TW201605491A - Carrier enhancing absorption of medication - Google Patents

Abstract

A carrier enhancing absorption of medication includes a target medication, an emulsifier, a small-molecular hyaluronic acid (HA) component, an absorption enhancer and a cream base, wherein the carrier promotes infiltration of target medication from skin over affected area and enhances the absorption efficacy of human body by synergistic interaction.

Description

Carrier with enhanced drug absorption effect

The present invention relates to a carrier for enhancing the absorption of a drug, and more particularly to a synergistic action of the composition to achieve augmentation such as glucosamine, a nonsteroidal anti-inflammatory drug, an analgesic, a hormone preparation. And other drug absorption effects.

Based on the drug delivery system (DDS), the active ingredients in the ointment can be absorbed through the skin. Therefore, many pharmaceutical products are manufactured into creamy or ointment-like products, and the skin on the outside of the affected part or affected part is utilized by the characteristics of skin absorption. After smearing, the active ingredients of the drug can be directly absorbed and utilized. Compared with oral administration or injection, the accuracy and effective ratio of the drug product to the target affected part can be greatly improved. Patients with cancer at the end of the cancer are basically unable to take the drug orally or by injection. It is more appropriate to apply the skin for absorption. Further, oral glucosamine has an effect of promoting chondrocyte proliferation, and thus is widely used for treating or relieving joint deterioration. However, if administered orally, glucosamine requires a large dose and is not easily accessible to the target organ, and thus has a need for oral preparation.

Because the cream is the water phase and the oil phase are evenly dispersed by the emulsifier, the traditional cream has a sticky and heavy feeling, so that the user does not like to use it subjectively, and the small molecule polyethylene glycol PEG has carcinogenicity. doubt. And the skin is a protective organ, except for small molecules and sterols, others are not easily absorbed.

In order to improve the above shortcomings, the present invention has made the following improved formulation for enhancing the drug absorption effect. For the added aqueous or oily components, since the particle size becomes smaller after emulsification, the absorption rate increases, and then the absorption enhancer enhancer, carrier. .., etc., can improve the rate of transdermal absorption, in order to achieve the purpose of enhancing the absorption of drugs.

The present invention relates to a carrier having an intensive drug absorption effect, which mainly comprises: a target drug; an emulsifier; a small molecule hyaluronic acid component; an absorption enhancer component; and a cream base; the composition by the component thereof Synergistically interact to promote the penetration of the target drug component into the skin of the affected part, in order to enhance the body's absorption effect.

The main object of the present invention is: according to the principle of DDS, the smaller the emulsified particles, the more the amount of absorption through the skin. In order to improve the absorption of the target drug in the cream, the emulsifier and the cream base used in the present invention have small emulsified particles. It is easily absorbed by human skin, and the use of small molecule hyaluronic acid as a carrier of the target drug is more absorbed by human skin.

Another object of the present invention is that the composition of the present invention can be directly applied to the skin of the affected part, and after being absorbed by the skin of the affected part, in addition to the target drug, emulsifier, small molecule hyaluronic acid (HA), absorption enhancer, The cream base can increase the absorption effect, and the seaweed extract (Oligogeline) can be further added to form a patch protection on the outer layer of the application, and the blood circulation promoter promotes the percutaneous absorption effect of the target drug and helps the blood. Circulate, promote metabolism, and increase absorption of active ingredients.

A further object of the present invention is that most of the general cosmetic or cream compositions use polyethylene glycol PEG derivatives as humectants and thickeners, but in recent years, small molecule polyethylene glycol PEG has been confirmed by the US FDA as Carcinogens, therefore, the formulation of the present invention further uses polyethylene glycol (PEG FREE)-free ingredients to reduce the health and safety concerns of the user.

The invention relates to a carrier with enhanced drug absorption effect, which mainly comprises:

a) a target drug; the target drug may be Glucosamine HCL, a non-steroidal anti-inflammatory drug, an analgesic, a hormone preparation or the like.

b) an emulsifier; most of the emulsifiers in general cosmetic or cream compositions use polyethylene glycol PEG derivatives should be used as a moisturizer and thickener, but in recent years, small molecule polyethylene glycol PEG has been confirmed by the US FDA As a carcinogen, the formulation of the present invention further uses a component that does not contain polyethylene glycol (PEG FREE). For example, the present invention is a biomimetic layered liquid crystal emulsifier of natural origin, which has small particles and is easy to use. It is absorbed by human skin. Moreover, it does not contain polyethylene glycol PEG and ethylene oxide EO (Ethylene oxide), and has little impact on human body and environmental impact. For example, an emulsifier of Emulgade® PL68/50 can be used in the present invention.

According to the DDS principle, the smaller the emulsified particles, the more the amount absorbed by the skin. The emulsifier used in the present invention is a biomimetic layered liquid crystal emulsifier of natural origin, and the emulsification effect is good, and the granules produced by the emulsification are much smaller than the general one. Emulsifiers are more easily absorbed by the body.

c) a small molecule of hyaluronic acid (HA): small molecule hyaluronic acid (HA) with an average molecular weight of 5000-6000, its molecular size is about 25 nm, as a drug carrier, can directly cross the keratinocyte space, Through the sweat glands, cell gaps, pores are absorbed, small molecule hyaluronic acid not only has the characteristics of general traditional macromolecular hyaluronic acid, but also anti-allergic and anti-oxidation effects, and its weight percentage is 0.1%~1%.

d) an absorption enhancer component: the absorption enhancer component may be isosorbide dimethyl ether Dimethyl Isosorbide (DMI) is an organic solvent which is not less than medicinal, which can uniformly disperse the active ingredient and increase the absorption rate. Its weight percentage is 1% to 36%.

e) A cream base.

f) A seaweed extract (Oligogeline) component: it is a seaweed extract from the ocean, which has the property of repairing the skin, also known as the sea band, which allows the cream base and other ingredients to be evenly dispersed in the product. And when applied to the target site, a patch is formed on the surface of the composition in contact with the air to secure the composition to the target skin. It can effectively reduce the moisture escape of the composition, protect the internal composition from falling off due to user action or frictional wear, and increase the absorption of the active ingredient of the target drug, wherein the weight percentage of the seaweed extract (Oligogeline) is 1% to 10%. .

g) a blood circulation promoter component: the blood circulation promoter component may be menthol, capsicum Frutescens. Methanol and Capsicum Frutescens help blood circulation, promote metabolism, increase the absorption of active ingredients, and provide a refreshing taste and a refreshing feeling, which can improve the feeling of relieving discomfort in the affected area. Mentium and Capsicum Frutescens are 0.1% to 1% by weight.

Based on the above formula design, the present invention can be directly applied to the skin of the target site, and the active ingredient of the target drug is absorbed through the skin. After allowing these ingredients to be absorbed through the skin, they can directly act on the target site to improve the target symptoms and enhance the absorption of the drug.

In order to verify that the present invention does have the aforementioned various effects, the applicant further carried out the following experimental design of the absorption effect, wherein the target drug is, and is subjected to an experimental test by a third-party medical unit with credibility.

(1) Executing unit: Innovation and Cultivation Center of Ma Rong Memorial Hospital.

(2) Executor: Zhuang Zhiguang, Technical Director, Medical Research Department, Ma Rong Memorial Hospital.

(III) Experimental design, cortical treatment of nude mice: The cortex used in this study was the cortex of the back of nude mice. After the cortex was cut from the animal body, the muscle layer on the cortex was removed with a scalpel and then diluted with saline. The sex cleaner removes grease and dirt from the skin layer, and finally is washed 3 to 5 times with physiological saline and cut into a size of about 2 cm x 2 cm.

(4) Transdermal absorption test: All samples were subjected to six repeated tests, and the formulation was tested at room temperature by a vertical external transdermal absorbance apparatus (Franz cell) to determine whether the formulation delivered glucosamine through the cortex. The vertical Franz cell is a two-part glass structure, the upper part is a drug-loading trough, and the lower part is a receiving trough. Before the test skin layer is sandwiched, the receiving trough needs to be filled with physiological saline and a micro-rotor. Then, after the cortex is laid flat, the rack is loaded with the medicine tank and fixed by metal clips. Finally, 2 ml of the test recipe is added to the drug-loading tank and sealed with parafilm, and the Franz cell is placed on the electromagnetic stirrer to continuously rotate the micro-rotor, and At the set time point (0, 2, 4, 6, 24 hr), 50 ul of the sample in the receiving tank was taken out from the sampling tube.

(5) Experimental group and control group: Table 1 is the formula composition table of the example in the present case, wherein group D is the control group. Table 1, Example Formulation Table

(6) Sample analysis: 50 ul of the sample taken from the receiving tank of the percutaneous absorption apparatus was centrifuged at 12,000 rpm for 30 minutes, and then the supernatant was placed in an analysis tube dedicated to a liquid chromatography tandem mass spectrometer. The operating conditions of the liquid chromatography tandem mass spectrometer were as follows: the separation column was Luna silica 100A (2x50 mm, 5 um), the mobile phase A was 0.01% formic acid, and the mobile phase B was 1 mM NH ₄ OAc + 0.1% formic acid in 100% acetonitrile, the gradient elution conditions are shown in Table 3. The main signal appears when the extraction time is about 2.3 minutes. The area under the signal is compared with the standard curve by the integral to obtain the value D (ng/ml), and the groove volume V (ml) is accepted by the formula D (ng/ml) × ÷ The permeability of the sample P (cm ² ) is converted into the permeability P (ng/cm ² ) of the sample. Table 3: Operating conditions of liquid chromatography tandem mass spectrometer

(VII) Results: According to the analysis data, the D sample does not contain glucosamine (Table 4). From the trend of six-hour penetration (Fig. 1), E penetrates the cortex preferably to 180 ug/cm ² , and F is not far from about 50 to 60 ug/cm ² . The data was infiltrated at 24 hours (Fig. 1), and E and F reached 300 ug/cm ² or more. Table 4: Transdermal absorption data for the EF formulation, where D does not contain glucosamine and is therefore not shown in the table. AVE: average value (ng/cm ² ), SE: standard errors.

From the above results, it is understood that the cream composition of the present invention can effectively promote the glucosamine absorption effect after 2 hours, 4 hours, 6 hours or even 24 hours, and has the effect of achieving the object of the present invention.

The above embodiments are merely illustrative of the invention and are not intended to limit the scope of the invention. Any modifications or variations that are made without departing from the spirit of the invention are intended to be protected.

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Figure 1 is a graph showing the penetration data of the dermal absorption experiment of the present invention.

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Claims (9)

A carrier for enhancing drug absorption effect, which mainly comprises: at least one target drug; an emulsifier; a small molecule hyaluronic acid (HA) component; an absorption enhancer component; and a cream base; the composition by the component thereof Synergistically interact to promote the penetration of the target drug component into the skin of the affected part, in order to enhance the body's absorption effect. The intensive drug absorption effect carrier according to claim 1, wherein the target drug is at least one of a drug such as Glucosamine HCL, a non-steroidal anti-inflammatory drug, an analgesic agent, and a hormone preparation. The carrier for enhancing drug absorption effect according to claim 1, wherein the emulsifier is a biomimetic layered liquid crystal emulsifier of natural origin. The carrier for enhancing drug absorption effect according to claim 1, wherein the small molecule hyaluronic acid (HA) has a molecular weight of 5000-6000 and a weight percentage of 0.1% to 1%. The intensive drug absorption effect carrier according to claim 1, wherein the cream base further comprises an Oligogeline component in a weight percentage of 1% to 10%. The carrier for enhancing drug absorption effect according to claim 1, wherein the weight percentage of the absorption enhancer component is from 1% to 36%. The intensive drug absorption effect carrier according to claim 6, wherein the absorption enhancer component is isopropylidene dimethyl ether Dimethyl Isosorbide (DMI). The intensive drug absorption effect carrier according to claim 1, wherein the cream base further comprises a blood circulation promoter component in a weight percentage of 0.1% to 1%. The intensive drug absorption effect carrier according to claim 8, wherein the blood circulation promoter component is menthol Methanol and Capsicum Frutescens.