined with lanolin acid in the form of esters, and there are many cholesterol analogs, so it is very technically demanding to obtain pure products. Cholesterol is freed by the saponification process, and the cholesterol obtained by saponification also contains a large amount of dehydrocholesterol, dihydrocholesterol and the like. Due to the similar molecular structure and similar properties, it brings difficulties to separation and becomes a technological difficulty and key point. However, with the emphasis on drug safety, cholesterol derived from lanolin will surely gradually replace cholesterol derived from animal organs.

Application of Cholesterol in Pharmacy

First of all, cholesterol is the starting material for the synthesis of hormones such as vitamin D, so it can be used as a raw material.

Secondly, cholesterol can be used as a pharmaceutical excipient, used as an emulsifier or liposome membrane component, and the route of administration includes external application, oral administration, or injection. The Chinese Pharmacopoeia, European Pharmacopoeia, American Pharmacopoeia, Japanese Pharmacopoeia, etc. all contain various levels and sources of cholesterol.

Source 1. It is necessary to indicate the specific source, such as bovine brain, spinal cord, lanolin or eggs

Content: Cholesterol not less than 95.0%

CHOLESTEROL, P1873-1874, European pharmacopoeia 8.0

Source 2: It is derived from animal organ extraction and purification

Content: Cholesterol is not less than 95.0%

Category: pharmaceutical excipients, emulsifiers and ointment bases, etc.

Cholesterol, P540, Chinese Pharmacopoeia 2015 edition four

Source 3: Lanolin

Content: Cholesterol 99.0-101.0%

CHOLESTEROL FOR PARENTERAL USE, P1874-1876, European pharmacopoeia 8.0

Cholesterol for injection is an important excipient in the preparation of liposomes. Phospholipids are the material basis of the bilayer. In theory, liposomes can be formed as long as there are phospholipids. However, we know that the long acyl chains of phospholipids have very strong fluidity, just like the water plants in the waves, which are always in a state of swing. Although this fluidity gives the liposomes good flexibility and deformability, it also makes the membrane very permeable. This means that the exchange of substances inside and outside the liposome becomes very easy. When liposomes are used to encapsulate drugs, this excessively high permeability will make the drugs easily "escape" from the internal aqueous phase, and the drug loading will decrease. Adding a small amount of cholesterol to phospholipids to regulate membrane fluidity is a skill that people learn from nature. There is a large amount of cholesterol in biofilms. In addition to assuming certain physiological functions, it is more important to participate in the structural functions of biofilms. If the neatly arranged phospholipid molecules that make up the bilayer are described as a fence, cholesterol is like a rope that binds the fence, making the binding between the phospholipid molecules tighter and stronger, and making the liposomes more stable. Facts have proved that adding 30-50% cholesterol when preparing liposomes can greatly improve the drug loading and stability of liposomes.

The amount of cholesterol in some liposomal drugs


Drug trade name

common name

Cholesterol dosage

DOXIL

Doxorubicin Hydrochloride Liposome Injection

3.19 mg/mL

AmBi some

Amphotericin B liposome lyophilized powder

52mg/bottle

EXPAREL

Bupivacaine Multivesicular Liposome Suspension

8.2mg/ml

0niivyde

Irinotecan Liposome Injection

2.22mg/ml


在线咨询
Service
Landline
021-58876118
Hotline
13916637505