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Allopregnanolone derivative self-emulsifying preparation and preparation method thereof

A technology of allopregnanolone and derivatives, applied in the field of medicine, can solve the problems of inconvenient use by medical staff, poor compliance of patients with allopregnanolone injection, complicated infusion methods, etc. The effect of long drug time and high bioavailability

Pending Publication Date: 2022-04-15
NANJING MINOVA PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Piespregnanolone injection produces stable and physiological concentration of piespregnanolone through intravenous injection to achieve the therapeutic effect, but it needs up to 60 hours of intravenous infusion, the infusion method is complicated, and professional treatment is required during the infusion. of healthcare workers to conduct continuous on-site monitoring and intervene as necessary
Leading to poor compliance of patients with pispregnanolone injection, it is extremely inconvenient for medical staff to use

Method used

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  • Allopregnanolone derivative self-emulsifying preparation and preparation method thereof
  • Allopregnanolone derivative self-emulsifying preparation and preparation method thereof
  • Allopregnanolone derivative self-emulsifying preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] Example 1. Self-emulsifying formulation of compound 2

[0088] The formulation is shown in Table 1 below, which is the self-emulsifying formulation formulation of Compound 2 in Table 1 below, and the composition details (mg / capsule and weight %) in Table 1 are based on a fill weight of approximately 500 mg per size 0 hard gelatin capsule. However, at self-emulsifying formulation amounts of less than about 100 mg / capsule, the formulation can be scaled for a smaller total fill weight allowing the use of smaller hard gelatin capsules (eg, size 1 or smaller if desired).

[0089] Table 1 compound 2 self-emulsifying formulation prescription

[0090]

[0091]

[0092] Preparation process: mix API with prescription amount with oil phase (such as castor oil, glyceryl monooleate or glycerol monolinoleate), emulsifier (such as polyoxyethylene (35) castor oil EL, polyoxyethylene (40) Hydrogenated castor oil (RH40), Tween 80 or Labrosal), and co-emulsifier (if any, such as et...

Embodiment 2

[0101] Embodiment 2. Solubility of each compound in different components

[0102] Take 10 g of different oil phases or hydrophilic surfactants and place them in 100 mL Erlenmeyer flasks with stoppers, add each compound to it one by one until insoluble, and record the corresponding dosage m, and visually measure the solubility S=m / 10g. In addition, shake in a constant temperature culture shaker at room temperature for 48 hours, take the supernatant after centrifugation, and use the HPLC method to detect the solubility. The results are shown in Table 2. In the following table 2, the values ​​expressed by the range of values ​​are visual solubility, and in the following table 2, the values ​​expressed by the specific values ​​are the solubility detected by HPLC.

[0103] Table 2 The saturation solubility of each compound in different solvents

[0104]

[0105] Each compound has good solubility in the oil phase and hydrophilic surfactants described in the present invention, an...

Embodiment 3

[0106] Example 3. Preferred self-emulsifying formulations of compounds according to the invention

[0107] See Table 3 below for prescription

[0108] Table 3 Preferred self-emulsifying formulations of compounds of the present invention

[0109]

[0110] Preparation process: mix the API of prescription amount with oil phase (such as castor oil or glycerol monolinoleate), emulsifier (such as polyoxyethylene (35) castor oil, polyoxyethylene (40) hydrogenated castor oil, Tween 80 or Labrosal, etc.), co-emulsifier (if any, such as ethanol, propylene glycol or PEG400, etc.), and stir fully in a magnetic stirrer at room temperature until the API is completely dissolved to obtain a clear oil solution, and then filled according to the amount of 500mg / granule in the capsule shell.

[0111] According to the self-emulsification efficiency evaluation experiment and preparation stability evaluation experiment method in Example 1, evaluate the self-emulsification efficiency and stabili...

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Abstract

The invention belongs to the field of medicines, and particularly relates to an allopregnanolone derivative self-emulsifying preparation and a preparation method thereof. The self-emulsifying preparation of the allopregnanolone derivative provided by the invention can completely dissolve the allopregnanolone derivative, is high in bioavailability and long in half-life period, can maintain the allopregnanolone with stable physiological concentration in vivo for a long time, and is suitable for oral administration. The self-emulsifying preparation of the allopregnanolone derivative comprises the following components in percentage by weight: (a) 5 to 25 percent of dissolved allopregnanolone derivative; (b) 45-80% by weight of an oil phase; (c) 10-50% by weight of at least one hydrophilic surfactant; and (d) 0-30% by weight of a co-emulsifier; the allopregnanolone derivative has a structure as shown in the following formula I, and R is alkyl containing 1-10 carbons.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a self-emulsifying preparation of an allopregnolone derivative and a preparation method thereof. Background technique [0002] Brexanolone, chemical name: (3α,5α)-3-hydroxy-pregn-20-one, structural formula as shown below, is a neuroactive steroid substance. In 2019, SAGE Therapeutics launched Pippregnanolone Injection in the United States under the trade name: Zulresso, and the listing indication is: adult postpartum depression (PPD). [0003] [0004] Pregnanolone and its derivatives are research hotspots in recent years, and a number of pharmaceutical companies are developing allopregnanolone derivatives. As early as 1986, it was pointed out that pippregnanolone is GABA A Positive modulator of the receptor, allopregnolone may be primarily associated with GABA A The combination of the α and β subunits of the receptor increases the opening frequency of the chloride ion c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/57A61K9/48A61K47/10A61K47/14A61K47/22A61K47/26A61K47/44A61P25/20A61P25/22A61P25/24
Inventor 姜伟化王琳吴刚刘飞张翠霞
Owner NANJING MINOVA PHARM CO LTD