A：1、The hemolysis test and cytotoxicity test proved that there was no statistical difference in all data points between the Zhiyuan product and the original product.
2、Through UV absorbance comparative testing, the impurities in Zhiyuan products have reached the international original research level and are significantly better than those in the domestic industry.
3、Through comparative testing of the inclusion efficiency of posaconazole and voriconazole, it was found that Zhiyuan’s product has equivalent inclusion capabilities to the original research product and has good stability.

A：Zhiyuan’s Sulfobutyl beta Cyclodextrin Sodium and Simcere Pharmaceuticals made a joint application and have now passed the on-site review. CDE No: F20190000285.

A：Preparations include: posaconazole injection, voriconazole injection, remdesivir injection, carfilzomib injection, ziprasidone injection, aripiprazole injection, amiodarone injection, etc.

A：voriconazole
Vfend
ziprasidone，Product name：Geodon
posaconazole，Product name：Noxafil

A：Commonly used poorly soluble drugs include: voriconazole, carfilzomib, ziprasidone, maropitant (animal medicine), aripiprazole, posaconazole,
Carbamazepine, melphalan, delafloxacin, mebendazole, topiramate, omeprazole, clopidogrel, docetaxel, sofosbuvir,
Ziprasidone mesylate, chlorambucil, meloxicam, allopregnanolone, and several other nitrogen-containing API bases are in various clinical stages.

A：The higher the pH, the better, but the quality standard of our products is 4.0-6.8, so it can be guaranteed to be around 6.5.

A：A、When the pH is less than 5.5, it will tend to decrease in a short period of time (within about 48 hours) and then increase.
B. When the pH is greater than 5.5, the pH of the solution increases with the placement time and tends to be neutral.

A：For the detection of bacterial endotoxins in any product, refer to the General Chapter 1143 of the 2020 edition of the Chinese Pharmacopoeia or USP-NF2021<85>. First conduct methodological verification, use the verified method to test the corresponding sample to see if it meets the regulations, verify and test. The cycle is about 7-15 days. The same goes for the inspection of microbial limits, and the cycle of verification and testing is about 20-30 days.

A: The difference in indicators between oral grade and injection grade of hydroxypropyl beta cyclodextrin is reflected in two points:
The first is that injection-grade hydroxypropyl beta cyclodextrin increases the control of bacterial endotoxins, requiring bacterial endotoxins to be less than 0.01EU/mg.
The second is that injection-grade hydroxypropyl beta-cyclodextrin has a higher requirement for beta-cyclodextrin residue index: <0.1%.

A: Preparations include butylphthalide injection, itraconazole injection, letermovir injection, telavancin injection, etc.

A: 1. The Arabic numerals in the name of hydroxypropyl beta cyclodextrin usually indicate the modification position.
2. Cyclodextrin can be substituted at positions 2, 3, and 6 of the sugar unit. The 2-position substitution of commercially available hydroxypropyl beta cyclodextrin accounts for about 50-60%. 2-Hydroxypropyl beta-cyclodextrin refers to hydroxypropyl beta-cyclodextrin that is completely substituted with 2-position cyclodextrin. It is difficult to produce and is generally only used for scientific research.
3. The other hydroxypropyl group has two isomers: (2-hydroxypropyl) and (3-hydroxypropyl). Commercially available hydroxypropyl beta-cyclodextrin is (2-hydroxypropyl) beta-cyclodextrin, where 2 represents the 2-position of the propyl group rather than the 2-position of the cyclodextrin.

A: The Cas number is unique like an ID number. However, hydroxypropyl beta cyclodextrin itself is a mixture with multiple isomers. Scifinder, the official Cas organization, had earlier given hydroxypropyl beta cyclodextrin two CAS numbers. Now the two numbers have been merged and it is recommended to delete 94035-02-6. 128446-35-5 is used in the Chinese Pharmacopoeia, and 128446-35-5 is also used in the United States Pharmacopoeia.

A: First, through UV absorbance comparative testing, Zhiyuan products have the lowest impurity content, which is obviously due to the level of the same industry at home and abroad.
Second, through comparative testing of the inclusion efficiency of 6-methylcoumarin, the products of Zhiyuan Biotechnology Chinese Pharmacopoeia and European and American Pharmacopoeia have higher performance than similar products.
Stronger package capabilities and higher package efficiency.

A: 1. Because a beta cyclodextrin molecule is composed of 7 glucose unit molecules, the relationship between the average degree of substitution and the molar degree of substitution is 7 times: average degree of substitution = molar degree of substitution * 7.
2. The index indicating the degree of substitution in the Chinese Pharmacopoeia is the hydroxypropyloxy group content, while in the European and American Pharmacopoeia it is the molar degree of substitution. The formula conversion relationship is as follows:
n=1135A/(75-58A)
n is the average degree of substitution, A is the hydroxypropoxy group content

A: Generally, there are three degrees of substitution. One is 4.5-5.0 (can also be understood as ≤5.0, complying with ChP, USP, EP); one is 5.0-6.0 (compliant with USP); the others are customized products.

A: 1. It has not been included in the food additive catalog in China and cannot be used in food according to regulations (beta cyclodextrin, alpha cyclodextrin, and gamma cyclodextrin have been included in the food additive catalog).
2. Abroad, the food supplements provided by the Food and Agriculture Organization of the United Nations only contain three parent cyclodextrins: alpha, beta and gamma.

A: 1. The degree of substitution is 4.2, solubility in water: >100g/(100g water, 20℃)
2. The degree of substitution is 5.3, solubility in water: >115g/(100g water, 20℃)

A: 1. It is an enterprise standard and is mainly used in veterinary medicine, industry, daily chemical and other industries.
2. Popular science: The GMP we are talking about refers to “Good Manufacturing Practice for Drugs”; the reference for the production of veterinary drugs is “GMP for Veterinary Drugs” and “Good Manufacturing Practice for Veterinary Drugs”;
For industrial purposes, please refer to the management system of IS09001.

A: 1. There is a requirement for bacterial endotoxin.
2. There are requirements for bacterial endotoxin, and the beta-cyclodextrin residue is less than 0.1%. The conductivity is between 30-50μs/cm.

A: SBECD and HPBCD have different production costs. Regarding the types of inclusion drugs, HPCD is generally positioned as a central nervous system drug; SBECD is generally an antifungal drug. For inclusion drug types, please refer to the following table:
Hydroxypropyl beta cyclodextrin: used as enhanced biocompatibility, complexing agent, solubilizer, penetrant, stabilizer, diluent for tablets or capsules, viscosity increaser, water activity reduction, etc. Injections, oral solid preparations, ophthalmic preparations, intranasal preparations, inhalants and external preparations can also be used as carriers for lipophilic targeted drugs and as protectants and stabilizers for proteins.

Sulfobutyl beta cyclodextrin sodium: increases drug solubility and improves bioavailability; increases drug stability; relieves and improves local irritation; regulates drug release; enhances drug absorption and utilization. It is used in injection preparations, oral preparations, intranasal preparations and ophthalmic preparations.

A: 1. No.
2. Heavy metals in hydroxypropyl betacyclodextrin and sulfobutylbetacyclodextrin sodium. We have formulated elemental analysis reports based on the Q3D guidelines in ICH, and the content of each heavy metal element can be effectively controlled. Specific data can be found in the elemental analysis report.
3. For the detection of heavy metal content in other products, we have controlled it with reference to the Four General Chapters 0821 of the 2020 edition of the Chinese Pharmacopoeia.

Answer: For heavy metals in hydroxypropyl betacyclodextrin and sulfobutylbetacyclodextrin sodium, we have formulated elemental analysis reports based on the Q3D guidelines in ICH, and the content of each heavy metal element can be effectively controlled. Specific data can be found in the elemental analysis report.

A: 1. The validity period of cyclodextrin excipients refers to the retest period, and it does not mean that they will be broken upon expiration.
2. After being made into API, cyclodextrin has changed. You cannot simply look at cyclodextrin. It is a new substance at this time and is processed by cyclodextrin, API, etc.
Become. Its stability cannot be determined solely by the shelf life of its ingredients.
For example: Generally, the raw and excipients of API produced by factories will have a retest period of about 1 year, but the validity period of the produced API is calculated from the time of production.
The validity period of the preparation should be calculated from the beginning of preparation production, regardless of the validity period of the raw materials.

A: From the date of production, the shelf life of hydroxypropyl beta cyclodextrin is 2 years when stored according to specified storage conditions. Storage beyond the expiry date on the label does not necessarily mean that the product is no longer usable. In this case, however, for quality assurance reasons, the user must check to confirm the performance required for the intended use.

A: All pharmacopoeias, including the Chinese Pharmacopoeia and the United States Pharmacopoeia, do not stipulate the measurement of purity. There is currently no detection method, and there is no standard substance for liquid phase detection, so purity cannot be detected. Hydroxypropyl beta cyclodextrin itself is a mixture with an average degree of substitution of 2.8-10.5. The degree of substitution may be 3 or 5. Can we generally calculate it based on other indicators tested?
(100-ignition residue-beta content %-chloride)/(100-moisture %)

2. In the Chinese Pharmacopoeia, the hydroxypropoxy group content (19.6%~26.3%) is measured, and the average degree of substitution (3.5-5.0) is converted using a formula.

Answer: Formula: n=1135A/(75-58A)
n is the average degree of substitution, A is the hydroxypropoxy group content
The hydroxypropoxy group content is the mass content of hydroxypropyl groups in all products. It can be calculated by the total degree of substitution: hydroxypropoxy group content = 75n/(58n+1135) n is the average degree of substitution
3. Overseas, the molar degree of substitution is the molar degree of substitution *7 = average degree of substitution

A: 1. Impurity residues are different: technical grade impurities have more residues, such as sodium chloride, propylene glycol, etc.
2. The average degree of substitution is different: technical grade substitution degree 4-6, pharmaceutical grade substitution degree 3.5-5
3. The control of indicators such as microorganisms is different: the technical level does not control microbial endotoxins, etc.
4. The effective content is different: the effective content of technical grade is lower than 96%, while the content of oral grade is more than 98%.
5.CP pharmaceutical grade has no conductivity, no chloride, and is an indicator of hydroxypropoxyl content and no degree of substitution.

Answer: 1. The output is the largest in the industry, 2,000 tons per year.
2. The degree of substitution meets the customer’s purpose and is mainly used as a dispersant.
3. Best price
4. Lower cost 50% aqueous solution can be provided

A: The methyl beta cyclodextrin produced by Zhiyuan has been registered with China CDE, and the registration number is F20210000272. Since methyl beta cyclodextrin has not entered the pharmacopoeia at home and abroad, the product testing standards are corporate standards, but microbial indicators are controlled during the production process. Relevant companies are welcome to submit joint applications.

A:
A. Calculation of the molecular weight of methyl beta cyclodextrin: 1135+14n (n is the degree of substitution)
B. The solubility of methyl beta cyclodextrin in water is >100g/(100g water, 20℃), that is, 50% of the aqueous solution is clear.
C. The 50% aqueous solution is clear and colored.
D. The conductivity is similar to that of hydroxypropyl beta cyclodextrin. Theoretically it can reach about 10μs/cm, but the cost will be greatly increased. If customer service has requirements, you can refer to the USP standard of hydroxypropyl beta cyclodextrin ≤ 200 μS/cm.
E. Methyl beta cyclodextrin refers to substitution at positions 2, 3, and 6. If all positions 2, 3, and 6 are substituted, the degree of substitution is 21.
F. 2,6-dimethyl beta cyclodextrin refers to substitution at the 2,6 position, and its degree of substitution is 14.
G. The packaging is medicinal low-density polyethylene bags.
H. Methyl beta-cyclodextrin has high surface activity, and is a fat-soluble cyclodextrin with good skin permeability, which is beneficial to bringing active ingredients into the skin. Therefore, it is more effective than hydroxypropyl beta cyclodextrin in cosmetics. Please see the literature for more uses.
I. The existing vaccine pretreatment uses 2,6-dimethyl beta cyclodextrin.

A: Oil-soluble cyclodextrins include highly substituted methyl cyclodextrin, acetyl cyclodextrin (not done yet), and fatty acyl cyclodextrin (not done yet). Existing cyclodextrins recommend highly substituted methyl cyclodextrin. (If it can be registered with the Public Security Bureau to use acetic anhydride, acetyl cyclodextrin can be produced.)

A: The current application of methyl cyclodextrin in the market is that it is used in paints as a thickening agent control agent. That is, when the paint needs to be thickened, it can release the thickener and adjust the paint viscosity. Another use is in the vaccine production process, used to solubilize cholesterol substances to help microbial growth. (This paragraph is only methyl. Methyl cyclodextrin is soluble in some organic solvents and water-soluble. It is not a typical oil-soluble cyclodextrin)
Application in the literature: Oil-soluble cyclodextrin is used in combination with other cyclodextrins to control the release of drugs at designated sites.

A: 1. Domestic exclusive technology is a new product developed by our company relying on Shandong University;
2. The largest domestic output;
3. A wide range of substitution degrees means a wide range of applications. There are products with an average degree of substitution above 12, and products with an average degree of substitution below 12;
4. Able to control endotoxin and other impurity residues, and meet strict requirements for drugs, vaccines, cosmetics, etc.;
5. Priority is given to filing in CDE, and the filing materials are complete.

A: Highly substituted methyl cyclodextrin can be dissolved in organic solvents such as chloroform and tetrahydrofuran, but is insoluble in very weakly polar organic solvents such as petroleum ether, cyclohexane, and benzene.

A: 1. It is used in the production of eye drops abroad and has marketed products.
2. Hydroxypropyl gamma cyclodextrin has a larger cavity and is suitable for inclusion of macromolecular substances. It has higher solubility and stronger resistance to crystallization and precipitation.
3. Hydroxypropyl gamma cyclodextrin microbial and endotoxin control: Like hydroxypropyl beta cyclodextrin, sterility cannot be achieved under existing conditions.
4. Hydroxypropyl gamma cyclodextrin Calculate the average degree of substitution 75n/(58n+1297)=hydroxypropoxy group content

Answer: 75n=(58n+1297)*25.4%
75n=58n*25.4%+1297*25.4%
75n=58n*25.4%+1297*25.4%
75n=14.73n+329.44
n=5.47
The molecular weight of hydroxypropyl gamma cyclodextrin is 58n+1297=58*5.47+1297=1614.26

A: The hydroxypropyl gamma cyclodextrin produced by Chiyuan Biotechnology is currently an enterprise standard, and microorganisms and bacterial endotoxins are controlled during the production process. Currently, eye medications are widely used.

A: 1. Domestic exclusive technology is a new product developed by our company relying on Shandong University;
2. The largest domestic output;
3. Able to control endotoxin and other impurity residues, and meet strict requirements for drugs, vaccines, cosmetics, etc.;

A: Alpha cyclodextrin, beta cyclodextrin, and gamma cyclodextrin are the three commonly used basic cyclodextrins, and their raw materials are tapioca starch or corn starch. The difference is reflected in the following two points:
First, the diameter of the cyclodextrin cavity is different;
Second, the solubility of cyclodextrin in water is different.