WO2021177940A1 - Compositions à base de gel de menthol et de cannabinoïdes, timbres et procédés - Google Patents

Compositions à base de gel de menthol et de cannabinoïdes, timbres et procédés Download PDF

Info

Publication number
WO2021177940A1
WO2021177940A1 PCT/US2020/020722 US2020020722W WO2021177940A1 WO 2021177940 A1 WO2021177940 A1 WO 2021177940A1 US 2020020722 W US2020020722 W US 2020020722W WO 2021177940 A1 WO2021177940 A1 WO 2021177940A1
Authority
WO
WIPO (PCT)
Prior art keywords
menthol
amount
hydrogel
transdermal
transdermal analgesic
Prior art date
Application number
PCT/US2020/020722
Other languages
English (en)
Inventor
Babak Ghalili
Emma GHALILI
Original Assignee
Babak Ghalili
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Babak Ghalili filed Critical Babak Ghalili
Priority to PCT/US2020/020722 priority Critical patent/WO2021177940A1/fr
Publication of WO2021177940A1 publication Critical patent/WO2021177940A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)

Definitions

  • compositions including active agents such as cannabinoids and menthol.
  • Hydrogels can be used as a vehicle for the delivery of drugs and other therapeutically active agents. They refer to a network of hydrophilic polymer chains that are generally found as a colloidal gel in which water is the dispersion medium. Hydrogels are highly absorbent (they can contain over 99.9% water) natural or synthetic polymers and can also possess a degree of flexibility very similar to natural tissue, due to their significant water content ("Terminology of polymers and polymerization processes in dispersed systems (IUPAC Recommendations 2011)". Pure and Applied Chemistry 83 (12): 2229-2259. 2011).
  • FIG. 1 is a perspective view of an embodiment of the present disclosure
  • FIGS. 2A and 2B are perspective views of other embodiments of the present disclosure.
  • FIGS. 3 A to 3F illustrate an exemplary implementation of the aspects of the disclosed embodiments; and [0008] FIGS. 4A and 4B illustrate perspective and cross-sectional views of an exemplary packaging embodiment of the present disclosure.
  • a transdermal analgesic hydrogel device includes a surface to be applied to the skin of a mammal, the surface having an area ranging in size from about 9 cm 2 to about 256 cm 2 ; water in an amount of from about 70 wt% to about 95 wt%; a biocompatible polymer in an amount of from about 0.5 wt% to about 5 wt %; a polyalcohol in an amount of from about 1 wt% to about 5 wt%; at least one cannabinoid is in an amount of from about 0.1 wt% to about 10 wt and menthol is in an amount of from about 1 wt% to about 10 wt %, wherein the menthol is included in a stabilized menthol composition comprising menthol and at least one menthol stabilizer compound including undecylenic acid methyl ester, undecylenic acid or a salt of undecy
  • a transdermal analgesic hydrogel patch for topical application to the skin of a mammal.
  • the transdermal analgesic hydrogel patch includes water in an amount of from about 70 wt% to about 95 wt%; carageenan in an amount of from about 0.5 wt% to about 5 wt %; glycerin in an amount of from about 1 wt% to about 5 wt%; full spectrum hemp oil in an amount of from about 0.1 wt% to about 10 and menthol in an amount of from about 1 wt% to about 10 wt %, wherein the menthol is included in a stabilized menthol composition comprising menthol and at least one menthol stabilizer compound including undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid.
  • a method of treating pain or inflammation in a body part or portion thereof of a mammal using a transdermal hydrogel patch including a unit dose formulation including water in an amount of from about 70 wt% to about 95 wt%; carageenan in an amount of from about 0.5 wt% to about 5 wt %; glycerin in an amount of from about 1 wt% to about 5 wt%; full spectrum hemp oil in a unit dose amount of from about 2 mg. to about 195 mg; and menthol in a unit dose amount of from about 2 mg.
  • the method includes administering the transdermal hydrogel patch to a body part of the mammal.
  • % percents by weight based upon a total weight of 100% end composition weight.
  • 10% by weight means that the component constitutes 10 wt. parts out of every 100 wt. parts of total composition.
  • pharmaceutically acceptable means that which is useful in preparing a pharmaceutical composition that is generally non-toxic and is not biologically undesirable and includes that which is acceptable for veterinary use and/or human pharmaceutical use.
  • topically acceptable means the compound, substance or device may be administered to or onto the surface of a patient, including the skin or other accessible tissues, without substantial harmful effects to the body part and/or its surfaces.
  • compositions including hydrous hydrogel compositions and hydrous hydrogel composition patches for the delivery of an active agent(s).
  • the aspects of the present disclosure also relate to processes for the preparation of, intermediates used in the preparation of, compositions (e.g., pharmaceutical, medical device cosmetic, industrial) containing and the uses of such hydrous hydrogels in the treatment of disorders or application of specified agents to a skin surface.
  • compositions comprising an active agent (including acceptable salt thereof) pharmaceutical composition. Accordingly, in one embodiment, the present disclosure relates to a pharmaceutical composition comprising an active agent, a pharmaceutically acceptable carrier and, optionally, additional medicinal or pharmaceutical agent(s).
  • Active agents include pharmaceutical agents such as analgesics, decongestants, bronchodilators and other antiasthmatic agents, cardiovascular agents such as beta-blockers, ACE inhibitors, diuretics, antithrombics, etc., diabetic agents, antihistamines, anesthetics, antifungals, antinauseants, antiemetics, antibacterial agents, antifungal agents, corticosteroids, neurological agents, anti-inflammatories, vaccines, biological agents (such as Humera, Enbrel and Remicade), wound healing agents and anticonvulsants.
  • Vitamins are a particular embodiment of an active agent.
  • the concentration of the active ingredient in the gel base is, of course, dependent on the identity of the active agent, the condition and patient being treated and the potency desired.
  • formulations of the present disclosure are also useful in the fields of human medicine for the administration of active agents to people (i.e., human patients) and veterinary medicine for the administration of active agents to pets and farm animals.
  • compositions used to relieve pain i.e., analgesics
  • methods of making such compositions and methods of using such compositions including topically applied (e.g., to skin or another body part) compositions including pharmaceutical compositions, including analgesic and/or anti-inflammatory pharmaceutical compositions for the treatment of pain and/or inflammation, that contain a pharmaceutically effective amount of a pharmaceutically acceptable and effective cannabinoid, menthol and a pharmaceutically acceptable carrier, such as for example, a hydrous hydrogel material, vehicle or carrier.
  • compositions may also include, for example, analgesic and/or anti-inflammatory pharmaceutical compositions for the treatment of pain and/or inflammation that contain a pharmaceutically effective amount of a pharmaceutically acceptable and effective cannabinoid, menthol and a pharmaceutically acceptable carrier, such as for example, a hydrous hydrogel material, material or carrier.
  • analgesic and/or anti-inflammatory pharmaceutical compositions for the treatment of pain and/or inflammation that contain a pharmaceutically effective amount of a pharmaceutically acceptable and effective cannabinoid, menthol and a pharmaceutically acceptable carrier, such as for example, a hydrous hydrogel material, material or carrier.
  • the combination of cannabinoid and menthol into a single therapeutic composition can provide improved and better focused delivery of the actives to a patient than separately applying the cannabinoid and menthol separately (to different areas of the body or layered one on top of another) without the hydrous hydrogel vehicle.
  • compositions such as, for example, embodiments of the present disclosure, include products and compositions, for example, hydrous hydrogel products and compositions (e.g., patches including hydrous gel patches and hydrous hydrogel patches) including products of a mass of hydrogel composition in a desired size, shape and weight which, in the ordinary course of usage, can be placed topically on a body part (e.g., arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them) for purposes of local and/or systemic administration of particular therapeutic agents for a time sufficient to be effective for purposes of therapeutic activity to the body part and tissues thereof or other tissues remote from the application site in order to provide relief from the malady being suffered (e.g., pain relief though an analgesic and/or anesthetic effect) including a malady of the body part (e.g., pain and/or inflammation) to which the products and compositions of the present disclosure can be directly applied for relief.
  • a body part e.g., arm,
  • Embodiments of the present disclosure may be delivered for local or systemic administration to a body part of a person to be treated with the embodiment, for example, a body or skin surface thereof by placing an embodiment of the present disclosure on a body part or skin surface thereof, for example, a knee, leg, back of hand, arm, lower back,, upper back, shoulder and forehead, in active agent-transmitting relation thereto, the active agents being cannabinoid, for example, a phytocannabinoid or full spectrum hemp oil, and menthol.
  • an embodiment of the present disclosure may be incorporated into a delivery system, such as a unit dose delivery system or device (e.g. a "patch.” ").
  • the delivery system, device or “patch” can be of a suitable size and shape to fit against a body part so as to be applied to the skin surface thereof.
  • a suitable size for example, is illustrated in FIG. 1 which can include the shape of a square or rectangle 100 or other polygon shape (including, e.g., triangle, pentagon, hexagon, etc.) with surface areas 102 and 104 (on opposing sides) and the dimensions of sides 106, 107, 110 and 112, each ranging in length 114, 116, 118 and 120, respectively ranging from about 3 cm to about 16 cm including each surface area ranging from about 9 cm 2 to about 256 cm 2 , about 4.2 cm to about 6.5 cm including each surface area ranging from about 18 cm 2 to about 42 cm 2 , about 10 cm to about 14 cm including each surface area ranging from about 100 cm 2 to about 196 cm 2 and about 12 cm to about 16 cm including each surface area ranging from about 144 cm 2 to about 256 cm 2 .
  • embodiments could include patches with sides 106, 107, 110 and 112, each ranging in length 114, 116, 118 and 120, respectively, that are about 6.5 cm.
  • x about 4.2 cm surface area about 27.3 cm 2
  • 10 cm x about 14 cm surface area about 140 cm 2
  • 12 cm x about 16 cm surface area about 192 cm 2 .
  • Thickness 122 can range from about 0.05 cm to about 0.5 cm, about 0.05 cm to about 0.1 cm, about 0.05 cm to about 0.07 cm, about 0.0508 to about 0.06604 cm. Volumes of the patches can range from about 0.45 ml to about 128 ml, about 0.45 ml to about 25.6 ml, about 0.45 ml to about 18 ml, about 0.4572 ml. to about 17 ml, in keeping with the above patch dimensions.
  • the above referenced embodiments that include patches with a surface area 27.3 cm 2 based on the above ranges of thickness could have volumes ranging from about 1.4 ml to about 13.7 ml, about 1.4 ml to about 2.73 ml, 1.4 ml to about 1.9 ml, about 1.386 ml to about 1.803 ml; a surface area 140 cm 2 based on the above ranges of thickness could have volumes ranging from about 7 ml to about 70 ml, about 7 ml to about 14 ml, 7 ml to about 9.8 ml, about 7.112 ml to about 9.296 ml; and a surface area 192 cm 2 based on the above ranges of thickness could have volumes ranging from about 9.6 ml to about 96 ml, about 9.6 ml to about 19.2 ml, 9.6 ml to about 13.4 ml, about 0.754 ml to about 12.680 ml.
  • a square would have sides 105, 107, 110 and 112 approximately equal in dimensions while a rectangle would have sides 106 and 110 approximately equal in dimensions along with sides 107 and 112 approximately equal, but the dimensions of sides 106 and 110 may not always be equal to the dimension of sides 107 and 112. In other embodiments, the dimensions of any one of sides 106, 107, 110 and 112 may be equal to the dimensions of the other sides.
  • FIG. 2A Other embodiment shapes can also include a circle 200 illustrated in FIG. 2A having a generally circular shape with surface areas 202 and 204 on opposing sides thereof or an ellipse 206 illustrated in FIG. 2B and with surface areas 208 and 210 on opposing sides thereof.
  • the thickness 216 in circle 200 in FIGS. 2A and thickness 218 ellipse 206 in FIG. 2B can range from about 0.05 cm to about 0.5 cm, about 0.05 cm to about 0.1 cm, about 0.05 cm to about 0.07 cm, about 0.0508 to about 0.06604 cm.
  • Embodiments of the present disclosure are intended to be placed on the skin surface of a body part or body parts or portions thereof where a person is experiencing pain and/or inflammation resulting from, for example, injury or other physical diseases, stresses or conditions.
  • FIGS. 3 A to 3F Non-limiting exemplary embodiments showing possible placement are illustrated in FIGS. 3 A to 3F.
  • FIGS. 3 A and 3B show a top view and side view, respectively, of an arm 300 including a hand 302, wrist 304, forearm 306, elbow area 307 and upper arm 308.
  • One of the embodiments of the present disclosure 310 can be positioned against the hand 302 at 312.
  • An alternative is an embodiment of the present disclosure 314 can be positioned against the wrist 304 at 316.
  • An alternative is an embodiment of the present disclosure 318 can be positioned against the forearm 306 at 320.
  • An alternative is an embodiment of the present disclosure 319 can be positioned against the lower part of the forearm 306 at 321.
  • An alternative is an embodiment of the present disclosure 322 can be positioned against the elbow area 307 at 324 .
  • An alternative is an embodiment of the present disclosure 326 can be positioned against the upper arm 308 at 328.
  • FIGS. 3C and 3D show a side view and front view, respectively, of a leg 330 including a foot 332, ankle area 334, calf 336, knee area 338 and upper leg 340.
  • One of the embodiments of the present disclosure 342 can be positioned against the front of the ankle area 334 at 344.
  • An alternative is an embodiment of the present disclosure 346 can be positioned against the side of the ankle area 334 at 348.
  • An alternative is an embodiment of the present disclosure 350 can be positioned against the back of the ankle area 334 (e.g. against the Achilles tendon) at 352.
  • An alternative is an embodiment of the present disclosure 354 can be positioned against the side of the back of the calf 336 at 356.
  • An alternative is an embodiment of the present disclosure 358 can be positioned against the knee area 338 at 360.
  • FIG. 3E shows a rear view of an upper torso 368 including back 370, arms 372, shoulder area 374, spinal/backbone area 376 and neck 378.
  • One of the embodiments of the present disclosure 380 can be positioned against the lower region of the back 370 adjacent the spinal/backbone area 376 at 382.
  • An alternative is an embodiment of the present disclosure 384 can be positioned against the upper region of the back 370 adjacent the spinal/backbone area 376 at 386.
  • An alternative is an embodiment of the present disclosure 388 can be positioned against the back of the neck 378 (e.g. against the spinal/backbone area 376) at 390.
  • An alternative is an embodiment of the present disclosure 391 can be positioned against the upper area of the shoulder area 374 at 392.
  • An alternative is an embodiment of the present disclosure 393 can be positioned against the lower area of the shoulder area 374 at 394.
  • FIG. 3F shows a front view of a head 395 including a forehead 396.
  • One of the embodiments of the present disclosure 397 can be positioned against the forehead 396 at 398.
  • all surfaces of the embodiments of the present disclosure can be applied to the skin surface of body parts or portions thereof to administer the agents included therein (e.g., CBD and menthol) for transdermal delivery into and through the tissues of the skin surface to bring about the intended local and/or systemic effect
  • the largest surfaces e.g., surface areas 102 and 104 in FIG.l, in FIG. 2A with surface areas 202 and 204 and in FIG. 2B and with surface areas 208 and 210) should preferably be placed against those skin surfaces including the embodiments of FIGS. 3 A to 3F.
  • Non-limiting examples of injuries or other physical diseases or conditions causing pain and/or inflammation for which embodiments of the present disclosure can be used to reduce or lessen the pain and/or inflammation can include arthritis conditions (e.g., osteo, rheumatoid, psoriatic, fibromyalgia, etc.), head pain (e.g., concussion, head ache, migraine), orthopedic injuries or conditions (e.g., bone fracture or break; dislocated joint or bone; torn, stressed or strained ligament or tendon; bruising or trauma to tissue; back or spinal pain or herniated disc; tendonitis; gout, bursitis), muscles aches and pains (e.g., from stress and physical exertion) and post-surgery recovery (e.g., recovery from orthopedic surgery to repair a broken bone, back condition such as herniated disk or tom ligament, orthoscopic surgery, .
  • arthritis conditions e.g., osteo, rheumatoid, p
  • the hydrogel compositions of the present disclosure may also include an adhesive composition on one side thereof (e.g., one of the surface areas of the above embodiments).
  • the hydrogel adhesive composition may be cast or extruded onto a backing layer or release liner and once the backing layer or release liner is removed will serve as the skin-contacting face of the system and act as an active agent reservoir.
  • the hydrogel composition may be used as an active agent reservoir within the interior of such a system, with a conventional skin adhesive laminated thereto to affix the system to a surface of the body part of a patient, the body part that is experiencing pain and/or inflammation.
  • the cannabinoid for example, full spectrum hemp oil
  • Cannabinoids are an active agent and a class of chemical compounds that can be derived from plants (phytocannabinoids) or synthetically produced. Cannabinoids can have local and systemic analgesic, pain relieving, pain treating and anti-inflammatory therapeutic properties. Cannabinoids may also have other medical benefits and/or be useful in treating other medical conditions including, for example, reduction of anxiety and depression, reduction of symptoms like nausea, vomiting and pain related to cancer treatments, reduction of acne, protection of the neural system and benefits for the heart and circulatory system by the lowering of blood pressure. Cannabinoids can also have therapeutic value as a nutrient and can be included in composition and method embodiments of the present disclosure in an effective amount to perform that function.
  • phytocannabinoids examples include Cannabidiol (CBD) including, for example, CBD oil, Cannabinol (CBN) and tetrahydrocannabinol (THC), the latter being a known psychotropic compound and the first two being non-psycho tropic.
  • CBD Cannabidiol
  • CBN Cannabinol
  • THC tetrahydrocannabinol
  • Cannabis and hemp plants can exhibit wide variation in the quantity and type of cannabinoids they produce. Selective breeding of the plants can be used to control the genetics of plants and modify the cannabinoids produced by the plant. For example, there are strains that are used as fiber (commonly called hemp) and, as a result, have been bred such that they are low in psychoactive chemicals like THC.
  • Such strains e.g., hemp
  • cannabinoids included herein have minimal levels of THC (less than 0.3%).
  • topical, transdermal and/or pharmaceutically effective cannabinoids include CBD (for example, full spectrum hemp oil).
  • Cannabinoid including, for example, phytocannabinoids including CBD, can be in an amount of about 0.1 wt% to about 10 wt %, 0.1 wt% to about 1 wt %, about 0.5 wt% to about 6 wt%, about 2 wt%, about 2.1 wt%, about 4 wt%.
  • CBD can be in an amount of 0.1 wt% to about 10 wt%, about 0.5 wt% to about 5 wt%, about 0.5 wt% to about 2 wt% %, about 2 wt%, about 2.1 wt%, about 4 wt%.
  • Full spectrum CBD or hemp oil can be in an amount of about 0.1 wt% to about 10 wt %, 0.1 wt% to about 1 wt %, about 0.5 wt% to about 6 wt%, about 2 wt%, about 2.1 wt%, about 4 wt%.
  • Unit dosage formulations of the embodiments of the present disclosure can include cannabinoid, for example, a phytocannabinoid (including for example, CBD) in the amount of about 2 mg. to about 195 mg., about 14 mg. to about 100 mg., about 14 mg. to about 80 mg., about 70 mg. to about 195 mg., about 10 mg. to about 15 mg, about 70 mg. to about 80 mg, about 1900 mg. to about 195 mg, about 14 mg, about 77 mg, about 193 mg.
  • Unit dosage formulations of the embodiments of the present disclosure can include CBD in the amount of about 2 mg. to about 195 mg., about 14 mg. to about 100 mg., about 14 mg. to about 80 mg., about 70 mg. to about 195 mg., about 10 mg.
  • Unit doses of full spectrum hemp oil can include an amount of about 2 mg. to about 195 mg., about 14 mg. to about 100 mg., about 14 mg. to about 80 mg., about 70 mg. to about 195 mg., about 10 mg. to about 15 mg, about 70 mg. to about 80 mg, about 1900 mg. to about 195 mg, about 14 mg, about 77 mg, about 193 mg.
  • Unit dosage formulations of the embodiments of the present disclosure can include cannabinoid, for example, a phytocannabinoid (including for example, CBD) or full spectrum hemp oil in the amount of about 5 mg./ml.
  • Unit dosage formulations of the embodiments of the present disclosure can include CBD in the amount of about 1 mg./ml. to about 50 mg./ml, about 5 mg./ml. to about 40 mg./ml., about 5 mg./ml. to about 20 mg./ml., about 9 mg./ml to about 16 mg./ml., about 9 mg./ml., about 15 mg./ml.
  • Unit dosage formulations of the embodiments of the present disclosure can include CBD in the amount of about 1 mg./ml. to about 50 mg./ml, about 5 mg./ml. to about 40 mg./ml., about 5 mg./ml. to about 20 mg./ml., about 9 mg./ml to about 16 mg./ml., about 9 mg./ml., about 15 mg./ml.
  • Unit dosage formulations of the embodiments of the present disclosure can include full spectrum CBD oil in an amount of about 5 mg./ml. to about 40 mg./ml., about 5 mg./ml. to about 20 mg./ml., about 9 mg./ml to about 16 mg./ml., about 9 mg./ml., about 15 mg./ml.
  • Unit dosage formulations of the embodiments of the present disclosure can include cannabinoid, for example, a phytocannabinoid (including for example, CBD) in the amount per unit of surface area (e.g., surface areas 102 and 104 in FIG.l, in FIG. 2A with surface areas 202 and 204 and in FIG.
  • cannabinoid for example, a phytocannabinoid (including for example, CBD) in the amount per unit of surface area (e.g., surface areas 102 and 104 in FIG.l, in FIG. 2A with surface areas 202 and 204 and in FIG.
  • Unit dosage formulations of the embodiments of the present disclosure can include CBD in the amount of about 0.1 mg./cm 2 to about 2 mg./cm 2 , about 0.5 mg./cm 2 to about 1 mg./cm 2 , about 0.5 mg./cm 2 to about 0.6 mg./cm 2 , about 0.5 mg./cm 2 , about 0.53 mg./cm 2 , about 0.5 mg./cm 2 , about 1 mg./cm 2 .
  • Unit dosage formulations of the embodiments of the present disclosure can include full spectrum CBD oil in an amount of about 0.1 mg./cm 2 to about 2 mg./cm 2 , about 0.5 mg./cm 2 to about 1 mg./cm 2 , about 0.5 mg./cm 2 to about 0.6 mg./cm 2 , about 0.5 mg./cm 2 , about 0.53 mg./cm 2 , about 0.5 mg./cm 2 , about 1 mg./cm 2 .
  • An effective amount of cannabinoid includes an analgesic, pain relieving, pain treating or anti-inflammatory amount of cannabinoid.
  • Cannabinoids for example, CBD can have a local and/or a systemic effect and may reduce pain imparting and regulating the endocannabinoid (neurotransmitter of the nervous system) receptor activity.
  • the subsequent body functions that may be regulated include pain, sleep, appetite and immune system response (through, at least, in part, by reducing inflammation).
  • cannabinoid refers to one or more cannabinoids or cannabinoid compounds or oils or extracts from plants (for example, hemp including hemp oil and full spectrum CBD or full spectrum hemp oil, Cannabis sativa seed oil, etc.) that include one or a plurality of phytocannabinoids.
  • Full spectrum hemp oil is oil derived from the entire plant except the flower (which contains THC) and can have over 85 phytocannabinoids which can have a positive synergistic effect as compared to compositions having fewer cannabinoids. There may also be benefits to other components of it (e.g., terpenes). Such benefits and effect may include faster penetration and/or permeation of the therapeutic components thereof.
  • Full spectrum hemp oil can include full spectrum hemp oil that has been purified to include less than the below stated amounts of one or more of the following impurities:
  • Aflatoxins Bl, 82, Gl, G2 (fats, oils, lecithin, egg powder): ⁇ 0.1 pg/kg of each of Aflatoxin Bl, Aflatoxin B2, Aflatoxin Gl and Aflatoxin G2, Sum of all positive Aflatoxins ⁇ 0.4 pg/kg.
  • GlyphosatelAMPAiGlufosinate ⁇ 0.1 mg/kg of each of Glufosinate, Glyphosate and Aminomethylphosphonic acid (AMP A)
  • Embodiments of the present disclosure may also optionally include an effective amount of THC and other forms of THC such as THCA, THCV, delta-8 THC,delta-9 THC etc.
  • Unit dosage formulations of the embodiments of the present disclosure can include THC in the amount of about 0.1 mg. to about 10 mg., about 1 mg. to about 10 mg., about 4 mg. to about 6 mg. about 5 mg.
  • THC may relieve stress and be a sleeping aid.
  • Menthol is an active agent and an organic compound that can be made synthetically or obtained from mint oils such as com mint and peppermint.
  • menthol can have anesthetic (e.g., local) by, for example, blocking nerve signal transmission) and counterirritant properties as well as anti-inflammatory properties (e.g., systemic and local) as well as a cooling effect when administered topically to a patient.
  • menthol is a vasodilator that can accelerate the transport of active in the circulatory system.
  • the action of local anesthetics can restrict to the site of application and rapidly reverses upon diffusion from the site of action in the nerve. Local anesthetics can also serve an important function in providing peripheral pain relief.
  • Topical administration of pain-relieving anesthetics can provide important advantages over systemic or local, non-topical administration.
  • Menthol can be in an amount of about 1 wt% to about 10 wt %, about 5 wt% to about 10 wt%, about 5 wt %, about 6 wt%, about 8 wt%.
  • Unit dosage formulations of the embodiments of the present disclosure can include menthol in the amount of about 2 mg. to about 400 mg., about 30 mg. to about 40 mg., about 210 mg. to about 220 mg., about 380 mg. to about 390 mg., about 36 mg., about 217 mg., about 386 mg.
  • Unit dosage formulations of the embodiments of the present disclosure can include menthol in the amount of about 1 mg./ml. to about 40 mg./ml, about 10 mg./ml. to about 35 mg./mk, about 20 mg./ml. to about 30 mg./ml., about 23 mg./ml to about 27 mg./ml., about 26 mg./ml to about 30 mg./ml., about 23 mg./ml., about 26 mg./ml, about 30 mg./ml.
  • Unit dosage formulations of the embodiments of the present disclosure can include menthol in the amount per unit of surface area (e.g., surface areas 102 and 104 in FIG.l, in FIG. 2A with surface areas 202 and 204 and in FIG.
  • An effective amount of menthol includes an anesthetic, pain reducing (e.g., analgesic) or anti-inflammatory effective amount of menthol.
  • Menthol may be stabilized using methods know in the art, such as, for example, mixing it with about 0.1 wt% to about 10 wt%, about 0.5 wt% to about 5 wt% of a surfactant including edible nonionic surfactants and ionic surfactants, such as, for example, sucrose fatty acid ester, polysorbate (e.g., polysorbate 80), hydrogenated castor oil (e.g., polyoxyethylene hydrogenated castor oil), cocamidopropyl betaine, etc.
  • a surfactant including edible nonionic surfactants and ionic surfactants, such as, for example, sucrose fatty acid ester, polysorbate (e.g., polysorbate 80), hydrogenated castor oil (e.g., polyoxyethylene hydrogenated castor oil), cocamidopropyl betaine, etc.
  • compositions, methods of making and methods of using included herein which also comprise the menthol component included in embodiments of the present disclosure in a stabilized menthol composition as well as methods of making and using them including a mixture of (a) menthol and (b) a menthol stabilizer compound including undecylenic acid methyl ester or undecylenic acid or a salt (preferably a pharmaceutically acceptable salt) thereof where the menthol in the stabilized menthol compositions is less susceptible to volatizing into a gas and remains in a form that can be administered in a composition in an amount closer to the amount originally included in the composition when formulated with less menthol volatizing away (i.e., lowering the rate of volatilization of the menthol from what it would be for menthol alone) from the original concentration and, thus, lowering the original concentration and diminishing the amount of the menthol originally added.
  • Undecylenic acid salts may include, for example, inorganic acid addition, hydrochloride salts, sulfate and phosphate salts; and organic acid addition salts, such as alkyl sulfonate, arylsulfonate, acetate, maleate, fumarate, tartrate, citrate and lactate and metal salts including alkali metal salts, such as lithium salt, sodium salt and potassium salt and alkaline earth metal salts, such as magnesium salt and calcium salt, strontium salt, aluminum salt and zinc salt, and other multivalent salts such as for example, zirconium, iron, copper, silver, bismuth etc.
  • organic acid addition salts such as alkyl sulfonate, arylsulfonate, acetate, maleate, fumarate, tartrate, citrate and lactate and metal salts including alkali metal salts, such as lithium salt, sodium salt and potassium salt and alkaline earth metal salts, such as magnesium salt and calcium salt, strontium salt
  • the stabilized menthol compositions can made by mixing together (a) menthol and (b) a menthol stabilizer compound in a ratio of (a) about 1 molar part menthol to (b) the amount of one or more than one of the menthol stabilizer compounds (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) of from about 0.005 molar part to about 1.00 molar part, about 0.010 molar part to about 0.750 molar part, about 0.020 molar part to about 0.50 molar part, about 0.050 molar part to about 0.250 molar part, or about 0.10 molar part.
  • menthol stabilizer compounds undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof
  • menthol may associate to form a menthol analog where the menthol analog’ s vapor pressure becomes lower than menthol itself.
  • the menthol component of the menthol analog volatizes as a lower rate than menthol by itself.
  • One possible explanation for the stabilization of menthol by the compound of formula (I) may be that the menthol associates with the alkenyl side chain of the menthol stabilizer compounds (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) may provide a molecular attraction connecting the menthol stabilizer compounds (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) and a menthol molecule, such that more than one menthol molecule may associate with a molecule of one of the menthol stabilizer compounds (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof).
  • the stabilized menthol compositions including menthol and at least one of the menthol stabilizer compounds can be also be made first by dissolving menthol in a pharmaceutically acceptable suitable solvent such as, for example, as a low, medium, or long chain triglyceride.
  • suitable solvent such as, for example, as a low, medium, or long chain triglyceride.
  • suitable solvents are coconut oil, olive oil, palm oil, hemp oil and castor oil.
  • Still other acceptable solvents such as alcohols, ethers and polyalcohols, for example, propylene glycol, butylene glycol, and polyethylene glycols (PEGs) can also be used.
  • the desired amount of at least one of the menthol stabilizer compounds is then added to that mixture.
  • Such compositions that include menthol, solvent and one or more than one of the menthol stabilizer compounds (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) may be made where the mixture of the these ingredients includes a molar ratio of about one molar part menthol to a range of from about 0.0050 molar part to about 1.00 molar part, about 0.010 molar part to about 0.750 molar part, about 0.020 molar part to about 0.50 molar part, about 0.050 molar part to about 0.250 molar part, or about 0.10 molar part of at least one of the menthol stabilizer compounds (undecylenic acid methyl ester, undecy
  • Such mixtures of menthol, solvent and menthol stabilizer compounds may be used when smaller amounts of menthol need to be stabilized (where the amount of menthol stabilizer compound (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) to be mixed with the menthol is so small that there isn’t enough of it to dissolve the menthol).
  • Both menthol stabilized compositions i.e., where the menthol is first dissolved in a solvent then dissolved in a menthol stabilizer compound (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) or where the menthol is directly dissolved in a menthol stabilizer compound (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof)) can be used in orally administrated and non-orally administrated compositions (e.g., non-orally topically administrated compositions (e.g., place on the skin or other external tissues)).
  • non-orally administrated compositions e.g., non-orally topically administrated compositions (e.g., place on the skin or other external tissues)
  • the menthol stabilizer compounds (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) can have a bitter taste.
  • the dissolving of the menthol in solvent prior to the addition of at least one of the menthol stabilizer compounds (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) is preferably used in menthol containing therapeutic compositions to be administered orally because by first dissolving the menthol in a suitable solvent, less of the menthol stabilizer compounds (undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) may be used, thus lessening the bitter taste of the menthol stabilized composition(undecylenic acid methyl ester, undecylenic acid or a salt of undecylenic acid, including mixtures thereof) and the final product in
  • hydrogels for example, a hydrous hydrogel, for the delivery of, for example, pharmaceutical compositions, including analgesic pharmaceutical compositions, that contain a pharmaceutically effective amount of a pharmaceutically acceptable and effective cannabinoid and a pharmaceutically effective amount of menthol and topical compositions, including topical analgesic compositions, that contain a pharmaceutically topical effective amount of a topically acceptable and effective cannabinoid and a pharmaceutically topical effective amount of menthol.
  • pharmaceutical compositions including analgesic pharmaceutical compositions, that contain a pharmaceutically effective amount of a pharmaceutically acceptable and effective cannabinoid and a pharmaceutically effective amount of menthol
  • analgesic pharmaceutical compositions that contain a pharmaceutically effective amount of a pharmaceutically acceptable and effective cannabinoid and a pharmaceutically effective amount of menthol
  • topical analgesic compositions that contain a pharmaceutically topical effective amount of a topically acceptable and effective cannabinoid and a pharmaceutically topical effective amount of menthol.
  • An embodiment of the present disclosure relates to a hydrous hydrogel comprising an aqueous base, a biocompatible polymer, a polyalcohol, a pharmaceutically and/or topically effective amount of a pharmaceutically and topically acceptable and effective cannabinoid, for example, a phytocannabinoid or full spectrum CDB or hemp oil, and a pharmaceutically and/or topically effective amount of a pharmaceutically and topically acceptable and effective menthol.
  • a hydrous hydrogel comprising an aqueous base, a biocompatible polymer, a polyalcohol, a pharmaceutically and/or topically effective amount of a pharmaceutically and topically acceptable and effective cannabinoid, for example, a phytocannabinoid or full spectrum CDB or hemp oil, and a pharmaceutically and/or topically effective amount of a pharmaceutically and topically acceptable and effective menthol.
  • a hydrous hydrogel analgesic composition comprising an aqueous base, a biocompatible polymer, a polyalcohol, a pain reducing (e.g., analgesic and/or anesthetic) and/or anti-inflammatory pharmaceutically and topically effective amount of a pharmaceutically and topically acceptable and effective cannabinoid, for example, a phytocannabinoid or full spectrum CDB or hemp oil, and a pain reducing (e.g., analgesic and/or anesthetic) and/or anti-inflammatory pharmaceutically and topically effective amount of a pharmaceutically and topically acceptable and effective menthol.
  • a pain reducing e.g., analgesic and/or anesthetic
  • a pain reducing e.g., analgesic and/or anesthetic
  • a hydrous hydrogel composition comprising an aqueous base, a pharmaceutically acceptable biocompatible polymer, a pharmaceutically acceptable polyalcohol, a pain reducing (e.g., analgesic and/or anesthetic) and/or anti-inflammatory pharmaceutically and topically effective amount of a pharmaceutically and topically acceptable and effective cannabinoid, for example, a phytocannabinoid, and a pain reducing (e.g., analgesic and/or anesthetic) and/or anti-inflammatory pharmaceutically and topically effective amount of a pharmaceutically and topically acceptable and effective menthol.
  • a pain reducing e.g., analgesic and/or anesthetic
  • a hydrous hydrogel analgesic and/or anti-inflammatory composition comprising an aqueous base, a pharmaceutically and topically pharmaceutically acceptable biocompatible polymer, a pharmaceutically and topically acceptable polyalcohol, a pain reducing (e.g., analgesic and/or anesthetic) and/or anti inflammatory pharmaceutically and topically effective amount of a pharmaceutically and topically acceptable and effective cannabinoid, for example, a phytocannabinoid or full spectrum CDB or hemp oil, and a pain reducing (e.g., analgesic and/or anesthetic) and/or anti-inflammatory pharmaceutically and topically effective amount of a pharmaceutically and topically acceptable and effective menthol.
  • a pain reducing e.g., analgesic and/or anesthetic
  • a pain reducing e.g., analgesic and/or anesthetic
  • the aqueous base can be, for example, water.
  • Water should be deionized and pharmaceutically acceptable free of impurities and microbiological organisms that could harm the user.
  • Total water content (including residual water present in other ingredients) can be in an amount of about 70 wt% to about 95 wt %, about 80 wt% to about 95 wt%, about 82 wt % to about 92 wt%, about 83 wt % to about 91 wt%, about 83 wt%, about 87 wt%, about 91 wt%.
  • Suitable biocompatible polymers that act as gelling, thickening and/or stabilizing agents can include for example of, including pharmaceutically acceptable biocompatible polymers, can include gelatin, agar, sodium carboxymethylcellulose, pectin, sodium alginate, sodium/calcium alginate, polylactic acid, chitosan, carageenan, xanthan, gellan, polyaspartic acid, polyglutamic acid, hyaluronic acid or salts or derivatives thereof.
  • a preferred biocompatible polymer is carageenan.
  • Biocompatible polymer such as, for example, carrageenan, including iota carrageenan, can be in an amount of about 0.5 wt% to about 10 wt %, about 0.5 wt% to about 1 wt%, about 0.75 wt % to about 1 wt%, about 0.75 wt %. Some of the biocompatible polymers may also stabilize the menthol component of embodiments of the present disclosure.
  • Suitable polyalcohols that can act as a humectant to, for example, stabilize oil in water compositions and retain water include pharmaceutically acceptable biocompatible polyalcohols, can include alcohols containing 2 to 10 carbon atoms and 2 to 7 hydroxyl groups including, for example, ethylene glycol, 1,2-propylene glycol, 1,4-butylene glycol, glycerine, glycerine betaine, erythrit (meso-l,2,3,4-Butantetrol), sorbit, mannit, methylglucoside, diglycerine, triglycerine and/or pentaerythrit as well as sodium lactate.
  • alcohols containing 2 to 10 carbon atoms and 2 to 7 hydroxyl groups including, for example, ethylene glycol, 1,2-propylene glycol, 1,4-butylene glycol, glycerine, glycerine betaine, erythrit (meso-l,2,3,4-Butantetrol), sorbit,
  • Polyalcohols such as for example, glycerin can be in an amount of about 1 wt% to about 25 wt %, about 1 wt% to about 4 wt%, about 2 wt % to about 3 wt%, about 3 wt %.
  • An embodiment of the present disclosure relates to a hydrogel composition
  • a hydrogel composition comprising an aqueous base, glycerin, carageenan, a pharmaceutically effective amount of a pharmaceutically and/or topically acceptable and effective cannabinoid, for example, a phytocannabinoid or full spectrum CDB or hemp oil, and a pharmaceutically and/or topically acceptable effective amount of a pharmaceutically acceptable and effective menthol.
  • a hydrogel analgesic composition comprising an aqueous base, glycerin, carageenan, a pain reducing (e.g., analgesic and/or anesthetic) and/or anti-inflammatory pharmaceutically and/or topically effective amount of a pain reducing (e.g., analgesic and/or anesthetic) and/or anti-inflammatory pharmaceutically and/or topically acceptable and effective cannabinoid, for example, a phytocannabinoid, and a pain reducing (e.g., analgesic and/or anesthetic) and/or anti-inflammatory pharmaceutically and /or topically effective amount of a pain reducing (e.g., analgesic and/or anesthetic and/or anesthetic) and/or anti-inflammatory pharmaceutically and/or topically acceptable and effective menthol.
  • a pain reducing e.g., analgesic and/or anesthetic
  • the hydrogel comprises an aqueous base (including water) in an amount of 70 wt% to about 95 wt %, about 80 wt% to about 95 wt%, about 82 wt % to about 92 wt%, about 83 wt % to about 91 wt%, about 83 wt%, about 87 wt%, about 91 wt%, the biocompatible polymer (including carageenan) in an amount of about 0.5 wt% to about 5 wt %, about 0.5 wt% to about 1 wt%, about 0.75 wt % to about 1 wt%, about 0.75 wt %, the poly alcohol (including glycerine) in an amount of about 1 wt% to about 5 wt %, about 1 wt% to about 4 wt%, about 2 wt % to about 3 wt%, about 3 wtt%, about 3 wt
  • menthol in an amount of about 1 wt% to about 10 wt %, about 5 wt% to about 10 wt%, about 5 wt %, about 6 wt%, about 8 wt% including unit dosage amounts of 2 mg. to about 400 mg., about 30 mg. to about 40 mg., about 210 mg. to about 220 mg., about 380 mg. to about 390 mg., about 36 mg., about 217 mg., about 386 mg, about 1 mg./ml. to about 40 mg./ml, about 10 mg./ml. to about 35 mg./ml., about 20 mg./ml.
  • the hydrogel comprises water in an amount of 70 wt% to about 95 wt %, about 80 wt% to about 95 wt%, about 82 wt % to about 92 wt%, about 83 wt % to about 91 wt%, about 83 wt%, about 87 wt%, about 91 wt%, carageenan in an amount of about 0.5 wt% to about 5 wt %, about 0.5 wt% to about 1 wt%, about 0.75 wt % to about 1 wt%, about 0.75 wt %; glycerin in an amount of about 1 wt% to about 5 wt %, about 1 wt% to about 4 wt%, about 2 wt % to about 3 wt%, about 3 wt %; cannabinoid, for example, phytocannabinoids and full spectrum CBD or hemp oil, in
  • Full spectrum hemp oil can be in an amount of 0.1 wt% to about 10 wt%, about 0.5 wt% to about 5 wt%, about 0.5 wt% to about 2 wt% %, about 2 wt%, about 2.1 wt%, about 4 wt% including unit dosage amounts of about 2 mg. to about 195 mg., about 14 mg. to about 100 mg., about 14 mg. to about 80 mg., about 70 mg. to about 195 mg., about 10 mg. to about 15 mg, about 70 mg. to about 80 mg, about 1900 mg. to about 195 mg, about 14 mg, about 77 mg, about 193 mg, about 5 mg./ml. to about 40 mg./ml., about 5 mg./ml.
  • menthol in an amount of about 1 wt% to about 10 wt %, about 5 wt% to about 10 wt%, about 5 wt %, about 6 wt%, about 8 wt% including unit dosage amounts of 2 mg. to about 400 mg., about 30 mg. to about 40 mg., about 210 mg. to about 220 mg., about 380 mg. to about 390 mg., about 36 mg., about 217 mg., about 386 mg, about 1 mg./ml. to about 40 mg./ml, about 10 mg./ml.
  • treating and “effective amount”, as used herein, unless otherwise indicated, means reversing, alleviating, inhibiting the progress of, or preventing the disorder or condition to which such term applies, or one or more symptoms of such disorder or condition.
  • treatment refers to the act of treating as “treating” is defined immediately above.
  • treating also includes adjuvant and neo-adjuvant treatment of a subject.
  • kits are disclosed.
  • a kit including a composition or unit dose composition (e.g., a patch or mass of embodiment composition) of one of the embodiments of the present disclosure including multiple unit doses and instructions for use.
  • Optional ingredients include skin oil cleanser and/or cooling agents such as, for example, denatured alcohol or isopropyl alcohol.
  • Skin oil cleanser and/or cooling agents can include, for example, alcohols such as denatured alcohol or isopropyl alcohol.
  • alcohols such as denatured alcohol or isopropyl alcohol.
  • One purpose of such a skin oil cleanser and/or cooling agents would be to break up oil deposits on the skin where the composition is applied where such deposits may interfere with the transdermal passage of the cannabinoid and menthol ingredients into the tissue beneath the skin layer.
  • Skin oil cleanser and/or cooling agents such as, for example, denatured alcohol can be generally used at levels of from about 0.1 wt% to about 2 wt%, about 0.5 wt% to about 1.5 wt%, about 1 wt% to about 2 wt%, about 1 wt%.
  • the hydrogel comprises an aqueous base (including water) in an amount of 70 wt% to about 95 wt %, about 80 wt% to about 95 wt%, about 82 wt % to about 92 wt%, about 83 wt % to about 91 wt%, about 83 wt%, about 87 wt%, about 91 wt%, the biocompatible polymer (including carageenan) in an amount of about 0.5 wt% to about 5 wt %, about 0.5 wt% to about 1 wt%, about 0.75 wt % to about 1 wt%, about 0.75 wt %, the poly alcohol (including glycerine) in an amount of about 1 wt% to about 5 wt %, about 1 wt% to about 4 wt%, about 2 wt % to about 3 wt%, about 3 wtt%, about 3 wt
  • CBD can be in an amount of 0.1 wt% to about 10 wt%, about 0.5 wt% to about 5 wt%, about 0.5 wt% to about 2 wt% %, about 2 wt%, about 2.1 wt%, about 4 wt% including unit dosage amounts of about 2 mg. to about 195 mg., about 14 mg. to about 100 mg., about 14 mg. to about 80 mg., about 70 mg. to about 195 mg., about 10 mg. to about 15 mg, about 70 mg. to about 80 mg, about 1900 mg. to about 195 mg, about 14 mg, about 77 mg, about 193 mg, about 5 mg./ml. to about 40 mg./ml., about 5 mg./ml.
  • menthol in an amount of about 1 wt% to about 10 wt %, about 5 wt% to about 10 wt%, about 5 wt %, about 6 wt%, about 8 wt% including unit dosage amounts of 2 mg. to about 400 mg., about 30 mg. to about 40 mg., about 210 mg. to about 220 mg., about 380 mg. to about 390 mg., about 36 mg., about 217 mg., about 386 mg, about 1 mg./ml. to about 40 mg./ml, about 10 mg./ml.
  • a skin oil cleanser and/or cooling agent including denatured alcohol in an amount of about 0.1 wt% to about 2 wt%, about 1 wt% to about 2 wt%, about 1 wt%.
  • the hydrogel comprises about 3.0 wt% glycerin; about 91 wt% water; about 1.0 wt% denatured alcohol; about 5 wt% menthol (about 36.33 mg; about 23 mg./ml.); and about 2.0 wt% full spectrum CBD or hemp oil (about 14.53 mg; about 9.2 mg./ml.).
  • the hydrogel comprises about 3.0 wt% glycerin; about 87 wt% water; about 1.0 wt% denatured alcohol; about 6 wt% menthol (about 217 mg; about 26 mg./ml); and about 2.0 wt% full spectrum CBD or hemp oil (about 77 mg; about 9.4 mg./ml.).
  • the hydrogel comprises about 3.0 wt% glycerin; about 83 wt% water; about 1.0 wt% denatured alcohol; about 8 wt% menthol (about 386 mg; about 30 mg./ml.); and about 4.0 wt% full spectrum CBD or hemp oil (about 193 mg; about 15 mg./ml.).
  • Embodiments of the present disclosure may be delivered for local or systemic administration to a body part of a person to be treated with the embodiment, for example, a body or skin surface by placing an embodiment of the present disclosure on a body part or skin surface thereof in active agent-transmitting relation thereto, the active agents being cannabinoid, for example, phytocannabinoid or full spectrum CDB or hemp oil, and menthol.
  • an embodiment of the present disclosure may be incorporated into a delivery system, such as a unit dose delivery system (e.g. a "patch.”).
  • the hydrogel adhesive composition may be cast or extruded onto a backing layer or release liner and the surface from which the backing layer or release liner was removed can serve as the skin-contacting face of the system and act as an active agent reservoir.
  • the hydrogel composition may be used as an active agent reservoir within the interior of such a system, with a conventional skin or other body part contact adhesive laminated thereto to affix the system to a body part or skin surface thereof.
  • the cannabinoid for example, CBD or full spectrum CDB or hemp oil, could be in the reservoir and the menthol in the hydrogel housing the reservoir.
  • Other embodiments of the present disclosure include a method of relieving pain and /or inflammation by topically administering and placed topically to a body part (e.g., arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them), of a mammal (e.g., a human patient or veterinary patient) in need of such treatment at least one of the compositions disclosed herein.
  • a body part e.g., arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them
  • a mammal e.g., a human patient or veterinary patient
  • Still other embodiments of the present disclosure include a method of relieving bodily pain (local and/or systemic) by topically administering to placed topically on a body part (e.g., arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them), of a mammal (e.g., a human patient or veterinary patient) in need of such treatment at least one of the compositions disclosed herein.
  • a body part e.g., arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them
  • a mammal e.g., a human patient or veterinary patient
  • Still other embodiments of the present disclosure include a method of relieving pain and /or inflammation (local and/or systemic) by administering to a body part, for example, placed topically on an arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them, of a mammal (e.g., a human patient or veterinary patient) in need of such treatment at least one of the compositions disclosed herein.
  • a mammal e.g., a human patient or veterinary patient
  • Still other embodiments of the present disclosure include a method of relieving bodily pain and /or inflammation (local and/or systemic) by topically administering to placed topically on a body part (e.g., arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them), of a mammal (e.g., a human patient or veterinary patient) in need of such treatment at least one of the compositions disclosed herein by placing the composition topically on a body part (e.g., arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them).
  • a body part e.g., arm, leg, knee, torso, head, neck, foot as well as those parts that make-up them.
  • the dosing time can range from about 30 minutes to about 12 hours, about 30 minutes to about 8 hours (based on in vitro testing), 30 minutes to about 2 hours or about 30 minutes to about 1 hour.
  • Another embodiment of the present disclosure relates to a composition containing particles which have a core containing an active agent or a salt thereof coated with a barrier layer.
  • the barrier layer is formed from a coating liquid that contains a least one water insoluble barrier forming component selected from a group consisting of ethyl cellulose, copolymers of acrylic and methacrylic esters and natural or synthetic waxes, and a plasticizer.
  • the amount of the active agent administered may be dependent on the subject being treated, the severity of the disorder or condition, the rate of administration, the disposition of the compound and the discretion of the prescribing physician.
  • an effective dosage is in the range of about 0.001 to about 100 mg. per kg body weight per day, preferably about 1 to about 35 mg./kg/day, in single or divided doses. For a 70 kg human, this would amount to about 0.05 to about 7 g/day, preferably about 0.1 to about 2.5 g/day.
  • dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases still larger doses may be employed without causing any harmful side effect, provided that such larger doses are first divided into several small doses for administration throughout the day.
  • any standard manufacturing procedure known in the art may be used to manufacture the hydrous hydrogels of the present disclosure.
  • a vessel with or without mixing
  • the biocompatible polymer e.g., carrageenan
  • the polyalcohol e.g., glycerin
  • a surfactant e.g., polysorbate 80
  • the mixture from the vessel is cast or spread into a hydrogel film and passed through at refrigerated tunnel at about 30° C to about 50° C or colder. The colder the refrigerated tunnel, the less water that is evaporated or lost from the hydrogel film.
  • the hydrogel film can then be cut or divided into various forms and sizes e.g., the embodiments of the present disclosure. After it is cut or divided, the hydrogel can be placed in its packaging and sprayed with the skin oil cleanser and/or cooling agent (e.g., denatured alcohol or isopropyl alcohol) to coat its exterior surface including surface areas shown in the figures of the present disclosure, immediately before sealing the package, for example, the package embodiment of the present disclosure.
  • the skin oil cleanser and/or cooling agent e.g., denatured alcohol or isopropyl alcohol
  • inventions of the present disclosure can be extruded directly onto a substrate such as a backing layer or release liner, and then pressed.
  • Systems for the topical or transdermal administration of an active agent may comprise: a reservoir containing a therapeutically effective amount of an active agent; an adhesive means for maintaining the system in active agent transmitting relationship to a body surface; and a backing layer as described above, wherein a disposable release liner covers the otherwise exposed surface, protecting such surface during storage and prior to such surface being applied topically (also as described above).
  • compositions, patch or device of the present disclosure will contain a quantity of an active agent effective to provide the desired dosage or effect over a predetermined delivery period.
  • the compositions, patch or device of the present disclosure include the hydrogel compositions as well as masses thereof including patches and other shapes that can be topically applied topically to a body part or portion thereof
  • compositions of the present disclosure may also include a rate-controlling membrane on the body surface side of the drug reservoir.
  • the materials used to form such a membrane are selected to limit the flux of one or more components contained in the drug formulation, and the membrane may be either microporous or dense.
  • Representative materials useful for forming rate-controlling membranes include polyolefins such as polyethylene and polypropylene, polyamides, polyesters, ethylene-ethacrylate copolymer, ethylene-vinyl acetate copolymer, ethylene-vinyl methylacetate copolymer, ethylene-vinyl ethylacetate copolymer, ethylene-vinyl propylacetate copolymer, polyisoprene, polyacrylonitrile, ethylene -propylene copolymer, polysiloxane-polycarbonate block copolymer and the like.
  • An example of such a kit is a sealed water-proof package containing an embodiment of the present disclosure.
  • FIGS. 4A and 4B Another aspect of the present disclosure is a water-proof package designed to contain of the composition or patch embodiments of the present disclosure and to keep a substantial amount of the moisture (i.e., water) in the embodiment.
  • One package embodiment is illustrated in FIGS. 4A and 4B and can include foil enclosure 400 with side sections 402 and 404 that are sealed together along a common peripheral edge 406. Inside the enclosure 400 is an internal void in which a patch 408 is positioned.
  • Size of unit dose patch 6.5 cm x 4.2 cm (27.3 cm 2 ) with thickness from .0508 cm to .06604 cm. volume about 1.58 ml, total weight 762.62 mg.
  • Size of unit dose patch 10 cm x 14 cm (140 cm 2 ) with thickness from .0508 cm to .06604 cm. volume about 8.176 ml, total weight 3633 mg.
  • Size of unit dose patch 12 cm x 16 cm (192 cm 2 ) with thickness from .0508 cm to .06604 cm. volume about 12.68 ml, total weight 4830 mg.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne des compositions ainsi que des procédés d'utilisation et des procédés de fabrication, des compositions d'hydrogel hydraté utiles en tant qu'analgésiques oraux topiques comprenant des cannabinoïdes et du menthol, le composant menthol pouvant être une composition de menthol stabilisée comprenant du menthol et au moins un composé stabilisateur de menthol comprenant un ester méthylique d'acide undécylénique, un acide undécylénique ou un sel d'acide undécylénique.
PCT/US2020/020722 2020-03-03 2020-03-03 Compositions à base de gel de menthol et de cannabinoïdes, timbres et procédés WO2021177940A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US2020/020722 WO2021177940A1 (fr) 2020-03-03 2020-03-03 Compositions à base de gel de menthol et de cannabinoïdes, timbres et procédés

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2020/020722 WO2021177940A1 (fr) 2020-03-03 2020-03-03 Compositions à base de gel de menthol et de cannabinoïdes, timbres et procédés

Publications (1)

Publication Number Publication Date
WO2021177940A1 true WO2021177940A1 (fr) 2021-09-10

Family

ID=77613674

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2020/020722 WO2021177940A1 (fr) 2020-03-03 2020-03-03 Compositions à base de gel de menthol et de cannabinoïdes, timbres et procédés

Country Status (1)

Country Link
WO (1) WO2021177940A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022159507A1 (fr) * 2021-01-19 2022-07-28 Merit Therapeutics, Inc. Combinaison de cannabinoïdes avec des agents thérapeutiques supplémentaires pour le traitement de maladies ou de troubles

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5869087A (en) * 1994-09-16 1999-02-09 Hisamitsu Pharmaceutical Co., Inc. Patch having a preparation for external use attached thereto
US20170020942A1 (en) * 2015-07-24 2017-01-26 Shabana Naheed Medication dispensing system
US20190110981A1 (en) * 2017-10-17 2019-04-18 Life Tech Global, Llc Cannabinoid Patch

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5869087A (en) * 1994-09-16 1999-02-09 Hisamitsu Pharmaceutical Co., Inc. Patch having a preparation for external use attached thereto
US20170020942A1 (en) * 2015-07-24 2017-01-26 Shabana Naheed Medication dispensing system
US20190110981A1 (en) * 2017-10-17 2019-04-18 Life Tech Global, Llc Cannabinoid Patch

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "Carrageenan - Wikipedia, the free encyclopedia", 16 May 2020 (2020-05-16), pages 1 - 8, XP055855931, Retrieved from the Internet <URL:https://en.wikipedia.org/w/index.php?title=Carrageenan&oldid=957027398> [retrieved on 20211028] *
ANONYMOUS: "Menthol - Wikipedia, the free encyclopedia", 28 April 2020 (2020-04-28), pages 1 - 12, XP055855934, Retrieved from the Internet <URL:https://en.wikipedia.org/w/index.php?title=Menthol&oldid=953714056> [retrieved on 20211028] *
PRAKASH NAGARKATTI, RUPAL PANDEY, SADIYE AMCAOGLU RIEDER, VENKATESH L HEGDE, MITZI NAGARKATTI: "Cannabinoids as novel anti-inflammatory drugs", FUTURE MEDICINAL CHEMISTRY, FUTURE SCIENCE LTD., GB, vol. 1, no. 7, 1 October 2009 (2009-10-01), GB , pages 1333 - 1349, XP055533169, ISSN: 1756-8919, DOI: 10.4155/fmc.09.93 *
REVERE HEALTH: "Systemic Diseases Versus Localized Diseases ", LIVE BETTER, 29 August 2016 (2016-08-29), pages 1 - 9, XP055855937, Retrieved from the Internet <URL:https://reverehealth.com/live-better/systemic-diseases-versus-localized-diseases/> [retrieved on 20211028] *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022159507A1 (fr) * 2021-01-19 2022-07-28 Merit Therapeutics, Inc. Combinaison de cannabinoïdes avec des agents thérapeutiques supplémentaires pour le traitement de maladies ou de troubles

Similar Documents

Publication Publication Date Title
WO2020051117A1 (fr) Compositions de gel au menthol et aux cannabinoïdes, patchs et méthodes
RU2467759C2 (ru) Состав для местного использования и его применения
JP6591536B2 (ja) 特定の投薬量の活性物質を皮膚又は粘膜に投与するための電気流体力学的に得られた繊維を含む組成物
SK12962002A3 (sk) Použitie farmaceuticky prijateľného topického prostriedku, náplasť, prostriedok a nádoba
US20240082175A1 (en) Cannabinoid and menthol transdermal delivery systems and methods
EP3735225A1 (fr) Compositions topiques soulageant la douleur
JP2010531298A (ja) 疼痛を治療するための局所用組成物
US20210000759A1 (en) Cannabinoid and menthol compositions and methods
KR102251124B1 (ko) 수계 캡사이시노이드 제형 및 제조방법 및 용도
KR100946605B1 (ko) 소염 진통 첩부제
US11147775B2 (en) Cannabinoid and menthol gel compositions, patches and methods
US11229610B2 (en) Cannabinoid and menthol gel compositions, patches and methods
WO2021177940A1 (fr) Compositions à base de gel de menthol et de cannabinoïdes, timbres et procédés
JP6628488B2 (ja) ゲル状外用組成物
CN101496833B (zh) 马钱子总生物碱制备的液体外用制剂
ES2394313T3 (es) Formulación transdérmica que comprende un analgésico opioide y una composición de aloe
WO2004110468A1 (fr) Compositions transdermiques et procedes de traitement afin de soulager ou de prevenir les migraines et les symptomes associes
CN117460500A (zh) 止痛贴片
US20210000899A1 (en) Veterinary cannabinoid and menthol compositions and methods
JPH10513454A (ja) ルビジウムイオンを用いる治療法およびその製剤
US20160101141A1 (en) Topical Treatment of Sports Related Injuries
US20220062603A1 (en) Cannabinoid and menthol transdermal delivery systems and methods
US11344495B2 (en) Veterinary cannabinoid, menthol and anesthetic compositions and methods
KR20170113913A (ko) 메칠설포닐메탄 및 글루코사민이 포집된 나노리포좀을 포함하는 국소도포 제제 조성물
WO2021177937A1 (fr) Compositions à base de cannabinoïdes et de menthol et procédés associés

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20923430

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 20923430

Country of ref document: EP

Kind code of ref document: A1