Soft gelatin capsule containing angelica oil

Details Soft gelatin capsule containing angelica oil Soft gelatin capsule containing angelica oil

2001-03-01

2004-06-22

Spear, James M. (Department: 1615)

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Capsules

C424S451000, C424S456000, C514S783000

Reexamination Certificate

active

06753010

ABSTRACT:

The present invention relates to a novel dosage form of angelica essential oil (soft gelation capsule containing angelica essential oil) and preparation thereof.
The available dosage form of angelica essential oil at present is under the Chinese name of Fu Tong Ning, a kind of dropping pill which has been taken on <<Drug Standard WS
3
-B-3191-98>> of the Ministry of Public Health, PRC. Among them the standard of angelica essential oil, as an active constituent has been taken on the <<Local Standard of Gansu Province (GWYZZ (85) No. 584>> and the medicinal material,
Angelica sinensis
has been taken on the <<Pharmacopeia of the People's Republic of China>> 1995 Edition, Part 1. The process for preparing said dropping pill is as follows: Angelica essential oil is poured into a mixed liquor of polyethylene glycol 6000 (melted at 100-110° C.) and stearic acid, then it is mixed homogenously and prepared with the method of dropping and enteric coating. The product is thus made. Angelica essential oil used for preparing Fu Tong Ning dropping pill is extracted from the crude drug (Chinese angelica root) by means of steam distillation. The modern pharmaceutical research has proved that angelica essential oil possesses the action of dual-directional regulation on uterine smooth muscle. A further study has discovered that the principal active ingredient in angelica essential oil is ligustilide which possesses a stronger anticholinergic action. However, ligustilide can isomerize easily and the therapeutic effects of the drug are influenced by deactivation due to the partial isomerization of ligustilide under the circumstance of high temperature. Even so, in the case of the original dropping pill the preparation of angelica essential oil is carried out under a circumstance of high temperature (100-110° C.). Certainly, it causes isomerization of ligustilide as an active component and the therapeutic effect of drug is finally influenced.
The present invention is just aimed at the existing drawback of dropping pill of angelica essential oil in the prior art, in order to research and develop a soft gelation capsule of new dosage form for angelica essential oil.
The object of the present invention is just to provide a soft gelation capsule of new dosage form for angelica essential oil.
The soft gelation capsule of angelica essential oil in the present invention consists of capsule material and oil with medicinal liquor, in which the oil with medicinal liquor consists of angelica essential oil and vegetable oil as diluents. The weight ratio of two kinds of oil is in 1:0-30 (preferably 1:2-20; more preferably 1:7-10; most preferably 1:9). Among them angelica essential oil can be obtained by employing steam distillation followed by extraction, and also by CO
2
-supercritical fluid extraction. In the present invention angelica essential oil is preferably obtained by the mean of CO
2
-supercritical extraction. When this method is adopted for extracting angelica essential oil, the working condition is as follows: pressure, 15-35 Mpa; temperature, 30-55° C.; time for extraction, 2-20 hours ; CO
2
flow, 1-10 L/kg of
Angelica sinensis
·hour. Optimized conditions for extraction are as follows: pressure, 20-30 Mpa ; temperature, 35-50° C.; time for extraction, 5-8 hours ; CO
2
flow, 2-6 L/kg of
Angelica sinensis
·hour. The vegetable oil may be one oil selected from the group consisting of sesame oil, peanut oil, corn oil, bean oil, almond oil, peach-kernel oil, cotton seed oil, sunflower seed oil, castor oil and olive oil, preferably sesame oil, peanut oil, corn oil, bean oil and olive oil, while corn oil is the best. The capsule materials consist of gum type of material, plasticizer, water and additive. Among them the gum type of material may be gelatin, or Arabic gum or mixture thereof, wherein the preferred is gelatin. Among them the gelating strength of gelatin is generally in the range of 150-250 brumk and the range of viscosity is 25-45 mPa·S. The plasticizer may be glycerin, sorbitol or mixture thereof. Among them glycerin is preferred. Additive agents may be an antiseptic, such as a mixture of methyl p-hydroxybenzoate (1.6%) and propyl p-hydroxybenzoate (0.04%). When the gelatin is selected as gel material, the weight ratio of dried substance of gelatin and plasticizer is in 1:0.4-0.6 and that of water and dried gelatin is in 1: 0.7-1.4. An additional agent may be light-screening agent which can be Fe
2
O
3
, TiO
2
, pigment, preferably Fe
2
O
3
. Among them the amount of Fe
2
O
3
is 0.0075-0.75 mg/kg gelatin.
The soft gelation capsule of the present invention can be made by adopting a conventional preparative process for soft gelation capsule, for example, molding method by hand, rotary molding method or dropping method. Generally, the pressing method, such as rotary molding method is selected preferably. If an autorotatory capsule pressing is employed, the temperature is controlled at 40-50° C., in order to make each capsule containing 10 mg of angelica essential oil.
Soft gelation capsule as the new dosage form of angelica essential oil in the present invention has overcome the drawback in the original dosage form of angelica essential oil as dropping pill because a principal constituent in angelica essential oil is ligustilide which can easily isomerized under an environment of high temperature (such as 100° C.) and thus the content of angelica essential oil is decreased. However, the content of ligustilide in angelica essential oil is relatively stable under the room temperature of 20° C. (see also Example 1 in detail ). The fact that angelica essential oil in dropping pill is added with stirring and dissolving into a mixture of completely melted (100-110° C.) polyethylene glycol 6000 and stearic acid obviously cause an considerable decreasement of content of ligustilide in angelica essential oil. As a result, soft gelation capsule is prepared under temperature of 40-50° C. by press method and the amount of ligustilide in angelica essential oil is this be greatly preserved.
Furthermore, the present invention not only avoid the loss of ligustilide in angelica essential oil by changing dosage form of angelica essential oil, but also obtain angelica essential oil containing higher content of ligustilide by means of improving extraction of angelica essential oil, such as CO
2
-supercritical extraction under a condition of low temperature. In prior art angelica essential oil is extracted with the traditional process of steam distillation. This method causes some trouble to lower the content of ligustilide in angelica essential oil due to unstability of ligustilide to heat. Making a comparison between steam distillation and CO
2
-supercritical extraction by means of GC-MS analysis, it has been found that the chemical composition of volatile components of angelica essential oil obtained from the above-mentioned two extraction methods are basically the same, but by means of CO
2
-supercritical extraction the content of (Z)-ligustilide is increased from 53.99% to 74.54% and (E)-ligustilide 3.18% to 9.11% respectively (see also Example 2).
In short, the present new dosage form (soft gelation capsule containing angelica essential oil) has overcome the drawback from the original one (dropping pill) in many aspects, especially with loss of ligustilide, an active component of angelica essential oil.
Experimental Example 1
Influence of Temperature on Ligustilide Content in Angelica Essential Oil
1.1 Apparatus and Reagents
Gas chromatograph (Shimadzu GC-14B); Diethyl phthalate (Shanghai First Reagents Factory, purity is 99.7% tested by gas chromatography with area normalization method); angelica essential oil (991007).
1.2 Experimental Methods
Test group: Five portions of angelica essential oil (30 &mgr;l each) are placed separately in five 7 ml-sealing vials numbered with 0, 1, 2, 3 and 4, weighed accurately and sealed. The vials are laid in an oven (100° C.) and the samples are taken out of the oven after 0, 1, 2, 3 and 4 hours respectively. Anabout 16 &mgr;l

Affiliated with

Also associated with

Rating

Soft gelatin capsule containing angelica oil does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Soft gelatin capsule containing angelica oil, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Soft gelatin capsule containing angelica oil will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3304706