CN101732255A - Flurbiprofen liposome and preparation method thereof - Google Patents

Abstract

The invention relates to a flurbiprofen liposome and a preparation method thereof. First weigh 1-10 parts of cholesterol, 5-40 parts of egg yolk lecithin, 2-50 parts of flurbiprofen and 1-10 parts of vitamin C by weight, and dissolve them with chloroform/methanol (mass ratio 4:1) , mix evenly to obtain a mixed solution, then place the above solution in a rotary evaporator, distill off chloroform and methanol under reduced pressure to obtain a lipid film, then add a phosphate buffer solution with a pH of 6 to 8 into the lipid film, Rotate on a rotary evaporator in a warm bath at 20-60° C. for 1-4 hours, ultrasonicate in a water bath for 5-30 minutes, and pass through a filter membrane of 0.22-0.45 μm to prepare flurbiprofen liposomes. The flurbiprofen liposome prepared by the invention has good stability, targeting and slow-release performance, can reduce the dosage, reduce the toxic and side effects of the drug, is suitable for both transdermal administration and oral administration, and can be widely used for preparation Oral liquid, aerosol, spray, ophthalmic or topical liposome dosage forms.

Description

A kind of flurbiprofen liposome and preparation method thereof

technical field

The invention relates to a flurbiprofen liposome and a preparation method thereof. It belongs to the technical field of pharmaceutical preparations.

Background technique

Flurbiprofen is one of the excellent varieties of non-steroidal anti-inflammatory analgesics, mainly used for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, traumatic pain and other pains. Flurbiprofen acts as an anti-inflammatory and analgesic by inhibiting the activity of prostaglandin synthase cyclooxygenase. The drug is effective orally and well tolerated, and long-term use neither promotes nor inhibits its own metabolism. Although flurbiprofen has unique anti-inflammatory and analgesic effects clinically, flurbiprofen is a lipophilic drug with low solubility in water, resulting in low oral bioavailability and serious gastrointestinal and central nervous system damage. Systemic adverse reactions. At present, most of the reports about flurbiprofen dosage forms are limited to the transdermal administration method of flurbiprofen, such as "flurbiprofen cataplasm and its preparation" (Chinese invention patent application number: 03116441.2, publication number : CN144353A) and "external patch containing flurbiprofen" (Chinese invention patent application number: 200580048135.4, publication number: CN101119716A). Liposomes are spherical closed vesicles formed by phospholipids dispersed in water. The substances that constitute the lipid bilayer (carrier) are mainly phospholipids (lecithin, cephalin, soybean lecithin) and cholesterol, etc., each of which can encapsulate drugs, and because of its molecular structure has both hydrophilic groups and With hydrophobic groups, water-soluble drugs are encapsulated in the interlayer of hydrophilic groups of vesicles, while fat-soluble drugs are dispersed in the interlayer of hydrophobic groups of vesicles. As a drug carrier, liposome is suitable for both transdermal and oral administration methods. Moreover, liposomes are non-toxic or have little toxic and side effects to the body, and their liposome bilayers have greater similarity and tissue compatibility with biological membranes, so they are easily absorbed by tissues and improve the bioavailability of drugs.

Contents of the invention

The object of the present invention is to provide a kind of composition of flurbiprofen liposome, the further object of the present invention is to disclose the preparation method of this flurbiprofen liposome. The flurbiprofen liposome prepared by the present invention is not only suitable for transdermal administration, but also suitable for oral administration. It is non-toxic or has little toxic and side effects to the body, and its liposome bilayer has greater similarity to biological membranes. As well as tissue compatibility, it is easy to be absorbed by tissues and improves the bioavailability of drugs.

In order to achieve the above object, the present invention adopts following technical scheme:

Flurbiprofen liposome of the present invention is made up of following parts by weight:

Cholesterol 1 to 10 servings

Flurbiprofen 2～50 parts

Egg yolk lecithin 5-40 parts

Vitamin C 1-10 servings

The preparation method of flurbiprofen liposome provided by the invention is as follows:

First weigh 1-10 parts of cholesterol, 5-40 parts of egg yolk lecithin, 2-50 parts of flurbiprofen and 1-10 parts of vitamin C by weight, then dissolve them with chloroform/methanol, and mix them evenly to obtain a mixed solution, the amount of chloroform/methanol is 2000 to 20000 times that of cholesterol, and then the above mixed solution is placed in a rotary evaporator, and the chloroform and methanol are removed by distillation under reduced pressure to obtain a lipid film, and then the pH is 6 to 8 Phosphate buffer solution is added to the lipid film, rotated on a rotary evaporator in a warm bath at 20-60°C for 1-4 hours, and finally ultrasonicated in a water bath for 5-30 minutes, and passed through a filter membrane of 0.22-0.45 μm to obtain flurbiprofen lipid plastid;

The aforementioned chloroform/methanol is chloroform:methanol=4:1 mass ratio.

The present invention has the following advantages:

1. The preparation method of the present invention is simple and easy to operate, the drug loss is small in the preparation process, and the raw material egg yolk lecithin has good biocompatibility and biodegradability.

2. Antioxidant vitamin C is added to the medicine of the present invention to improve the stability of liposomes and avoid the toxic and side effects caused by the peroxidation of phospholipids in vivo and in vitro.

3. Flurbiprofen is a hydrophobic drug, which is located in the hydrophobic region of the liposome bilayer lipid membrane. Adding egg yolk lecithin to flurbiprofen increases the order of lecithin molecular arrangement, thereby reducing the Fluidity of bilayer lipid membranes improves stability of flurbiprofen liposomes.

4. The flurbiprofen liposome prepared by the present invention is not only suitable for transdermal administration, but also suitable for oral administration. It is non-toxic or has little toxic and side effects to the body. Sexuality and tissue compatibility, so that it is easy to be absorbed by the tissue, and the bioavailability of the drug is improved.

5. The flurbiprofen liposome of the present invention has a wide range of uses and can be used in oral liquid, aerosol, spray, ophthalmic or external liposome dosage forms.

Detailed ways

Example 1

Weigh 6.0 mg of flurbiprofen, 15.0 mg of egg yolk lecithin, 3.0 mg of cholesterol, and 3.0 mg of vitamin C, dissolve them with 6.0 g of chloroform/methanol (mass ratio 4:1), and mix them uniformly to obtain a solution. The above solution was placed in a rotary evaporator, and chloroform and methanol were distilled off under reduced pressure to obtain a lipid film. Phosphate buffer solution with a pH of 6 was added to the lipid film, rotated on a rotary evaporator in a warm bath at 20°C for 4 hours, ultrasonicated in a water bath for 5 minutes, and passed through a 0.22 μm filter membrane to prepare flurbiprofen liposomes. The above raw materials are all commercially available.

Example 2

Weigh 6.0 mg of flurbiprofen, 15.0 mg of egg yolk lecithin, 30.0 mg of cholesterol, and 3.0 mg of vitamin C, dissolve them in 60 g of chloroform/methanol (mass ratio 4:1), and mix well. The above solution was placed in a rotary evaporator, and chloroform and methanol were distilled off under reduced pressure to obtain a lipid film. A phosphate buffer solution with a pH of 7 was added to a lipid film flask, rotated on a rotary evaporator in a 60° C. temperature bath for 1 h, ultrasonicated in a water bath for 30 min, and passed through a 0.45 μm filter membrane to prepare flurbiprofen liposomes.

Example 3

Weigh 30.0 mg of flurbiprofen, 50.8 mg of egg yolk lecithin, 6.0 mg of cholesterol, and 6.0 mg of vitamin C, dissolve them in 6.0 g of chloroform/methanol (mass ratio 4:1), and mix well. The above solution was placed in a rotary evaporator, and chloroform and methanol were distilled off under reduced pressure to obtain a lipid film. Phosphate buffer solution with a pH of 7 was added to a lipid film flask, rotated in a 30° C. temperature bath on a rotary evaporator for 3 h, ultrasonicated in a water bath for 15 min, and passed through a 0.45 μm filter membrane to prepare flurbiprofen liposomes.

Example 4

Weigh 64.0 mg flurbiprofen, 25.4 mg egg yolk lecithin, 15.0 mg cholesterol, 15.0 mg vitamin C, dissolve them with 30 g chloroform/methanol (mass ratio 4:1), and mix well. The above solution was placed in a rotary evaporator, and chloroform and methanol were distilled off under reduced pressure to obtain a lipid film. Phosphate buffer solution with a pH of 8 was added to the lipid film flask, rotated in a 50° C. temperature bath on a rotary evaporator for 2 h, ultrasonicated in a water bath for 25 min, and passed through a 0.22 μm filter membrane to prepare flurbiprofen liposomes.

Example 5

Weigh 150.0 mg flurbiprofen, 120.0 mg egg yolk lecithin, 3.0 mg cholesterol, and 30.0 mg vitamin C, dissolve them with 60 g chloroform/methanol (mass ratio 4:1), and mix well. The above solution was placed in a rotary evaporator, and chloroform and methanol were distilled off under reduced pressure to obtain a lipid film. A phosphate buffer solution with a pH of 6 was added to a lipid film flask, rotated in a 50° C. temperature bath on a rotary evaporator for 2 h, ultrasonicated in a water bath for 20 min, and passed through a 0.22 μm filter membrane to prepare flurbiprofen liposomes.

Example 6

Weigh 150.0 mg flurbiprofen, 120.0 mg egg yolk lecithin, 30.0 mg cholesterol, and 30.0 mg vitamin C, dissolve them with 60 g chloroform/methanol (mass ratio 4:1), and mix well. The above solution was placed in a rotary evaporator, and chloroform and methanol were distilled off under reduced pressure to obtain a lipid film. Phosphate buffer solution with a pH of 8 was added to a lipid film flask, rotated in a 50° C. temperature bath on a rotary evaporator for 2 h, ultrasonicated in a water bath for 20 min, and passed through a 0.45 μm filter membrane to prepare flurbiprofen liposomes.

Claims (2)

1. flurbiprofen liposome is characterized in that: be made up of following parts by weight:

1～10 part in cholesterol

2～50 parts of flurbiprofens

5～40 parts of Ovum Gallus domesticus Flavus lecithins

1～10 part of vitamin C.

2. the preparation method of the described a kind of flurbiprofen liposome of claim 1, it is characterized in that: take by weighing earlier 1～10 part in cholesterol by weight, 5～40 parts of Ovum Gallus domesticus Flavus lecithins, 1～10 part of 2～50 parts of flurbiprofens and vitamin C, the reuse chloroform/methanol makes their dissolvings, and mix homogeneously obtains mixed solution, then above-mentioned mixed solution is placed Rotary Evaporators, chloroform and methanol are removed in distilling under reduced pressure, make lipid film, then be that 6～8 phosphate buffer joins in the lipid film with pH, in bathing, 20～60 ℃ of temperature rotating 1～4h on the Rotary Evaporators, behind the last ultrasonic 5～30min of water-bath, the filter membrane of crossing 0.22～0.45 μ m makes flurbiprofen liposome;

Above-mentioned chloroform/methanol is a chloroform: methanol=4: 1 mass ratioes;

The consumption of above-mentioned chloroform/methanol is 2000～20000 times of cholesterol consumption.