Composition containing cannabidiol and/or cannabidivarol and application thereof in treatment of dysmenorrhea

Abstract

The present invention discloses a composition for preventing and/or treating woman dysmenorrhea; the composition includes cannabidiol and/or cannabidivarol, a penetration enhancer as well as a carrier; the mass ratio of the cannabidiol and/or the cannabidivarol to the penetration enhancer is 1:(0.1-0.8). The composition provided by the present invention can effectively relieve woman dysmenorrhea, and solve the problem of lackness of a composition of cannabidiol and/or cannabidivarol which can effectively prevent and/or treat woman dysmenorrhea in the prior art. Meanwhile, the composition provided by the present invention can also be used in preparation of a feminine hygiene product for preventing and/or treating woman dysmenorrhea.

Claims

1. A feminine hygiene product comprising a composition for treating dysmenorrhea, wherein the composition comprises cannabidiol and cannabidivarol, a penetration enhancer and a carrier, wherein a mass ratio of cannabidiol to cannabidivarol is (0.1-10):1.

2. The feminine hygiene product comprising the composition for treating dysmenorrhea according to claim 1, wherein the penetration enhancer is azone.

3. The feminine hygiene product comprising the composition for treating dysmenorrhea according to claim 1, wherein the mass ratio of the cannabidiol and/or cannabidivarol to the penetration enhancer is 1:(0.1-0.8).

4. The feminine hygiene product comprising the composition for treating dysmenorrhea according to claim 1, wherein the cannabidiol and cannabidivarol is extracted from a hemp plant, and the extraction site of the hemp plant is one or a combination of any two and more of hemp seeds, hemp leaves, hemp flowers, hemp stalk cores, and hemp roots at any ratio.

5. The feminine hygiene product comprising the composition for treating dysmenorrhea according to claim 1, wherein the composition is in a form of liquid, gel, ointment or patch.

6. The feminine hygiene product comprising the composition for treating dysmenorrhea according to claim 1, wherein the carrier is one or a combination of two or more selected from yarns, cotton threads or hemp fiber.

7. The feminine hygiene product comprising the composition for treating dysmenorrhea according to claim 1, wherein the carrier also contains one or a combination of two or more of a binder, a filler, a humectant, a crosslinking agent, a coloring agent, a pH regulator, and a preservative.

8. The feminine hygiene product comprising the composition for treating dysmenorrheal according to claim 7, wherein the binder is one or any combination of two or more selected from gelatin, sodium alginate, gum arabic, starch, methyl cellulose, carboxymethyl cellulose and its sodium salt, polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, carbomer, and polyacrylic acid and its sodium salt; the filler is one or any combination of two or more selected from zinc oxide, colloidal silicon dioxide, calcium carbonate, diatomaceous earth, and titanium dioxide; the humectant is any one or a combination of two or more selected from glycerol, propylene glycol, sorbitol, and polyethylene glycol; and the crosslinking agent is any one or a combination of two or more selected from calcium hydroxide, aluminum trichloride, aluminum glycinate, and EDTA disodium.

9. The feminine hygiene product comprising the composition for treating dysmenorrheal according to claim 1, wherein the mass ratio of the cannabidiol and/or cannabidivarol to the carrier in the composition is 1:(4-50).

10. The feminine hygiene product according to claim 1, wherein the feminine hygiene product is a sanitary towel, a sanitary napkin or a panty liner.

11. A method for treating dysmenorrhea using a feminine hygiene product for treating dysmenorrhea, wherein the method comprises applying a composition comprising cannabidiol and cannabidivarol, a penetration enhancer and a carrier, wherein a mass ratio of cannabidiol to cannabidivarol is (0.1-10):1, and a carrier comprising one or more of yarns, cotton threads or hemp fiber.

12. The method for treating dysmenorrhea using a feminine hygiene product according to claim 11, wherein the the mass ratio of the cannabidiol to the cannabidivarol is (0.1-10):1.

13. The method for treating dysmenorrheal using a feminine hygiene product according to claim 11, wherein the mass ratio of the cannabidiol and cannabidivarol to the penetration enhancer is 1:(0.1-0.8).

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

Example 1. Extraction of Cannabidiol

(1) (1) The raw materials hemp flowers, and leaves were washed to be clean and air dried;

(2) (2) The above-mentioned air-dried raw materials were pulverized to 40-mesh;

(3) (3) 95% ethanol with the amount being 8 times of the amount of the obtained powder was added into the obtained powder and cold extraction was conducted for 3 times, wherein cold extraction every time was conducted for 1 hour;

(4) (4) Extracts were mixed, and decolored; and

(5) (5) Concentration was conducted under reduced pressure to a relative density of 1.05;

(6) So as to obtain a cannabidiol extract, wherein the cannabidiol content, in percentage by mass, was 99.5%.

(7) It should be noted that, description such as “the amount being 8 times” in the present invention means that the volume of the used extraction solvent is 8 times of the mass of the extraction site, for example, if the mass of the extraction site of hemp is 1 g, the volume of the extraction solvent is 8 ml.

Example 2. Extraction of Cannabidivarol

(8) (1) Raw materials hemp flowers and leaves were washed to be clean and air dried;

(9) (2) The above-mentioned air-dried raw materials were pulverized to 40-mesh;

(10) (3) Absolute ethyl alcohol with the amount being 10 times of the amount of the obtained powder was added into the obtained powder in a mass-to-volume ratio, and cold extraction was conducted for 3 times, wherein cold extraction every time was conducted for 1 hour;

(11) (4) Extracts were mixed, decolored, and concentrated;

(12) (5) A chromatographic column was taken, the column was packed by using silica gel as a filler, and the extract was loaded onto the column and passed through the column, wherein the mobile phase was 80:20 of petroleum ether and diethyl ether, and the flow rate was 3.0 ml/min; and

(13) (6) The eluate containing a cannabidivarol component was collected, and the solvent was removed by rotary evaporation to obtain a cannabidiol extract, wherein the cannabidivarol content (in mass percent) was 97.5%.

Example 3. Preparation of an Externally Applied Patch for Preventing and/or Treating Woman Dysmenorrhea

(14) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was an externally applied drug in a form of patch, a backing layer is made of nonwoven fabric, a protective layer is made of release paper, in the drug reservoir layer, the mass ratio of cannabidiol to the penetration enhancer is 1:0.5, the penetration enhancer is ginger volatile oil, the carrier of the drug reservoir layer is polymeric hydrogel, the mass ratio of the cannabidiol to the carrier is 1:4, and the polymeric hydrogel was prepared by mixing sodium carboxymethylcellulose, glycerol, water, aluminium oxide well at a mass ratio of 10:30:40:0.1.

(15) Cannabidiol and ginger volatile oil were mixed well, and mixed with the polymeric hydrogel well, then the mixture was poured into a coater, the nonwoven fabric of the backing layer was evenly coated with the mixture, and the nonwoven fabric coated with the mixture was covered with the release paper of the protective layer to obtain the patch.

Example 4. Preparation of an Externally Applied Patch for Preventing and/or Treating Woman Dysmenorrhea

(16) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was an externally applied drug in a form of patch, a backing layer was made of nonwoven fabric, a protective layer was made of release paper, in the drug reservoir layer, the mass ratio of cannabidivarol to the penetration enhancer is 1:0.1, the penetration enhancer is peppermint volatile oil, the carrier of the drug reservoir layer was polymeric hydrogel, the mass ratio of the cannabidivarol to the carrier was 1:9, and the polymeric hydrogel was prepared by mixing sodium carboxymethylcellulose, propylene glycol, water, and calcium hydroxide well at a mass ratio of 7:25:30:0.2.

(17) Cannabidivarol and peppermint volatile oil were mixed well, and mixed with the polymeric hydrogel well, then the mixture was poured into a coater, the nonwoven fabric of the backing layer was evenly coated with the mixture, and the nonwoven fabric coated with the mixture was covered with the release paper of the protective layer to obtain the patch.

Example 5. Preparation of an Externally Applied Patch for Preventing and/or Treating Woman Dysmenorrhea

(18) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was an externally applied drug in a form of patch, a backing layer was made of nonwoven fabric, a protective layer was made of release paper, in the drug reservoir layer, the mass ratio of cannabidiol to cannabidivarol was 5:1, the mass ratio of a mixture of the cannabidiol and cannabidivarol to the penetration enhancer was 1:0.8, the penetration enhancer is propylene glycol, the carrier of the drug reservoir layer was polymeric hydrogel, the mass ratio of the mixture of the cannabidiol and cannabidivarol to the carrier was 1:15, and the polymeric hydrogel was prepared by mixing sodium carboxymethylcellulose, glycerol, water, and calcium hydroxide well at a mass ratio of 8:40:55:0.3.

(19) Cannabidiol and cannabidivarol were evenly mixed, and added into propylene glycol, stirred well, and then mixed with polymeric hydrogel well, then the mixture was poured into a coater, and the nonwoven fabric of the backing layer was evenly coated with the mixture, and the nonwoven fabric coated with the mixture was covered with the release paper of the protective layer to obtain the patch.

Example 6. Preparation of an Externally Applied Patch for Preventing and/or Treating Woman Dysmenorrhea

(20) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was an externally applied drug in a form of patch, a backing layer was made of nonwoven fabric, a protective layer was made of release paper, in the drug reservoir layer, the mass ratio of cannabidivarol to the penetration enhancer was 1:0.5, the penetration enhancer was azone, the carrier of the drug reservoir layer was a hot-melt pressure sensitive adhesive, the mass ratio of cannabidivarol to the carrier was 1:20, and the hot-melt pressure sensitive adhesive was prepared by weighing styrene-butadiene rubber, a tackifier (the tackifier is a mixture of glycerol ester of hydrogenated rosin with pentaerythritol ester of rosin at a mass ratio of 1:1) and squalane at a mass ratio of 2.8:3.3:2.1, conducting heating to melt the weighed materials, and conducting uniform mixing.

(21) Cannabidivarol and azone were mixed well, and mixed with the hot-melt pressure sensitive adhesive well, then the mixture was poured into a coater, and the nonwoven fabric of the backing layer was evenly coated with the mixture, and the nonwoven fabric coated with the mixture was covered with the release paper of the protective layer to obtain the patch.

Example 7. Preparation of an Externally Applied Patch for Preventing and/or Treating Woman Dysmenorrhea

(22) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was an externally applied drug in a form of patch, a backing layer was made of nonwoven fabric, a protective layer was made of release paper, in the drug reservoir layer, the mass ratio of cannabidiol to the penetration enhancer was 1:0.1, the penetration enhancer was azone, the carrier of the drug reservoir layer is a hot-melt pressure sensitive adhesive, the mass ratio of cannabidiol to the carrier was 1:25, and the hot-melt pressure sensitive adhesive was prepared by weighing styrene-butadiene rubber, a tackifier (the tackifier was a mixture of glycerol ester of hydrogenated rosin and pentaerythritol ester of rosin at a mass ratio of 1:1) and squalane at a mass ratio of 3.9:3.3:2.4, conducting heating to melt the weighed materials, and conducting uniform mixing.

(23) Cannabidiol and azone were mixed well, and mixed with the hot-melt pressure sensitive adhesive well, then the mixture was poured into a coater, and the nonwoven fabric of the backing layer was evenly coated with the mixture, and the nonwoven fabric coated with the mixture was covered with the release paper of the protective layer to obtain the patch.

Example 8. Preparation of an Externally Applied Patch for Preventing and/or Treating Woman Dysmenorrhea

(24) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was an externally applied drug in a form of patch, a backing layer was made of nonwoven fabric, a protective layer was made of release paper, in the drug reservoir layer, the mass ratio of drug cannabidiol to the penetration enhancer is 1:0.8, the penetration enhancer was azone, the carrier of the drug reservoir layer was a hot-melt pressure sensitive adhesive, the mass ratio of cannabidiol to the carrier was 1:30, and the hot-melt pressure sensitive adhesive was prepared by weighing styrene-butadiene rubber, a tackifier (the tackifier is a mixture of glycerol ester of hydrogenated rosin and pentaerythritol ester of rosin at a mass ratio of 1:1) and squalane at a mass ratio of 3.5:4.7:3.5, conducting heating to melt the weighed materials, and conducting uniform mixing.

(25) Cannabidiol and azone were mixed well, and mixed with the hot-melt pressure sensitive adhesive, then the mixture was poured into a coater, and the nonwoven fabric of the backing layer was evenly coated with the mixture, and the nonwoven fabric coated with the mixture was covered with the release paper of the protective layer to obtain the patch.

Example 9. Preparation of a Composition for Preventing and/or Treating Woman Dysmenorrhea and Using Hemp Fiber as a Carrier

(26) Preparation of a composition for preventing and/or treating woman dysmenorrhea was provided, wherein the carrier of the composition was hemp fiber, in the composition, the mass ratio of cannabidiol to the carrier was 1:50, in the composition, the penetration enhancer was azone, and the mass ratio of cannabidiol to azone was 1:0.8.

(27) Appropriate amount of ethanol was taken, and cannabidiol was dissolved in ethanol, and azone was added into ethanol, the above materials were stirred well, and hemp fiber was immersed in ethanol in which cannabidiol and azone were dissolved, the materials were allowed to stand for 1 hour, and the hemp fiber was taken out from ethanol, and air-dried in an aseptic environment at 16° C. for 3 hours, and the above-mentioned steps were repeated until ethanol was entirely immersed into the hemp fiber to obtain the composition.

Example 10. Preparation of a Sanitary Towel for Preventing and/or Treating Woman Dysmenorrhea

(28) (1) Preparation of a composition for preventing and/or treating woman dysmenorrhea was provided, wherein the carrier of the composition is hemp fiber, in the composition, the mass ratio of cannabidiol to the carrier is 1:45, in the composition, the penetration enhancer is azone, and the mass ratio of cannabidiol to azone is 1:0.7. Appropriate amount of ethanol was taken, and cannabidiol was dissolved in ethanol, and azone was added into ethanol, the above materials were stirred well, and the hemp fiber was immersed in ethanol in which cannabidiol and azone were dissolved, the materials were allowed to stand for 1 hour, and the hemp fiber was taken out from ethanol, and air dried at 16° C. in an aseptic environment for 3 hours, and the above-mentioned steps were repeated until ethanol was entirely immersed into the hemp fiber to obtain the composition.

(29) (2) A sanitary towel was prepared by using the composition containing hemp fiber prepared in the step (1), the sanitary towel was composed of an outer layer, an inner layer and an lower layer, the outer layer was made by weaving the composition containing hemp fiber prepared in the step (1), the inner layer of the sanitary towel was made of a cotton material, and the lower layer was made of a film material.

Example 11. Preparation of an Externally Applied Cream for Preventing and/or Treating Woman Dysmenorrhea

(30) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was a cream, in the cream, the mass ratio of cannabidiol to the penetration enhancer was 1:0.3, the penetration enhancer was ginger volatile oil, in the carrier, the oil phase was a mixture of lanolin, stearic acid, and liquid paraffin at a mass ratio of 1.6:2.5:1.8, in the carrier, the water phase was a mixture of glycerol, ethylparaben, carbomer at a mass ratio of 7.3:1:1, and the mass ratio of cannabidiol to the carrier was 1:40.

(31) Lanolin, stearic acid, and liquid paraffin were mixed well, heated to 65° C.-90° C., and fully dissolved to obtain an oil phase; glycerol, ethylparaben, carbomer and a part of water were mixed and heated to 65° C.-90° C. to obtain a water phase; the oil phase was added into the water phase, and stirred to obtain a cream carrier, and cannabidiol was added into the cream carrier, and stirred well, and the ginger volatile oil was added into the cream, and stirred well to obtain the externally applied cream.

Example 12. Preparation of an Externally Applied Cream for Preventing and/or Treating Woman Dysmenorrhea

(32) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was a cream, in the cream, the mass ratio of cannabidiol to the penetration enhancer was 1:0.5, the penetration enhancer was peppermint volatile oil, in the carrier, the oil phase was a mixture of vaseline, triethanolamine, stearic acid, and liquid paraffin at a mass ratio of 2:1.2:2.8:1.9, in the carrier, the water phase was a mixture of glycerol, ethylparaben, and carbomer at a mass ratio of 8:1.5:1.7, and the mass ratio of cannabidiol to the carrier was 1:50.

(33) Vaseline, triethanolamine, stearic acid, and liquid paraffin were mixed well, heated to 65° C.-90° C. and totally dissolved to obtain an oil phase; glycerol, ethylparaben, carbomer and a part of water were mixed and heated to 65° C.-90° C. to obtain a water phase; the oil phase was added into the water phase, and stirred to obtain a cream carrier, and cannabidiol was added into the cream carrier, and stirred well, and the peppermint volatile oil was added into the cream, and stirred well to obtain the externally applied cream.

Example 13. Preparation of an Externally Applied Liquid Liniment for Preventing and/or Treating Woman Dysmenorrhea

(34) An externally applied drug for preventing and/or treating woman dysmenorrhea was prepared, wherein the externally applied drug was a liquid externally applied drug, in the liquid externally applied drug, the mass ratio of cannabidiol to the penetration enhancer was 1:0.8, the penetration enhancer was azone, the carrier was a mixture of glycerol and ethanol at a mass ratio of 1:1, and the mass ratio of the cannabidiol to the carrier was 1:50.

(35) Cannabidiol was dissolved in a mixed liquor of glycerol and ethanol, and stirred well, then azone was added and stirred until a colorless and transparent liquid was formed to obtain a body surface externally applied liquid liniment.

Example 14. Influence of Compositions with Different Cannabidiol or Cannabidivarol Contents on a Rat Dysmenorrhea Model

(36) Experiment samples: patches containing cannabidiol and azone and the carrier at a mass ratio of 1:0.8:4, 1:0.8:25, and 1:0.8:50; patches containing cannabidivarol and azone and the carrier at a mass ratio of 1:0.8:4, 1:0.8:25, and 1:0.8:50.

(37) Experimental animals: female rats of 200-220 g.

(38) Experiment method: the patches containing cannabidiol or cannabidivarol and azone and the carrier at mass ratio of 1:0.8:4, 1:0.8:25, and 1:0.8:50 were cut into small patches of 3×3 cm.sup.2 ready for use, wherein in the patches of each group, the total dose of the composition of cannabidiol or cannabidivarol, azone and the carrier were the same.

(39) 70 healthy adult female rats were taken, the body weight was 210 g±8 g, and the rats were randomly divided into 7 groups, and the hairs on abdominal skin were shaved.

(40) The first group was a negative control group, in the rat abdomen patch, the composition containing cannabidiol or cannabidivarol, azone and the carrier was replaced with equal quantity of physiological saline;

(41) In the second group, in the rat abdomen patch, the mass ratio of cannabidiol to azone to the carrier was 1:0.8:4;

(42) In the third group, in the rat abdomen patch, the mass ratio of cannabidiol to azone to the carrier was 1:0.8:25;

(43) In the fourth group, in the rat abdomen patch, the mass ratio of cannabidiol to azone to the carrier was 1:0.8:50;

(44) In the fifth group, in the rat abdomen patch, the mass ratio of cannabidivarin to azone to the carrier was 1:0.8:4;

(45) In the sixth group, in the rat abdomen patch, the mass ratio of cannabidivarol to azone to the carrier was 1:0.8:25;

(46) In the seventh group, in the rat abdomen patch, the mass ratio of cannabidivarol to azone to the carrier was 1:0.8:50. The patch was changed every day, and continued to be applied for 4 days.

(47) The rats in each group were respectively injected subcutaneously (sc) with diethylstilbestrol, and subcutaneous injection was continued to be conducted for 4 days, and the daily dose was 8 mg/kg, so as to increase sensitivity of uteruses. In each group, on the 4th day, after 2 hours of administration, the rats were injected intraperitoneally with oxytocin at a dose of 2 IU/rat, to make rat uteruses shrink, and induce their writhing responses, the writhing number of every rat within subsequent 40 minutes was observed and recorded, and incidences of writhing were calculated. The recorded results were as shown in Table 1.

(48) Wherein, incidence of writhing (%)=writhing animal number in each group/experimental animal number in each group×100%.

(49) Experiment Results:

(50) As shown in Table 1, the patches in the second to the seventh groups had obvious relieving effects on rat dysmenorrhea-like response induced by oxytocin; the higher the content of cannabidiol or cannabidivarol, the more significant the patches were able to relieve the writhing response in rats, and the longer the response latency can be prolonged.

(51) TABLE-US-00001 TABLE 1 Results of the rat writhing experiment using compositions with different cannabidiol or cannabidivarol contents. Animal Writhing number Incidence of Groups number/group within 40 minutes writhing (%) First group 10 38.39 ± 11.03 100 Second group 10  9.64 ± 11.69 30 Third group 10 13.43 ± 9.65  50 Fourth group 10 16.73 ± 12.17 60 Fifth group 10 14.34 ± 10.73 40 Sixth group 10 17.22 ± 11.98 60 Seventh group 10 18.76 ± 10.91 60

Example 15. Influence of a Ratio of Cannabidiol to the Penetration Enhancer on Rat Dysmenorrhea Model

(52) Experiment samples: patches containing cannabidiol and azone at a mass ratio of 1:1, 1:0.8, 1:0.4, 1:0.1, and 1:0.05.

(53) Experimental animals: female rats of 200-220 g.

(54) Experiment method: patches containing cannabidiol and azone at a mass ratio of 1:1, 1:0.8, 1:0.4, 1:0.1, and 1:0.05 were cut into small patches of 3×3 cm.sup.2 ready for use, wherein in the patches of each group, the dose of cannabidiol were the same, and the mass ratio of cannabidiol to the carrier were all 1:10.

(55) 60 female rats with a body weight of 200-220 g were randomly divided into 6 groups, 10 rats in every group, and the hairs on abdominal skin were shaved.

(56) The first group was a negative control group, the rat abdomens were applied with patches of 3×3 cm.sup.2, wherein the patch prepared from a mixture of cannabidiol and azone was replaced with equal quantity of physiological saline;

(57) In a second group, the rat abdomens were applied with patches containing cannabidiol and azone at a mass ratio of 1:1;

(58) In a third group, the rat abdomens were applied with patches containing cannabidiol and azone at a mass ratio of 1:0.8;

(59) In a fourth group, the rat abdomens were applied with patches containing cannabidiol and azone at a mass ratio of 1:0.4;

(60) In a fifth group, the rat abdomens were applied with patches containing cannabidiol and azone at a mass ratio of 1:0.1;

(61) In a sixth group, the rat abdomens were applied with patches containing cannabidiol and azone at a mass ratio of 1:0.05.

(62) The patches were changed every day, and continued to be applied for 4 days.

(63) The rats in each group were respectively injected subcutaneously (sc) with diethylstilbestrol, and subcutaneous injection was continued to be conducted for 4 days, and the daily dose was 8 mg/kg, so as to increase sensitivity of uteruses. In each group, at the 4th day, after 2 h of administration, the rats were injected intraperitoneally with oxytocin at a dose of 2 IU/rat, to make the rat uteruses shrink, and induce their writhing responses, the writhing number of every rat within the subsequent 40 minutes was observed and recorded, and incidence of writhing was calculated. The recorded results were as shown in Table 2.

(64) Wherein, incidence of writhing (%)=writhing animal number in each group/experimental animal number in each group×100%.

(65) Experiment Results:

(66) As the results shown in Table 2, compared with the negative control group, the other groups had the advantages that the patches containing the mixture of cannabidiol and azone were all able to relieve the writhing response of the rats, especially the patches in the third group, the fourth group, and the fifth group were more able to significantly relieve the writhing response of the rats, which showed that when the mass ratio of cannabidiol to azone was 1:0.8, 1:0.4, and 1:0.1, the patches were able to better relieve dysmenorrhea of the rats.

(67) TABLE-US-00002 TABLE 2 Experiment results of rat writhing experiment using the compositions with different penetration enhancer contents. Writhing number Incidence of writhing Groups within 40 minutes (%) First group 38.39 ± 11.03 100 Second group 22.85 ± 10.34 70 Third group 13.43 ± 9.65  50 Fourth group 10.62 ± 9.42  40 Fifth group 11.12 ± 10.35 40 Sixth group 26.96 ± 10.71 70

Example 16. Influence of the Type of the Penetration Enhancer on Rat Dysmenorrhea Model

(68) Experiment samples: a patch with a mass ratio of cannabidiol to azone being 1:0.8; a patch with a mass ratio of cannabidiol to ginger volatile oil being 1:0.8; a patch with a mass ratio of cannabidiol to peppermint volatile oil being 1:0.8; a patch with a mass ratio of cannabidiol to DMI being 1:0.8.

(69) Experimental animals: female rats of 200-220 g.

(70) Experiment Method:

(71) The patch containing cannabidiol and azone at a mass ratio of 1:0.8; the patch containing cannabidiol and ginger volatile oil at a mass ratio of 1:0.8; the patch containing cannabidiol and peppermint volatile oil at a mass ratio of 1:0.8; and the patch containing cannabidiol and DMI at a mass ratio of 1:0.8 were cut into small patches of 3×3 cm.sup.2 ready for use, wherein in the patches of each group, the doses of cannabidiol were the same, and the mass ratio of cannabidiol to the carrier were all 1:10.

(72) 50 female rats with a body weight of 200-220 g were randomly divided into 5 groups, 10 rats in every group, and the hairs on abdominal skin were shaved.

(73) The first group was a negative control group, the rat abdomens were applied with patches of 3×3 cm.sup.2, wherein the patch prepared from a mixture of cannabidiol and the penetration enhancer was replaced with equal amount of physiological saline;

(74) In the second group, the rat abdomens were applied with patches containing cannabidiol and azone at a mass ratio of 1:0.8;

(75) In the third group, the rat abdomens were applied with patches containing cannabidiol and ginger volatile oil at a mass ratio of 1:0.8;

(76) In the fourth group, the rat abdomens were applied with patches containing cannabidiol and peppermint volatile oil at a mass ratio of 1:0.8;

(77) In the fifth group, the rat abdomens were applied with patches containing cannabidiol and DMI at a mass ratio of 1:0.8.

(78) The patches were changed every day, and continued to be applied for 4 days.

(79) The rats in each group were respectively subcutaneously injected (sc) with diethylstilbestrol, and subcutaneous injection was continued to be conducted for 4 days, and the daily dose was 8 mg/kg (in terms of cannabidiol), so as to increase sensitivity of uteruses. In each group, on the 4th day, after 2 hours of administration, the rats were injected intraperitoneally with oxytocin at a dose of 2 IU/rat, to make the rat uteruses shrink, and induce their writhing responses, the writhing number of every rat within subsequent 40 minutes was observed and recorded, and incidence of writhing was calculated. Results are as shown in Table 3, wherein incidence of writhing (%)=writhing animal number in each group/experimental animal number in each group×100%.

(80) Experiment Results:

(81) As the results shown in Table 3, compared with the negative control group, the other groups had the advantages that the patches containing a mixture of cannabidiol and the penetration enhancer were able to significantly relieve the writhing response of the rats, especially the patches in the second group were able to more significantly relieve the writhing response of the rats, which showed that the patches prepared from cannabidiol and azone were able to better relieve dysmenorrhea of the rats.

(82) TABLE-US-00003 TABLE 3 Experiment results of the rat writhing experiment using different types of penetration enhancers. Writhing number Incidence of writhing Groups within 40 minutes (%) First group  38.39 ± 11.03 100 Second group 13.43 ± 9.65 40 Third group  16.87 ± 10.35 50 Fourth group 17.69 ± 9.28 60 Fifth group 16.17 ± 9.59 50

Example 17. Influence of a Content Ratio of Cannabidiol to Cannabidivarol in the Composition on Rat Dysmenorrhea Model

(83) Experiment samples: patches containing cannabidiol, cannabidivarol, azone and the carrier, in the patches, the mass ratio of cannabidiol and cannabidivarol to azone to the carrier was 1:0.8:10, and in each group, the mass ratio of cannabidiol to cannabidivarol were 1:0.1, 1:0.2, 1:1, and 1:10, respectively.

(84) Experimental animals: female rats of 200-220 g.

(85) Experiment Method:

(86) The patches of each group in which the mass ratio of cannabidiol to cannabidivarol in the composition was 1:0.1, 1:0.2, 1:1, and 1:10, respectively were cut into small patches of 3×3 cm.sup.2 ready for use, wherein in the patches of each group, the total dose of cannabidiol and cannabidivarol was the same.

(87) 40 female rats with a body weight of 200-220 g were randomly divided into 4 groups, 10 rats in every group, and the hairs on abdominal skin were shaved.

(88) In the first group, the rat abdomens were applied with patches containing cannabidiol and cannabidivarol with a mass ratio of 1:0.1;

(89) In the second group, the rat abdomens were applied with patches containing cannabidiol and cannabidivarol with a mass ratio of 1:0.2;

(90) In the third group, the rat abdomens were applied with patches containing cannabidiol and cannabidivarol with a mass ratio of 1:1;

(91) In fourth group, the rat abdomens were applied with patches containing cannabidiol and cannabidivarol with a mass ratio of 1:10.

(92) The patches were changed every day, and continued to be applied for 4 days.

(93) The rats in each group were respectively injected subcutaneously (sc) with diethylstilbestrol, and subcutaneous injection was continued to be conducted for 4 days, and the daily dose was 8 mg.Math.kg-1 (in terms of cannabidiol), so as to increase sensitivity of uteruses. In each group, on the 4th day, after 2 hours of administration, the rats were injected intraperitoneally with oxytocin at a dose of 2 IU/rat, to make the rat uteruses shrink, and induce their writhing responses, the writhing number of each rat within subsequent 40 minutes was observed and recorded, and incidence of writhing was calculated. The results are as shown in Table 4, wherein incidence of writhing (%)=writhing animal number in each group/experimental animal number in each group×100%.

(94) Experiment Results:

(95) As the results shown in Table 4, the patches containing cannabidiol and cannabidivarol at different ratios have obvious relieving effects on the rat dysmenorrhea-like response caused by oxytocin, but when the content ratio of cannabidiol in composition is higher, the patches were more able to relieve the writhing response of the rats, especially when the mass ratio of cannabidiol and cannabidivarol is 1:0.2, the patches have the best effect.

(96) TABLE-US-00004 TABLE 4 Experiment results of the rat writhing experiment using compositions containing cannabidiol and cannabidivarol at a different ratio. Writhing number Incidence of writhing Groups within 40 minutes (%) First group 14.18 ± 10.32 40 Second group 12.79 ± 11.98 40 Third group 15.47 ± 12.98 50 Fourth group 16.08 ± 10.55 50

(97) The above-mentioned examples do not limit the present invention in any way, the technical solutions obtained in a manner of equivalent substitution or equivalent alternation all fall in the protection scope of the invention.