Mixed glue bundle pharmaceutical preparations produced in combination use of multiple surfactant and processes for their preparation

A surfactant, mixed micelle technology, applied in the field of medicine, can solve the problems of unsafe and inconvenient clinical use, hemolysis and allergic reactions, large release of histamine, etc., to achieve convenient clinical medication, strong dilution stability, Toxicity reduction effect

Inactive Publication Date: 2008-03-12
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the clinical research, it was found that the preparation had relatively serious hemolysis and allergic reactions, and it was necessary to use anti-allergic drugs in advance to prevent it before taking the medicine, which was neither safe nor convenient for clinical use
Studies have shown that Tween 80 may be one of the main reasons for the toxic and side effects of docetaxel preparations[U.Vanhoefer, S.Cao, A.Harstrick, et al. the multidrugresistance protein (MRP), Ann.Oncol.8 (1997) 1221-1228. [11] S.B.Kaye, Taxoids, Eur.J.Cancer 31A (5) (1995) 824-826], histamine release is extremely large

Method used

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  • Mixed glue bundle pharmaceutical preparations produced in combination use of multiple surfactant and processes for their preparation
  • Mixed glue bundle pharmaceutical preparations produced in combination use of multiple surfactant and processes for their preparation
  • Mixed glue bundle pharmaceutical preparations produced in combination use of multiple surfactant and processes for their preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1 Solubilization of docetaxel by HS15-EPC mixed micelles

[0043] HS15 (see Figure 1 for structure) and phospholipids form mixed micelles. The main component of lecithin is phosphatidylcholine (PC, the structure is shown in Figure 2). The two acyl chains of PC increase the hydrophobicity inside the micelles, which can increase the affinity for fat-soluble drugs, and its flexibility is good for accommodating drug molecules and forming a stable combination that favors van der Waals forces. In addition, the intervention of PC makes the structure of mixed micelles slightly swell, and the volume is larger than simple micelles, which can hold more fat-soluble drug molecules [Chen Jing, Tu Xide, Huang Feiyun, etc. New adjuvant for injections- --Bile salt / lecithin mixed micellar system. Progress in Pharmacy, 2001, 25(4): 227-230].

[0044] Prescription: 200ml

[0045] HS15 30g

[0046] EPC 7g

[0047] Doc 1g

[0048] Cit a 0.5g

[0049] Preparation: Precisely weigh the pres...

Embodiment 2

[0058] Example 2 Solubilization of docetaxel by HS15-S100 mixed micelles

[0059] Prescription: 200ml

[0060] HS15 30g

[0061] S100 7g

[0062] Doc 1g

[0063] Cit a 0.25g

[0064] Preparation: Replace EPC with S100, and the rest is the same as in Example 1.

[0065] Stability: The stability of the prescription and its dilution (the drug concentration is 1mg / ml) is shown in Table 3-4.

[0066] Table 3 Preparation stability test results (room temperature crystallization situation)

[0067] 0 o'clock

[0068] Table 4 Dilution stability test results (crystallizing at room temperature)

[0069] 2 hours

[0070] Conclusion: The mixed micelle preparation has good stability, and no crystals are observed within 3 months; the difference between the dilution with normal saline and glucose injection is large, and the glucose injection dilution group has partial analysis of crystals after 16 hours, while the normal saline In the dilution group, no crystals were seen...

Embodiment 3

[0071] Example 3 Solubilization of docetaxel by HS15-SPC97 mixed micelles

[0072] Prescription: 200ml

[0073] HS15 30g

[0074] SPC97 10g

[0075] Doc 1g

[0076] Cit a 0.05g

[0077] Preparation: Replace EPC with SPC97, adjust the dosage appropriately according to the prescription ratio, and the rest is the same as in Example 1.

[0078] Stability: See Table 5-6 for the results of the prescription and its stability after dilution.

[0079] Table 5 Preparation stability test results (room temperature crystallization situation)

[0080] 1 hour

[0081] Table.6 Crystallization time after dilution of the formula (room temperature crystallization situation)

[0082] 2 hours

[0083] Conclusion: The mixed micelle preparation has good stability, and no crystals are observed within one month; no crystals are seen 58 hours after dilution, which is beneficial for clinical administration. Its particle size is less than 100nm.

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Abstract

The present invention relates to a mixed micelle medicine preparation and a preparation method, which is prepared by the combination of various kinds of surface acting agents. The mixed micelle consists of the polyethylene glycol-12-hydroxy stearate and the other surface acting agents of one kind or various kinds. The other surface acting agents comprise phospholipid, VE Macrogol succinate, Macrogol-VE-carbonate and Macrogol-VE-succinate. In addition, the mixed micelle also comprises drugs, solvent, a stabilizer with or without other components and a PH conditioner. The amount of the polyethylene glycol-12-hydroxy stearate in the prescription is 4 percentage to 40 percentage, W / V: the amount of the phospholipid is 0 percentage to 30 percentage, W / V: the amount of the activator is 0 percentage to 30 percentage, W / V: the amount of the drug is 0.001 percentage to 10 percentage, W / V: the amount of the solvent is 0 percentage to 90 percentage, W / V. The medicine comprises the hydrophobicity drug and the lip solubility drug, but the medicine is not restricted by the both kinds of drugs. The present invention has the following advantages. Firstly, the preparation has good dilution stability, which can improve the defect in the present preparation and can meet the demanding for clinical drug administration. Secondly, the toxicity is low and the chemical stability is excellent.

Description

Technical field: [0001] The invention relates to the technical field of medicine, and to be precise, it is a mixed micelle pharmaceutical preparation prepared by the combined use of multiple surfactants and a preparation method thereof. technical background: [0002] Among the medicinal active substances, there are a large part of fat-soluble drugs that are difficult to dissolve in water, which brings a lot of inconvenience to the preparation process and clinical application, and also brings many adverse effects on the effectiveness of the drug, and it is even difficult to prepare a reasonable amount. preparation. In order to solve such problems, one of the more commonly used methods is to solubilize drugs with surfactants. [0003] Surfactant refers to a substance that can significantly reduce the surface tension of a liquid at a relatively low concentration. The structural characteristics of surfactant molecules are composed of polar hydrophilic groups and non-polar hydrophobic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/34A61K45/06A61K47/14
Inventor 邓意辉石莉卢懿董晓辉徐缓
Owner SHENYANG PHARMA UNIVERSITY
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