CN116059239A

CN116059239A - Composition containing cannabidiol and application thereof

Info

Publication number: CN116059239A
Application number: CN202111269946.4A
Authority: CN
Inventors: 陈琦; 王冉; 连萌; 常坦然; 李如彦; 李庆中
Original assignee: Yunnan Hanmeng Pharmaceutical Co ltd
Current assignee: Yunnan Hanmeng Pharmaceutical Co ltd
Priority date: 2021-10-29
Filing date: 2021-10-29
Publication date: 2023-05-05

Abstract

The invention provides a composition containing cannabidiol and application thereof, wherein the composition comprises cannabidiol, cannabis polysaccharide, retinol, hydroxyasiaticoside, ergothioneine and glabridin. The composition provided by the invention has the effects of resisting inflammation, inhibiting tyrosinase activity, resisting oxidation and the like, has a synergistic effect in the aspects of resisting inflammation, inhibiting tyrosinase activity and the like, and has an obvious effect of improving inflammatory pigmentation.

Description

Composition containing cannabidiol and application thereof

Technical Field

The invention belongs to the field of medicine research and development, and particularly relates to a cannabidiol-containing composition and application thereof, in particular to a cannabidiol-containing composition with a good effect of improving inflammatory pigmentation and application thereof.

Background

Allergic dermatitis, and skin inflammations such as irritant skin inflammation, eczema, neurodermatitis and the like caused by external environmental factors are common and frequently encountered diseases of dermatology, seriously affect the quality of life of human beings, mainly use hormone medicines for treating the diseases at present, only temporarily treat the diseases, and easily cause hormone-dependent dermatitis. In addition, inflammation is also prone to skin pigmentation, post-inflammatory Pigmentation (PIH) is a rare skin pigmentation disease state associated with increased melanin synthesis and deposition, destruction of basal cell layers after inflammation leads to increased pigment incontinence, superficial dermis melanocyte phagocytes increase, macrophages engulf basal layer keratinocytes and melanocytes, these melanin persist in the superficial dermis for a period of time, and epidermal inflammatory reactions lead to release of arachidonic acid and oxidation to form prostaglandins and leukotrienes, these inflammatory mediators change the activity of melanocytes and some immune cells by stimulating the melanocytes of the surface layer, ultimately leading to increased melanin synthesis, pigment transfer to surrounding keratinocytes, leading to increased epidermal pigment.

Currently, common drugs used to treat post-inflammatory pigmentation are azelaic acid, kojic acid, licorice extract tyrosinase inhibitors or chemical skin rejuvenating compounds such as salicylic acid, glycolates. The product has no obvious effect on inflammatory color spots, so that aiming at pigment deposition caused by inflammation, the product for solving the problem of the inflammatory pigment deposition is developed by combining other pigment deposition causes and comprehensively considering the reasons, and has important significance in mechanism. A plurality of whitening products in the market at present mainly combine with a certain component to inhibit tyrosinase so as to achieve the effect of whitening and fading spots. Most are symptomatic medications for these simple common causes, and many compositions ignore inflammation and are one of the main causes of pigmentation. Therefore, how to provide a drug with good anti-inflammatory effect becomes a problem to be solved urgently.

Disclosure of Invention

In view of the shortcomings of the prior art, the invention aims to provide a cannabidiol-containing composition and application thereof, and particularly provides a cannabidiol-containing composition with a good effect of improving inflammatory pigmentation and application thereof. The composition provided by the invention has the effects of resisting inflammation, inhibiting tyrosinase activity, resisting oxidation and the like, has a synergistic effect in the aspects of resisting inflammation, inhibiting tyrosinase activity and the like, and has an obvious effect of improving inflammatory pigmentation.

In order to achieve the aim of the invention, the invention adopts the following technical scheme:

in a first aspect, the present invention provides a cannabidiol-containing composition comprising cannabidiol, cannabis polysaccharide, retinol, droxypenside, ergothioneine, and glabridin.

According to the invention, by selecting cannabidiol, cannabis polysaccharide, retinol, hydroxydroxypenside, ergothioneine and glabridin to be compounded, the composition has a synergistic effect in the aspects of anti-inflammatory, tyrosinase activity inhibition and the like, the anti-inflammatory effect of the composition is obviously improved, melanin can be effectively desalted, and especially the inflammatory pigmentation is well improved.

Preferably, the composition comprises, in parts by weight, 0.8-1.2 parts of cannabidiol, 0.1-3 parts of cannabis polysaccharide, 0.1-5 parts of retinol, 0.2-2 parts of hydroxyasiaticoside, 0.5-2 parts of ergothioneine and 0.1-3 parts of glabridin.

Wherein, the parts of cannabidiol may be 0.8 parts, 0.9 parts, 1 part, 1.1 parts or 1.2 parts, etc., the parts of cannabis polysaccharide may be 0.1 parts, 0.2 parts, 0.3 parts, 0.5 parts, 1 parts, 1.5 parts, 2 parts, 2.5 parts or 3 parts, etc., the parts of retinol may be 0.1 parts, 0.2 parts, 0.3 parts, 0.5 parts, 1 parts, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts or 5 parts, etc., the parts of madecassoside may be 0.2 parts, 0.3 parts, 0.4 parts, 0.5 parts, 0.6 parts, 0.7 parts, 0.8 parts, 0.9 parts, 1 parts, 1.1 parts, 1.2 parts, 1.3 parts, 1.4 parts, 1.5 parts, 1.6 parts, 1.7 parts, 1.8 parts, 1.9 parts, etc., the parts of ergothioneine may be 0.5 parts, 0.6 parts, 0.7 parts, 0.8 parts, 0.9 parts, 1 parts, 1.1 parts, 1.2 parts, 1.3 parts, 1.4 parts, 1.5 parts, 1.6 parts, 1.7 parts, 1.8 parts, 1.9 parts, or 2 parts, etc., and the parts of glabridin may be 0.1 parts, 0.2 parts, 0.3 parts, 0.5 parts, 1 parts, 1.5 parts, 2 parts, 2.5 parts, or 3 parts, etc., but are not limited to the values recited above, and other non-recited values within the above ranges are equally applicable.

Preferably, the composition comprises, in parts by weight, 0.8-1.2 parts of cannabidiol, 0.5-2 parts of cannabis polysaccharide, 0.1-2 parts of retinol, 0.5-1 part of hydroxyasiaticoside, 0.5-1.8 parts of ergothioneine and 0.1-2 parts of glabridin.

The proportion of the specific components can further improve the effects of resisting inflammation and inhibiting tyrosinase activity of the composition, play a better role in resisting inflammation, repairing and fading melanin, and fundamentally improve the problem of inflammatory skin.

The cannabis polysaccharide is a heteropolysaccharide extracted from industrial cannabis, for example, from industrial cannabis leaves, and forms a three-dimensional network structure through intramolecular and intermolecular hydrogen bonds, so that a great deal of interactions can be generated between lipid and sugar chains among cells of the stratum corneum, and the interactions are adsorbed on the surface of skin to form an elastic and adhesive continuous biological film, thereby playing a role in repairing skin barriers.

The cannabis polysaccharide is prepared by a preparation method comprising the following steps:

(1) Mixing industrial hemp leaf raw material with water, adding acid to adjust pH to 3.0-3.5, reflux extracting for 1-3 times, reflux each time for 1-3h, mixing extractive solutions to obtain primary extract of hemp polysaccharide;

(2) Purifying the primary cannabis polysaccharide extract obtained in the step (1) by anion exchange resin D900 column chromatography, eluting with water, collecting effluent, and spray-drying to obtain cannabis polysaccharide;

the volume of the water in the step (1) is 5-10L based on the mass of the industrial hemp leaf raw material of 1 Kg; the acid is one or a combination of at least two of formic acid, acetic acid, oxalic acid, citric acid, hydrochloric acid, nitric acid or sulfuric acid; the mass of the resin in the step (2) is 1/30-1/100 of the mass of the industrial hemp flower leaf raw material.

In a second aspect, the present invention provides the use of a composition as described above in the manufacture of an anti-inflammatory medicament.

In a third aspect, the present invention provides the use of a composition as described above in the preparation of an inhibitor of tyrosinase activity.

In a fourth aspect, the invention provides the use of a composition as described above in the manufacture of a medicament for lightening melanin.

Preferably, the melanin is caused by inflammatory pigmentation.

In a fifth aspect, the present invention also provides a medicament for lightening inflammatory pigmentation-type stains, the medicament comprising a composition as described above.

Preferably, the dosage form of the medicament comprises any one of cream, patch, spray, ointment, plaster, emulsion, smear or mud.

The medicament also comprises pharmaceutically acceptable auxiliary materials, wherein the auxiliary materials comprise any one or a combination of at least two of diluents, solubilizers, emulsifiers, moisturizers, thickeners, carriers or fillers, such as a combination of diluents and solubilizers, a combination of solubilizers and emulsifiers or a combination of moisturizers and thickeners, and the like, but are not limited to the above-listed combinations, and other non-listed combinations in the above-listed combination range are also applicable.

Preferably, the carrier comprises any one of a liposome, micelle, dendrimer, microsphere or microcapsule.

The composition can be loaded on the medicinal carrier to be used as a medicament for lightening melanin, so that better biocompatibility, targeting property, biosafety and administration effect are realized.

Compared with the prior art, the invention has the following beneficial effects:

the invention provides a composition containing cannabidiol, which has synergistic effects in the aspects of anti-inflammatory, tyrosinase activity inhibition and the like by selecting cannabidiol, cannabis polysaccharide, retinol, hydroxyasiaticoside, ergothioneine and glabridin for compounding, and can obviously improve the anti-inflammatory effect of the composition, effectively lighten melanin and particularly has good effect of improving inflammatory pigmentation.

Detailed Description

In order to further describe the technical means adopted by the present invention and the effects thereof, the following describes the technical scheme of the present invention in combination with the preferred embodiments of the present invention, but the present invention is not limited to the scope of the embodiments.

Preparation example 1 preparation of cannabis polysaccharide

The preparation example provides cannabis polysaccharide, which comprises the following specific steps:

(1) Mixing 10kg of industrial hemp leaf raw material with 50L of water, adding acetic acid to adjust pH to 3.0, reflux-extracting for 3 times, reflux-extracting for 1h each time, and mixing the extracting solutions to obtain primary cannabis polysaccharide extract;

(2) Subjecting the primary cannabis polysaccharide extract obtained in the step (1) to anion exchange resin D900 column chromatography (resin dosage is 350 g), eluting with water until effluent is colorless, collecting effluent, and spray drying to obtain cannabis polysaccharide 758.09g.

Example 1

The embodiment provides a composition, which comprises the following raw materials in parts by weight:

1 part of cannabidiol, 1.2 parts of cannabis polysaccharide obtained in preparation example 1, 1 part of retinol, 0.7 part of madecassoside, 1.2 parts of ergothioneine and 1 part of glabridin.

The preparation method comprises the following steps: pulverizing cannabidiol, cannabis polysaccharide, retinol, hydroxydroxypenside, ergothioneine and glabridin, and mixing to obtain the composition.

Example 2

0.8 part of cannabidiol, 2 parts of cannabis polysaccharide obtained in preparation example 1, 0.1 part of retinol, 1 part of madecassoside, 0.5 part of ergothioneine and 2 parts of glabridin.

Example 3

1.2 parts of cannabidiol, 0.5 part of cannabis polysaccharide obtained in preparation example 1, 2 parts of retinol, 0.5 part of madecassoside, 1.8 parts of ergothioneine and 0.1 part of glabridin.

Example 4

0.8 part of cannabidiol, 3 parts of cannabis polysaccharide obtained in preparation example 1, 0.1 part of retinol, 2 parts of madecassoside, 0.5 part of ergothioneine and 3 parts of glabridin.

Example 5

1.2 parts of cannabidiol, 0.1 part of cannabis polysaccharide obtained in preparation example 1, 5 parts of retinol, 0.2 part of madecassoside, 2 parts of ergothioneine and 0.1 part of glabridin.

Comparative example 1

This comparative example provides a composition in accordance with example 1 except that the composition does not contain cannabidiol and the reduced portion is proportionally distributed to the other materials.

The preparation method is described in example 1.

Comparative example 2

This comparative example provides a composition which is identical to example 1 except that the cannabis polysaccharide obtained in preparation example 1 is not included in the composition and the reduced portion is proportionally distributed to the other materials.

The preparation method is described in example 1.

Comparative example 3

This comparative example provides a composition consistent with example 1 except that the composition does not contain retinol and the reduced portion is proportionally distributed to the other materials.

The preparation method is described in example 1.

Comparative example 4

This comparative example provides a composition in accordance with example 1 except that the composition does not contain madecassoside and the reduced fraction is proportionally distributed to the other ingredients.

The preparation method is described in example 1.

Comparative example 5

This comparative example provides a composition consistent with example 1 except that the composition does not contain ergothioneine and the reduced fraction is proportionally distributed to other materials.

The preparation method is described in example 1.

Comparative example 6

This comparative example provides a composition in accordance with example 1 except that the composition does not contain glabridin and the reduced portion is proportionally distributed to the other materials.

The preparation method is described in example 1.

Skin irritation test:

according to the test method of acute skin irritation of "cosmetic safety technical Specification", the compositions provided in examples 1-5 and comparative examples 1-6 were respectively mixed with PEG-40 hydrogenated castor oil and water (sample 6g, PEG-40 hydrogenated castor oil 6g, and after stirring slightly heated 45 ℃ until dissolved uniformly, water was added and mixed until 100g was sufficient), and then divided into 11 groups, each group was correspondingly selected from 4 white rabbits, and it was required that the compositions should be adult, healthy, and skin-friendly. The hairs on the two sides of the back spine of the experimental animal are cut off 24 hours before the experiment, the epidermis can not be damaged, and the left and right hair removing ranges are respectively 3cm multiplied by 3cm. 1mL of the test composition was applied directly to the skin, and then covered with two layers of gauze (2.5 cm. Times.2.5 cm) and one layer of cellophane, and fixed with a non-irritating adhesive tape and bandage. The other side skin served as a control. The application time was 2h using the blocking test. After the test is finished, the residual substances are cleaned by warm water, the skin is not abraded by light rubbing, and the minimum test error is ensured. And (5) observing whether the skin reaction at the smearing part has erythema, congestion, pallor swelling and erosion after removing the test object for 1, 24, 48 and 72 hours. The results were recorded as follows:

wherein "0" indicates no physical sign, no abnormal phenomena such as erythema, congestion, pale swelling, erosion and the like; "1" means a slight sign, with a slight reddening after use; "2" means light sign: redness and swelling after use; "3" means a heavy sign: congestion, swelling, erosion and the like occur after the use.

The results show that the product provided by the invention has no stimulation to human skin and good safety.

Anti-inflammatory efficacy test:

female mice (CD-1) were sampled 95 and grouped, each group of 5 mice was divided into a control group, a model group and an experimental group, and the experimental part was molded by applying 1. Mu.L of acetone solution (TPA) using 1.5mol of phorbol ester. The specific operation is as follows:

control group: smearing the ears of the mice with 1 μl of acetone, and smearing once again after 10 min;

model group: coating the ears of the mice with 1 mu L of TPA, and coating the ears with TPA once again after 10 min;

experimental group: the ears of mice were smeared with 1 μl of TPA, followed by 1 μl of each test solution, respectively, and half an hour later, with TPA.

The preparation method of the test solution is consistent with the test in the skin irritation test, wherein the test subjects are the compositions provided in examples 1-5 and comparative examples 1-6, and the raw materials cannabidiol, cannabis polysaccharide, retinol, hydroxyasiaticoside, ergothioneine and glabridin.

The above steps were cycled for 6 days, and after 5 hours of application on the last day, the ears of each mouse were perforated, the diameter was 5mm, the obtained ear tissue samples were weighed and recorded, and the weight of the ears represented the swelling degree of inflammation, and the calculation formula was as follows:

inhibition of inflammation (%) = (swelling degree of model group-swelling degree of administration group)/model swelling degree×100%;

the swelling degree of the model group and the swelling degree of the administration group were changes in weight relative to the control group.

The results were as follows:

group of	Inhibition ratio (%)	Group of	Inhibition ratio (%)	Group of	Inhibition ratio (%)
						Example 1	46	Comparative example 2	29	Hemp polysaccharide	8
Example 2	44	Comparative example 3	29	Retinol	7
						Example 3	42	Comparative example 4	25	Madecassoside	11
Example 4	39	Comparative example 5	30	Ergothioneine	7
						Example 5	37	Comparative example 6	32	Glabridin	7
Comparative example 1	28	Cannabidiol	9

The data show that the product provided by the invention has excellent anti-inflammatory effect, and the inhibition rate of the product to inflammation reaches more than 37%; comparing example 1, comparative examples 1-6 and the respective raw material groups, it can be found that the anti-inflammatory effect of the composition is significantly improved by compounding six raw materials and synergistically acting.

Inhibition effect experiment on tyrosinase activity:

1. solution to be prepared

(1) Preparing a buffer solution (PBS) with a pH value of 6.8;

(2) Preparing tyrosinase solution with the mass concentration of 0.08 mg/mL;

(3) Preparing an L-tyrosine solution with the mass concentration of 1.0 mg/mL;

(4) Liquid to be measured A:2.0mL PBS buffer+0.5 mL tyrosinase solution+0.5 mL L-tyrosine solution;

(5) Liquid B to be measured: 2.5mL PBS buffer+0.5 mL tyrosinase solution;

(6) Liquid C to be measured: 0.5mL of sample solution+1.5 mL of PBS buffer+0.5 mL of tyrosinase solution+0.5 mL of L-tyrosine solution (note that the preparation method of the sample solution is consistent with the test in the skin irritation test, and the samples to be tested are the compositions provided in examples 1-5 and comparative examples 1-6, and the raw materials cannabidiol, cannabis polysaccharide, retinol, hydroxyasiaticoside, ergothioneine and glabridin);

(7) Liquid D to be measured: 0.5mL of sample solution+2.0 mL of PBS buffer+0.5 mL of tyrosinase solution.

2. Calculation formula of tyrosinase inhibition rate in experimental process

The prepared various solutions are firstly placed in a water bath kettle at 37 ℃ for 30min, and then the corresponding absorbance of the solution is measured at 475nm, wherein the absorbance is respectively expressed as A, B, C, D and the calculation formulas are as follows:

inhibition ratio of tyrosinase = [ (A-suction-B-suction) - (C-suction-D-suction) ]/(A-suction-B-suction) ×100%

The results obtained are as follows:

from the results, the composition provided by the invention has an effective inhibition effect on tyrosinase, the inhibition effect reaches more than 66.9%, and the effects larger than those of the comparative examples and the raw materials are reflected, so that the compound collocation of the raw materials of the composition can assist in synergy and comprehensively inhibit the formation of tyrosinase.

Post-inflammatory pigmentation removal experiments:

(1) The compositions obtained in examples 1-5 and comparative examples 1-6 were prepared into cream with cannabidiol, cannabis polysaccharide, retinol, hydroxydroxypenoside, ergothioneine and glabridin as the respective raw materials, and 1% arbutin as the control;

(2) The auxiliary agent is oil phase raw material caprylic capric triglyceride, the emulsifying agent is C14-22 alcohol (and C12-20 alkyl glucoside), and the solvent is deionized water. The preparation method comprises the following steps:

firstly, weighing 10g of caprylic/capric triglyceride and 1.5g of C14-22 alcohol (and C12-20 alkyl glucoside), heating to 85 ℃ for dissolution, adding a sample, stirring and dissolving until the mixture is uniformly phase A; (sample amount was 6.0 g)

And a second step of: 50g of the aqueous solution is weighed, heated to 85 ℃, added into the phase A, heated while stirring, emulsified and homogenized for 30min at a temperature of 85 ℃ and used as the main phase.

And a third step of: and adding a certain amount of water into the main phase, continuously stirring and homogenizing, and supplementing 100g of water to obtain the experimental paste.

(3) Subject selection: the people with multiple exposed parts and pigmentation with color spots after dermatitis can be light brown, dark brown, 180 people with black people, and partial sexes with age distribution of 18-45 years. The compositions obtained in examples 1-5 and comparative examples 1-6 and the pastes prepared from cannabidiol, cannabis polysaccharide, retinol, hydroxydroxypenside, ergothioneine and glabridin were equally divided into 18 groups of 10 persons each, and applied to the sites of inflammatory melanin precipitation, and the compositions were tested after cleansing the skin in the morning and evening, with the test amount of 0.5g each time. The usage is continued for 10 weeks. The size of the skin stain area using the first week and tenth week and the change in skin melanin MI value were measured, respectively. The results are shown in the following table:

the MI value indicates the melanin content in the skin, and the higher the measured value, the higher the pigment content, the lower the change rate of the MI value, and the better the melanin-lightening effect of the tested sample. From the above data, it can be seen that the effect of the paste obtained in example 1 on melanin desalination is optimal, the change rate of the color change area and MI after use is obviously lower than the change rate (P < 0.01) of one week after use, and the result is superior to that of comparative examples 1-6 and the raw material group, which shows that the invention obviously reduces the deposition of inflammatory melanin through the compounding and synergistic effect of six raw materials.

The applicant states that the cannabidiol-containing compositions of the present invention and their use are illustrated by the above examples, but the invention is not limited to, i.e. it is not meant that the invention must be practiced in dependence upon the above examples. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.

The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.

In addition, the specific features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described further.

Claims

1. A composition comprising cannabidiol, wherein the composition comprises cannabidiol, cannabis polysaccharide, retinol, hydroxyasiaticoside, ergothioneine, and glabridin.

2. The composition according to claim 1, wherein the composition comprises, in parts by weight, 0.8-1.2 parts of cannabidiol, 0.1-3 parts of cannabis polysaccharide, 0.1-5 parts of retinol, 0.2-2 parts of hydroxycentella asiatica glycoside, 0.5-2 parts of ergothioneine and 0.1-3 parts of glabridin.

3. The composition according to claim 2, wherein the composition comprises, in parts by weight, 0.8-1.2 parts of cannabidiol, 0.5-2 parts of cannabis polysaccharide, 0.1-2 parts of retinol, 0.5-1 part of hydroxycentella asiatica glycoside, 0.5-1.8 parts of ergothioneine and 0.1-2 parts of glabridin.

4. Use of a composition according to any one of claims 1-3 for the preparation of an anti-inflammatory drug.

5. Use of a composition according to any one of claims 1-3 for the preparation of an inhibitor of tyrosinase activity.

6. Use of a composition according to any one of claims 1-3 for the manufacture of a medicament for lightening melanin.

7. The use according to claim 6, wherein the melanin is caused by inflammatory pigmentation.

8. A medicament for lightening inflammatory hyperpigmented stains, comprising the composition of any one of claims 1-3.

9. A medicament for lightening inflammatory hyperpigmented spots as claimed in claim 8 wherein the medicament is in a form comprising any one of a cream, patch, spray, ointment, plaster, emulsion, spread or paste.

10. A medicament for lightening inflammatory pigmented spots according to claim 8 or 9, further comprising a pharmaceutically acceptable adjuvant comprising any one or a combination of at least two of a diluent, a solubilising agent, an emulsifier, a humectant, a thickener, a carrier or a filler;