TWI222882B - Pharmaceutical formulations - Google Patents

Abstract

The invention relates to pharmaceutical formulations for use in the administration of lipophilic medicaments via mucosal surfaces. In particular the invention provides pharmaceutical formulations for use in administration of a lipophilic medicament via a mucosal surface which upon hydration form an emulsion containing the lipophilic medicament which is capable of adhering to a mucosal surface and allowing controlled release of the medicament. The invention further provides pharmaceutical formulations which contain, as active ingredients, specific combinations of cannabinoids in pre-defined ratios.

Description

1222882

The present invention relates to a pharmaceutical formulation for administering a drug, particularly a lipophilic drug, through a mucosal surface. Oral swallowing drugs are first absorbed into blood that perfuses the gastrointestinal tract. The venous drainage area from the gastrointestinal tract is the blood that enters the perfused liver. This means that the drugs absorbed through the lumen of the gastrointestinal tract are immediately delivered to the liver and to the body's main detoxification organ. In addition to protecting the organism from ingestion of toxins, the liver also metabolizes drugs and treats them in the same way. The blood from the liver then returns to the left side of the heart through the hepatic portal vein and reaches the rest of the systemic circulation. Passing through the liver in this way first may result in a considerable portion of the medication being removed. The effects of the first pass are more pronounced in some drugs than others; in the case of cannabinoids, more than 90% of the food is taken. The amount is removed on the first pass. Some areas of the nutritional pipeline have venous drainage basins that do not involve the first pass through the liver. These areas (oral mucosa, sublingual and nasopharynx, and distal rectum) flow directly into the left heart. Avoiding first-pass effects is the reason for buccal, nasal, and sublingual dosage forms, and suppositories. Each of these formulations has advantages and disadvantages as follows. Suppositories are limited by hygiene and patient compliance. Formulas administered to the nasal mucosa can easily cause pain and reflex sneezing. In extreme cases, they may cause irritation and damage to the nasal mucosa. Sublingual formulations may stimulate saliva outflow, and patients will inevitably swallow when too much saliva is produced. The buccal formula has the same limitations. Both sublingual and buccal formulations are related to the effective transfer of the drug from a hydrophilic vehicle to the sublingual or buccal mucosa. The transfer of drugs through the epithelium is mainly controlled by the lipid solubility of the drugs. When the drug is water-insoluble, there is another 4 (please read the precautions on the back before filling this page). Order — This paper size is applicable to China National Standard (CNS) A4 specification (210X297 public luxury) 1222882 A7 ____ B7 _ V. Invention Explanation (2) Prevents its absorption from the sublingual area. Therefore, oral and swallowing of lipophilic drugs such as cannabis and cannabinoids have physical and biological limitations for their therapeutic use. The present invention relates to formulations that are particularly suitable for administering lipophilic drugs through mucous membranes, such as the sublingual or buccal mucosa. Therefore, according to a first characteristic aspect of the present invention, there is provided a pharmaceutical formula for administering a lipophilic drug via a mucosal surface, comprising at least one lipophilic drug and at least one self-emulsifying agent, wherein the formula forms Lipid drug emulsion that adheres to the surface of the mucosa and allows controlled release of the drug. Direct experiments have shown that when lipophilic drugs are formulated as self-emulsifying formulations, lipophilic drugs can be effectively in intimate contact with the absorbing mucosa. In the context of the present invention, it should be understood that the following terms are defined as follows. A "self-emulsifier" is a chemical that can form an emulsion when another phase is present with minimal energy requirements. In contrast, emulsifiers, in contrast to self-emulsifiers, require additional energy to form an emulsion. The spray formulation disclosed here, self-emulsifying occurs when it comes into contact with another phase (saliva). A "primary" (self) emulsifier is used as a (self) emulsifier for its main function. Secondary (self) emulsifiers are used as (self) emulsifiers for their secondary functional systems. Another function of a secondary (self) emulsifier is, for example, as a solubilizer or tackifier. Briefly, § self-emulsifiers are soluble soaps, salts or sulfated alcohols, especially non-ionic surfactants or fourth compounds. These compounds are commonly referred to as self-emulsifying grades (SE grades) such as SE grade glyceryl monooleate and glutamate grade — * This paper is compliant with the Financial Standards (CNS) A4 specification ^^ 297 mm) ----- — »Dance" (Please read the notes on the back before filling this page),-= 口. ^ 22882 A7 —_____ B7_____ V. Description of the invention (3) Oil-based monostearate. The "hydrophilic-lipophilic balance" (HLB) system and the balance between the hydrophilic and lipophilic portions of the surface-active molecules, HLB is used as the basis for a reasonable means of selecting and classifying emulsifiers. In the HLB system, each emulsifier is assigned a number of j to 20 (refer to Pharmacopoeia). Emulsifiers with HLB values of 3 to 6 are lipophilic ' to form water-in-oil emulsions, and HLB values of 8 to 18 indicate the main hydrophilic properties to form oil-in-water emulsions. Emulsifiers preferred for use in the present invention typically have an HLB value of 8 to 180. Unexpectedly, the formulations according to the present invention do not cause reflective secretion of saliva because the secreted saliva is attracted into the dosage unit in situ An emulsified substance is formed. Further, the substance thus formed adheres to the surface of the mucosa and forms a layer on the surface of the mucosa, typically the buccal mucosa and / or the sublingual mucosa, thereby providing a controlled release formulation. In a preferred embodiment, the formulation of the present invention is not a propellant-driven aerosol or liquid spray. The formulation of liquid formulations of oropharyngeal cannabinoids poses a number of problems. First, at least 10 milligrams, preferably at least 2.5 milligrams, and still more preferably at least 5 milligrams of cannabinoids are delivered per 0.1 milliliter of liquid formula to achieve a therapeutic effect. In this regard, a patient may require up to about 20 mg / day of cannabinoids on average about 40 mg / day, with a maximum of 6 doses per day. In the case of sublingual or buccal delivery, this means that if the active ingredient is to be absorbed through the mucosa, the amount of active ingredient in this formulation cannot be swallowed by the patient. Although such a dose can be achieved by dissolving cannabinoids in ethanol as a solvent, the concentration of ethanol in the rain caused a tingling sensation that has exceeded this paper standard and applies Chinese National Standard (CNS) A4 specifications (210X297) ··)

One swallow. (Please read the precautions on the back before filling in this page.) 5. Description of the invention (4) Out of tolerance. The amount 'while still so requires the use of a co-solvent to reduce the use of ethanol to maintain a sufficient amount of cannabinoid-soluble. The applicant finds that the choice of cosolvent is limited, and must choose ... 1) can be used as a solubility enhancer, or π) has a solubilizing effect, which is sufficient to allow a sufficient amount of cannabis to be secreted in a single amount = that is at least K0 mg / (U ml formula, which allows the presence of the solvent to reduce the extent to which the patient can tolerate the co-solvent. According to the above item i), especially when the co-solvent is a polyoxyethylene castor oil derivative 'especially grammar Buddha (Cremopaph). As regards the aforementioned particularly suitable co-solvents for item ii) are propylene glycol and glycerol. Preferably, the formulation of the present invention is a solid dosage form such as a solid gel (e.g., a gel having elasticity but having dimensional stability), a support agent, a compressed lozenge, a lozenge, a gelatin capsule, etc., or a gel spray. The units in the agent are preferably uniform in composition, and within the scope of the present invention also include multi-layered dosage units formed of multiple layers with different compositions, such as double-layer tablets and double-layer gels, as shown in the drawings, where different layers contain different active ingredients and / Or have different release characteristics. The gel spray formulation also includes one or more solvents and optionally one or more co-solvents. Suitable solvents for gel spray formulations include ethanol. Suitable co-solvents include glycerol. Gel spray formulations can be distinguished from "liquid" formulations based on viscosity. Gel sprays are usually thicker than pure ethanol solutions. Typically, the viscosity of a gel spray is in the range of 100,000 to 20,000 centipoise. V. Description of the invention (5) Suitable self-emulsifiers that can be included in the formulations of the present invention include those suitable for use in Table 2 as the primary and secondary emulsifiers. Preferred self-emulsifying agents include glyceryl monooleate and glyceryl monostearate (particularly self-emulsifying grades). Glycerol monooleate and glyceryl monostearate (non-self-emulsifying grade) are usually used, for example, adding a small amount of alkali 俾 to produce a "self-emulsifying" agent. Used in solid dosage formulations. The total amount of self-emulsifier in the formulation is preferably at least 5% w / w and more preferably at least 10% w / w. For gel spray formulations, the total amount of self-emulsifiers included in the formulation is preferably at least 2% w / w and more preferably at least 5% w / w. The total amount of self-emulsifiers is usually proportional to the total amount of active ingredients (lipophilic drugs) contained in the formula; the higher the active ingredient content, the greater the content of self-emulsifiers. The formulations according to the invention are intended to contain an active ingredient content above 1%. Preferably, the relative ratio of the self-saccharifying agent to the active ingredient is between 10% of the active ingredient and a self-emulsifier to 1% of the 5% active ingredient. The total amount of self-emulsifiers can also change the predetermined dissolution / disintegration characteristics in the mouth. The reason is that increasing the content of self-emulsifiers has the effect of extending the dissolution / disintegration time (see Example 14). ▲ The formula further contains-or multiple tackifiers (chemical agents to increase viscosity). Suitable tackifiers include the tackifiers listed in Table 2 below. A preferred tackifier is a drum segment copolymer of oxyethylene and oxypropylene. Better tackifiers are non-ionic surfactants. In the examples described below, the formula contains ㈣ = i, which is a non-ionic surfactant, but additionally contains at least one tackifier, which is not a non-ionic surfactant. In a preferred embodiment, the formulation contains at least one tincture, and the invention description can be dissolved by the action of the enzyme present in the saliva towel. Examples of such thickeners include pre-gelatinized starch, which is soluble by the action of sialylase, and is a thickener that is only sensitive to enzymatic knifebreaking. Substance 'This substance has the best absorption from the oral cavity and sublingual mucosa. This has the advantage of allowing solid gels to dissolve quickly (for example within a few minutes.) A wide variety of lipophilic tackifiers are used in pharmaceutical formulations. Gels formed by the hydration of these substances are known to have surface charges. Table 2 lists several chemical agents (But not limited to the scope of the present invention), which has such properties, indicating that it is approved by law for preparations intended for oral administration. The table also indicates the known surface charge symbol. In a preferred embodiment, the formulation contains at least A tackifier that forms a gel when hydrated and has a positive surface charge, and at least one tackifier that forms a gel with a negative surface charge when hydrated. In a preferred embodiment, the formulation includes At least one tackifier that forms a gel with a positive surface charge when hydrated, which is gelatin or sugar gelatin; and at least one tackifier that forms a gel with a negative surface charge when hydrated, which is starch, Gelatinization; powder, acacia or polydextrose. Unexpectedly, by selecting a mixture of materials that can produce gels with opposite charges, the resulting mixture can be modified. The solubility characteristics control the rate of drug release from this formula, especially the dissolution of at least one of the components by the amylolytic enzymes present in saliva. It can be changed by changing the total amount of thickener, and also by forming positive and negative surfaces. China National Standard (CNS) A4 (210X297 mm)

f Thai noodles (please read the precautions on the back before filling this page), π—0 !, modify the physical properties of the dosage form with 2882 V, invention description (7) charge gel material ratio. Usually increasing the relative amount of positively charged tackifiers (such as gelatin or sugar gelatin) has a slowing effect on dissolution / disintegration in the mouth, while increasing the relative amount of negatively charged tackifiers (such as starch or pregelatinized starch) has an acceleration in the mouth Dissolution / disintegration effect (refer to Figure 14). The proportion of the positive and negatively charged tackifiers in the formulation can be changed to form a dosage form with the required release characteristics. For solid dosage forms, the total amount of tackifier (including any gelling agent) in the formula is better than 60% w / w of the formula. For gel spray formulations, the total amount of tackifier included in the formula is preferably 1% w / w of the formula, and more preferably 2% w / w of the formula. Preferred tackifiers for inclusion in breaker spray formulations include, for example, carboxymethyl cellulose. Other excipients may be included in the formulations of the present invention as needed. For example, the formulation may contain one or more antioxidants. Preferred antioxidants include cardiotocopheryl ascorbyl palmitate, butylated hydroxyanisole (BHA), and the like. Formulations also include one or more colorants. Suitable colorants include, for example, very flavin or chlorophyll. The accompanying example illustrates the most ideal formula for obtaining strong lipophilic drugs to be absorbed through the mucosa and sublingual epithelium. This formula can obtain the pharmacodynamic profile of the most desired therapeutic effect. The formula contains at least one self-emulsifying component, which is a filiform emulsion during reading, which reversibly adheres to the membrane without causing irritation or damage, or stimulating excessive secretion of saliva. When the form is introduced into the lower or upper popliteal fossa or placed under the tongue, the dosage form hydrolyzes to the mucous membranes. The hydrolyzed emulsified substance thus formed maintains contact with a large area of the mucosa and the sublingual mucosa, and releases the drug over a period of time. Cheek Adhesive Adhesive Cheeks

， 可 | (Please read the precautions on the back before filling this page) 1222882 V. Description of the invention (Controlled release characteristics of the formula can also be changed by changing the relative content of the excipients contained in the formula, especially since the viscosity needs to be increased The content of the agent is changed / < Ding Lihua agent and-Duanzuo Li L is the teaching materials _ surface experience㈣ :, all lipophilic drugs are absorbed through the mucosal surface into the time. The absorption rate of lipophilic drugs is obviously based on Medicinal bettapine. Taking cannabinoids as an example, significant absorption through the mucous membrane of the tongue or sublingual can be achieved in about 10 minutes. Therefore, any formula that hopes to deliver cannabis-like drugs can be maintained: on the shellfish, contact with the mucosal surface at least After this period of time. The best formula of the present invention will completely disintegrate within 0160 minutes, preferably 0.5-5 minutes, but the formula of the present invention is manufactured so that the disintegration time is at least 90 minutes. Table 2 lists when the dosage unit is placed in contact Included pharmaceutically acceptable excipients and types of excipients (but not limited to the present invention) for saliva to obtain an appropriate viscosity. The dosage form can be sealed in a mold that can be shielded from light and air Manufactured by melting or compression. According to a second characteristic aspect of the present invention, a pharmaceutical formulation for administering a lipophilic drug through a mucosal surface is provided, the formulation comprising at least one lipophilic drug, at least one solvent, at least one co-solvent, Jia is also a solubilizer, and at least one self-emulsifier. When hydrated, the formulation forms an emulsion containing lipophilic drugs that can adhere to the surface of the mucosa and allow controlled release of the drug. It is characterized by the solvent and the The total amount of solvent is greater than 55% w / w of the formula. Preferably, in the embodiment, the formula may be a liquid dosage form such as an aerosol, a liquid spray or a drop. The self-emulsifying formula is adhered to the mucous membrane to undergo the paper Standards apply to China National Standard (CNS) A4 specifications (210X297 public transformer)

...... | (Please read the precautions on the back — II> • Order 丨 1222882 V. Description of the invention (9) I is enough for the lipophilic drug to absorb time and deliver The technical principle of lipophilic active ingredients to the surface of the mucosa can be extended to liquid dosage forms. The preferred embodiment is a liquid formulation administered via a pumping spray. The pumping spray is particularly useful when transporting cannabinoids. It is true that the first month 〔People consider pumping sprays not suitable for drug delivery, and focus on propellant-containing solvent systems. Although understanding the disadvantages of such systems, including the disadvantages of delivery speed, it has been hot for artists to try to change the nozzle Slowing the propellant to solve this problem. The applicant has found that the use of a pumped spray formulation can produce a spray in which the particles have an average aerodynamic particle size of 15 to 45 microns, in particular 20 to 40 millimeters and an average of about 33 microns. This is the opposite of particles with an average aerodynamic particle size of 5 to 10 microns when delivered using a pressurized system. In fact, comparative tests performed by the applicant show pumping effect spray systems The advantage is that the active ingredient can be delivered to a larger surface area in the target area. An example will be described with reference to the attached example 12. The particle distribution and the change in spray area are verified through direct experiments. The formula is packed in pumping as described in example 12 Action spray assembly (inspired by Valois vial VP7 i 00). The same formula can be filled in a pressurized container powered by Yeba 134a. The two containers are placed at a distance of 50mm from a sheet of thin paper. Discharge, the tissue paper is at a right angle with respect to the travelling direction of the jet. Then, in two cases, the spray pattern generated by microliters was observed visually. The discharge patterns in both cases were circular, and the measured values are as follows: Average area ( Square millimeters) This paper is sized for China National Standard (CNS) A4 (210X297 mm)

• Order · 0! (Please read the precautions on the back before filling out this page) 1222882 Five Descriptions of the Invention 10 Pumping Action Spray --- ~~~~~ -_ Pressure Spray 23 16 Pressurization will cause the liquid to condense in the Area. 、,. ^. ^ The chestnut effect spray season is a uniform collection style and less "rebound". The suitable action spray covers a significantly larger area. The conditions under which this test is performed are related to the actual use of the v. By pumping fairy «Compared with H pressurization can reach a wider area of the buccal mucosa. 1. The specific implementation is better. The total amount of solvent and co-solvent in the formula (without propellant) is greater than 65% W / W, more preferably greater than 70% w / w, more preferably greater than 75% w / w, and more preferably More than 80% w / w, and more preferably more than 85% w / w. The total amount of solvent and co-solvent present in the two best formulations ranges from 8 g% w / w to ㈣ W / w. 0 Preferred solvents for this formulation are lower alkyl (C "C4) alcohols, most preferably ethanol. 'Preferred co-solvents for this formulation include propylene glycol, glycerol, macrogols, and also include A co-solvent that can be used as a solubilizer is preferably polyoxyhydrogenated castor oil. In the scope of the present invention, the "solubilizer" and "self-emulsifier" included in the formula can be the same chemical substance. In this case, the word "solubilizer" means that it prefers substances that increase the solubility of active ingredients (ie, lipophilic drugs) in the formulation. In the formulation of the first aspect of the present invention, a solubilizing agent may be included to overcome the solubility problem of an improved active ingredient (lipophilic drug) in a formulation containing a limited amount of ethanol. Adding solubilizers in this way usually has the effect of increasing the amount of active ingredients that can be blended into the formulation while maintaining patient tolerance. This paper size applies to China National Standard (CNS) A4

T. (Please read the notes on the back before filling this page) 1222882 A7 B7 V. Description of the Invention (11) The advantages of the co-solvent will be explained with reference to the formulation of lipophilic drugs containing one or more types of cannabinol. Cannabinoids usually have limited solubility in many solvents, which limits the amount of cannabinoids that can be blended into pharmaceutical formulations. For example, stabilizing 0.7 ^ THC / 0.1ml liquid formula containing ethanol plus propellant to aerosol spray. As a result, this formulation must be applied multiple times to achieve a medically meaningful dose of active cannabinoid. Adding a solubilizer, which is a better solubilizer than standard propellants, such as the teachings of the present invention, propylene glycol, glycerol, marke or polyoxygenated castor oil, can mix far larger amounts of activity into classified cannabinol, and it also says A pharmaceutically relevant dose of cannabinoid can be administered in a single administration of the formulation. Fortunately, in the specific embodiment, the formulation contains ethanol as a solvent and propylene glycol as a co-solvent. In this specific embodiment, the ratio of ethanol to propylene glycol in the formulation is preferably in the range of 4: 1 to 1: 4 and most preferably 丨: 1. In a further preferred embodiment, the formulation contains ethanol as a solvent, and polyoxyhydrogenated castor oil (optimally CMOFO RH40) as a co-solvent / solubilizer. In this specific embodiment, the amount of polyoxygenated castor oil present in the formula is greater than it * accounts for the total amount of polyoxygenated castor oil plus ethanol present in the formula (%, more preferably the total amount of polyoxygenated castor oil plus ethanol in the formula The amount w / w) is 50/50 to 55% w / w, more preferably 20% to 40% w / w, and most preferably 30% w / w. The total amount of polyoxygenated castor oil plus ethanol is up to 97% w / w of the formula. Appropriate self-emulsifiers that can be included in this formulation are listed in Table 2. The first aspect of the invention is described above. Most preferred are glyceryl monooleate and glyceryl monostearate (preferably self-emulsifying grades). In this formula, the total amount of self-emulsifier is preferably 10/0 higher than the formula. The paper size is applicable to China National Standard (CNS) A4 (21〇297mm) (Please read the precautions on the back before filling in this page)

• 、 I 14 1222882 A7 __B7 V. Description of the invention (I2) W / W. As explained previously, other excipients may be included in the formulation such as antioxidants, flavorings, and the like. The formulated formula does not contain any propellants, such as those commonly found in propellant-driven aerosol formulations. In a preferred embodiment, the liquid and gel spray formulations of the present invention are suitable for application to buccal mucosa. The results of the direct investigation revealed that in some cases, the application of the drug to the sublingual mucosa was limited, thus limiting the use of the sublingual. Some highly fat-soluble drugs (including cannabinoids and cannabis extracts) can only be dissolved into solutions by dissolving (mainly) non-aqueous solvents. These solvents such as propylene glycol, ethylene glycol (with or without diols), and solubilizers are medically acceptable, but when dripped or sprayed on the sublingual mucosa (depending on the concentration of ethanol) may produce a burning tingling sensation. The tingling sensation in turn causes reflex swallowing. As a result, a certain proportion of the dose may be swallowed as a result of stimulating swallowing reflexes. The proportion of the dose absorbed by GIT is more variable than that of oropharynx> Chen, which results in the change of absorption due to the first pass effect. These factors cause the drug's absorption to vary, which is presumed to be a sublingual route. Found that applying a solution or emulsion formula directly to the buccal surface, including the use of drops or preferably a pumping action spray, can solve the problem of first pass, and there are many other unexpected advantages as follows. (1) When aerosols are guided into the oropharyngeal cavity, particle mist escapes from the mouth to indicate drug loss. Avoid this problem by spraying directly on the cheek surface, away from the sublingual area. This problem can be more completely solved by using a pumping manually operated sprayer (pAS). PAS is operated at a low pressure to produce a spray with a large average aerodynamic diameter (for example, 15 to 45 microns), which can be guided to the buccal area rather than the sublingual area; ϊ The paper size applies the Chinese National Standard (CNS) A4 specification ⑵〇χ297 public transformer) —-—; (Please read the precautions on the back before filling this page), tr-1222882 A7 ---------- B7 _ i ^ (i3) ^ one ( 2) Prevent or minimize unacceptable tingling sensations (in this respect, the buccal mucosa is less sensitive than the sublingual area); () The dose of the drug on the K-brake to contact the buccal surface will prevent the drug from being positive $ Saliva secretion interferes with site absorption. After application, the buccal mucosa returns to its normal position on the surface of the gingival surface of the palate or chin, and is therefore held in the pocket that contacts the absorbent surface; (4) The loss of dose is minimized by swallowing. Application by cheek does not stimulate swallowing reflex. Because the drug is in a confined space, patients can choke normal saliva without disturbing the buccal pocket; (5) For cannabinoids, absorption by sublingual formula and buccal formula The area under the curve (AUC) is similar. After buccal administration, the content of major (11_hydroxy_) metabolites of cannabinoids decreased substantially. This confirms that the ratio of cannabinoid / active ingredient absorbed by the transmucosal region is higher than that of the sublingual area. After the buccal formulation described later (Reference Example 12) was used, absorption was higher from the buccal mucosa than from the sublingual mucosa. Purpose Drug Properties The examples below illustrate how sublingual and buccal formulations can be made from tricky lipophilic drugs such as cannabinoids or glyceryl dinitrate (GTN). However, the application of the present invention is not limited to such active ingredients. The following table illustrates some active ingredients with reference to their categories. Individual drugs can be formulated according to the present invention. If the drug is soluble in water, it can be dispersed in the oral epithelium and sublingual mucosa. If the drug molecule (after freeing) has an appropriate free constant, it will be absorbed into the systemic circulation through the epithelium. If the uncharged lipid molecules are in close contact with the mucosa, they will only pass through or through the oropharyngeal mucosa. ---------------- This paper size applies to China National Standard (CNS) Α4 specification (210X297 mm) _ ^

f:-. (Please read the notes on the back before filling this page).

May I 1222882 A7

5. Description of the invention (15) In the case of solvents, sugar alcohols are preferred. Therefore, according to the third aspect of the present invention-a sign, Chang 1 is for a pharmaceutical formulation for administration of lipophilic drugs, which contains at least one lipophilic fungus and at least one self-emulsifier, Wherein, when hydrated, the formulation forms a lipophilic drug-containing emulsion that can adhere to the mucosal surface and allow controlled release of the drug, wherein the lipophilic drug is at least one extract derived from a cannabis plant. "Drug extract" is an extract derived from plant material. The definition refers to the draft of the Plant Drug Product Industry Guide, August 2_, the US Department of Health and Human Services' Center for Food and Drug Administration, drug evaluation research. "Plant material" is defined as plants or plant parts (such as bark, wood, two leaves, flowers, fruit, seeds, berries, or parts thereof) and extruded products. The term "marijuana plant" encompasses wild cannabis (Cannabis sativa) and other crosses including Cannabis chemovars, which naturally contain various types of cannabis, and Cannabis sativa subspecies indica, including crosses var_indica and var_kafiristanica, Cannabis indica, and plants or their hybrids obtained by genetic interleaving and self-interleaving. The term “hemp plant material” shall be interpreted accordingly to cover plant material derived from one or more hemp plants. For the avoidance of doubt, the “cannabis plant material” described here includes dried cannabis biomass blocks. In the context of this case, the terms “cannabis extract” or “stroke derived from cannabis plant” are used interchangeably to cover “phytopharmaceutical substances” derived from cannabis plant material. Phytopharmaceutical substances in the phytopharmaceutical product industry refers to the 18 paper standards applicable to the Chinese National Standard (CNS) A4 specifications (210X297 mm) V. Description of the invention (16) Second draft, August 2_ 'US Department of Health and Human Services In the Food and Drug Administration: The drug evaluation study is defined as: "Derived from-or a variety of plants, the drug substance of steamed giant salamander. It is prepared from plant-based raw materials by the following-or multiple treatments: flour, fried Cooking, pressing, water-based extraction, alcohol extraction or other similar processes. " Botanical drug substances do not contain highly purified or chemically modified substances derived from natural sources. Taking cannabis as an example, the "phytopharmaceutical substance" derived from the cannabis plant does not contain a highly purified pharmacopoeia-like cannabis test. "Botanical drug substances" derived from cannabis plants include secondary extracts prepared using methods such as the use of solvents such as cuc5 alcohols (ethanol) 'Norfo blue (urfa) (HFAi34a), HF under pressure Then, the liquid carbon dioxide is subjected to an extraction process such as immersion extraction. -Sub-extractives can be further purified by supercritical or subcritical extraction, gasification and chromatography. When using, for example, the solvents listed above, the resulting extract contains a non-specific fat-soluble substance f. The fat-soluble matter f can be removed by a variety of methods, including the "winter" ° method, which involves quenching to _2OCc ', then passing through, removing bad debris, using liquid carbon dioxide extraction and steaming. Preferred "hemp extracts" include extracts obtained using any of the methods or processes specifically disclosed herein for preparing extracts from hemp plant material. The extract is preferably substantially free of wax and other non-specific fat-soluble substances f, but preferably contains substantially all cannabinol such as naturally occurring in plants, and Babe is the same proportion as it appears in whole cannabis plants. Plant-based drug substances are formulated as "plant-based drug products", a term used in the draft of the Plant-based Drug Product Industry Guide, August 2000, American Health

• Order, 0! (Please read the precautions on the back before filling out this page)) 5. Description of the invention (l7 2 The drug evaluation study of the Service Department, Food and Drug Administration Center is defined as a plant product prepared for use as a drug; A medicinal product derived from a botanical drug ". According to a fourth characteristic aspect of the present invention, a pharmaceutical formulation for administering a lipophilic drug via a mucosal surface is provided, the formulation comprising at least one lipophilic drug 至 and J a self-emulsifier Wherein, when hydrated, the formula forms a lipophilic drug-containing emulsion that can adhere to the surface of the mucosa and allow controlled release of the drug, where the lipophilic drug contains a combination of two or more natural or synthetic cannabinoids In this specific embodiment, the "cannabis-like compound" may be a highly pure classic grade f, which is purified from natural sources or obtained through synthetic means. The quasi-like compounds include, but are not limited to, tetrahydrocannabinol, its precursors, Alkyl (especially propyl) analogs, cannabidiol, precursors, alkyl (especially propyl) analogs, and cannabinol. In a preferred embodiment, the lipophilic drug package Any combination of two or more types of cannabinols, which are selected from the group consisting of tetrahydrocannabinol, δ9_tetrahydrocannabinol, Δ9-tetrahydrocannabinolpropyl analogs, cannabidiol, cannabidiol Propyl analogs, cannabinol, cannabinolene, cannabinol allyl analogues and cannabigerol. Suitable formulas for the administration of cannabis extracts and cannabinoids are also suitable for their use Drugs such as biological tests, tests and acids. The requirements are that if the drug is insoluble in saliva, it needs to be dissolved and / or adjusted to a suitable non-free form by adding buffer salts and [3] ^ regulators. The formula of the invention can be used for delivery Cannabis plant extracts also deliver individual 1222882 A7 _________ B7_ 5. Description of the Invention (18) " ~ ^ Cannabinoids, or their synthetic analogs, whether derived from a cannabis plant and a combination of cannabinoids. "Cannabis plant" includes wild cannabis and its variants, including Chimo cannabis, which naturally contains unequal amounts of various cannabinoids. In particular, the present invention provides cannabis-based medicinal extract (CBME) formulations. Hemp is used as a medicament For years, it was widely used as a prescription drug component in the Victorian era. Cannabis was used as a hypnotic tranquilizer for the treatment of "hysteria, insanity, epilepsy, neurological insomnia, migraine, pain, and dysmenorrhea." Cannabis continued to be used until 20 In the middle of the century, cannabis was being re-evaluated as a prescription drug today. It was found that specific cannabinol receptors and novel methods of administration can extend cannabis-based drugs to historical and novel indications. Cannabis is used for entertainment Prompted legislation results in banning marijuana. Historically marijuana has been considered a unique item by many doctors; it can be used to combat pain that is resistant to opiates, for conditions such as spinal cord injury and other forms of neuropathic pain including multiple sclerosis Pain and cramps. In the United States and the Caribbean, cannabis grown for recreational purposes has been selected to allow cannabis to contain high levels of tetrahydrocannabinol (THC) without sacrificing other types of anabol. In Merck Bow 1 (1996), other types of cannol known to occur in cannabis such as cannabidiol and cannabinol are considered to have no recreationally active ingredients. Although cannabidiol was previously regarded as an inactive ingredient, evidence shows that it has pharmacological activity, which differs from THC in several respects. The efficacy of cannabis cannot be satisfactorily stated simply with one or other "active" ingredients. It has been shown that tetrahydrocannabis (THC) alone is equivalent to THC as cannabis_1 1 " ...... 丨 丨 ·· '_ This paper size is applicable to China National Standard (CNS) A4 specification (210X297) ) _ ?1

-m (Please read the precautions on the back before filling out this page) Order — 1222882, Description of the invention The pain relief is lower when the extract is administered. The basic pharmacological basis of this phenomenon has been studied. In some cases, THC and cannabidiol (CBD) have the opposite pharmacological properties in the same g product bed rhyme test, and they have the same effect in the dagger test. For example, in some clinical studies and reports from Art Literature, it is felt that CBD can modify the psychological effects of THC. The range of activity of the two types of cannabinol helps to illustrate some of the therapeutic effects of several cannabis grown in different regions of the world. It is also pointed out that the combination of THC and CBD can produce useful effects. Researched by applicant. Table 3 below shows the differences in pharmacological properties of the two cannabinoids. 22 (Please read the precautions on the back before filling in this page} This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 B7 V. Description of invention (20) Table 3 Effect THC THCV CBD CBDV Reference CBi (brain receptor) ++ To Pertwee et al., 1998 CB2 (peripheral receptor) +-CNS anti-convulsant + + ++ Carlini et al., 1973 Antimetrazol--GW data anti-shock- ++ GW Data Muscle Relaxant-Petro, 1980 Photosensitizer ++ + GW Data Ankylosing Syncope ++ -H- GW Data Psychoactive ++-GW Data Antipsychotics-++ Zuardi et al. 1991 Neuroprotective Antioxidants + ++ Hampson AJ, 1998 Activity * ++-Antiemetic + + Sedative (reduces autonomic activity) Zuardi et al., 1991 Stimulate appetite ++ Suppress appetite-++ Anxiety GW data Cardiovascular effects Slow heart rate-+ Smiley Et al., 1976 Acceleration +-Hypertension § +-Lowering blood pressure §-+ Adams et al., 1977 Anti-inflammatory soil Brown, 1998 Immunomodulatory / anti-inflammatory activity Protopodal edema test Test-+ GW data Coxl GW data Cox2 GW data TNFa antagonist + + ++ ++ glaucoma-Η-+ .................. #!-*-· (Please Read the precautions on the back before filling in this page) • Order, * The impact has nothing to do with 〇61 receptor + THC is a pre-convulsant § THC has a biphasic effect on blood pressure; in the first-time use of patients, THC produces postural hypotension, and Low gold pressure is generated when the report is used for a long time. GW International Report No. 002/000159. 23 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 B7 V. Description of the invention (21) The characteristics and the results of experiments performed directly by the applicant have unexpectedly shown that the combination of THC and CBD in varying proportions is particularly useful for treating certain medical conditions. It is further found that the toxicity of a mixture of THC and CBD is clinically lower than that of THC alone. In a fourth characteristic aspect, a pharmaceutical formula containing cannabinoids is provided, which has a specific ratio of CBD to THC, and is found to be clinically useful for treating or treating a specific disease or medical condition. In yet another characteristic aspect, the present invention also provides a pharmaceutical formulation having a specific ratio of sub-tetrahydrocannabinol (THCV) or sub-cannabinol (CBDV). THCV and CBDV (propyl analogues of THC and CBD, respectively) are cannabinoids known to be mainly expressed in specific varieties of cannabis plants. It was found that THCV has qualitatively superior properties than THC and CBD, respectively. People who take THCV report that THCV produces fewer emotional lifts than THC. The number of severe hangovers also decreased. In yet another characteristic aspect, the present invention provides a pharmaceutical formulation having a specific ratio of THCV to THC. This formulation was found to be particularly useful in the areas of pain relief and appetite irritation. In a preferred embodiment, the formula provided according to the fifth and subsequent features of the present invention, such as a formula containing a specific type of cannabinol, also has important characteristics of the "self-emulsifying" formula described above. The present invention also provides a method for manufacturing the aforementioned pharmaceutical formula, and a method for treating or treating a specific disease or condition using the pharmaceutical formula. The formulation, method and use of the present invention are set out in the scope of the accompanying patent application. The applicant in this case observed in particular that the combination of specific cannabinoids was 24 (please read the precautions on the back before filling this page) This paper size applies to China National Standard (CNS) A4 (210X297 mm)

2. Description of the invention (22) Any individual cannabinoid is more advantageous. The preferred embodiment is a formula in which the CBD content is higher than the THC content. This formula is called an "inverse proportion" formula. This formula is novel and unusual. The reason is that among various varieties of medicinal and recreational cannabis plants available worldwide, CBD is a secondary cannabinoid-like component compared to THC. In other specific embodiments, THC and CBD or THCV and CBDV are approximately equal. Or THC or THCV is the main component and accounts for up to 95.5% of the total amount of cannabinoids. Special examples of the target medical conditions suitable for use are shown in Table 4 below. ---------- ------------ # ----- < 4 (Please read the precautions on the back before filling out this page) Table 4: Different types of cannabinols compared with the products of the agricultural border therapy group Different THC: CBD ratio Target treatment area high THC > 95: 5 Cancer pain, migraine, appetite stimulation ratio 50:50 Multiple sclerosis, spinal cord injury, peripheral neuropathy, other neurogenic pain anti / wide ratio CBD < 25:75 Rheumatoid arthritis, high CBD with inflammatory bowel disease < 5: 95 ^ 神 = (, Schizophrenia), epilepsy or dyskinesia Ϊ 苴; 殳 Second injury, rheumatoid arthritis ^ The course of the disease modifies appetite suppression

I. The pharmaceutical formula of the present invention can be formulated from pure cannabis-like combinations and well-known pharmaceutical carriers and excipients. For example, CBD and THC can be purchased from Sigma-Aldrich Company, Puduoyi, Fanxi Road, Yuan 2 4QH. CBDV and THCV are derived from cannabis plants using techniques well known to the artisans. The use of cannabis plants and cannabinoids in certain areas requires government approval ', but the government has approved institutions for medical research and commercialization of drugs. The UK's approval certificate can be applied to the "Family Office. In a preferred embodiment of the present invention, the formula sentence eight | 上 — Wbar contains one or more cannabis paper This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297) (%) 25 1222882 A7 __B7__ 5. Description of the invention (23) Extracts of whole plant varieties, especially wild cannabis, Indian cannabis or plants obtained by genetic interleaving and self-interlacing or their hybrids. Exact cannabinoid content of various specific cannabis variants It can be determined qualitatively and quantitatively using methods well known to those in the industry, such as TLC or HPLC. In this way, the extract can be prepared to obtain a cannabis variant with a predetermined ratio of CBD to THC or CBDV to THCV or THCV to THC. Alternatively, The extracts obtained from two or more different variants are mixed or blended to produce a material with a better ratio of cannabinoids that can be formulated into a pharmaceutical formula. The preparation of convenient ratios containing THC- and CBD_ drugs can be prepared by Cultivation of specific chima variants of marijuana was achieved. Such chima variants (differentiated by cannabinoids produced rather than by morphological characteristics of plants) Strains) have been bred through a variety of plant breeding techniques familiar to skilled artisans. The production of materials by plugging propagation plants can ensure that the genotype is maintained and thus ensure that each plant harvest contains a substantially equal proportion of cannabinoids. In addition, it has been found that through horticulture Selection methods can also obtain other Chimo variants whose cannabinoid-like content is mainly represented by hypotetrahydrocannabinol (THCV) or subcannabinol (CBDV). As far as horticulture is concerned, it is convenient to produce THC by plug growth, THC V, CBD and CBDV are the main variants of cannabis-like chimeras. This ensures that the genotypes of all plants are exactly the same, and the qualitative formula (the proportion of various cannabinoids in biological substances) is exactly the same. Therefore, the variants of chimera use similar extraction methods Extracts can be prepared. Convenient methods for preparing a single extract include immersion, diafiltration, C1 to C5 alcohols (ethanol), Norfolk Blue (HFA134a), HFA227, and liquid dioxide. Pressure extraction. A single extract can be further extracted Purification, for example, the size of this paper exceeds the Chinese national standard A4 specification (210X297 mm) 26 (Please read the back first Note for refilling this page), ^ τ— V. Description of the invention (24) Critical or subcritical extraction, gasification and purification of chromatography. When the solvents listed above are used, the resulting extract contains heteropure lipids Soluble substances. Non-specific fat-soluble matter f can be removed by a number of treatments, including quenching to -20 t and then filtering the silk-like debris, carbon dioxide extraction and removal by evaporation. The preferred plant cultivation and extract preparation methods are shown in Example. The obtained extract is suitable for mixing in pharmaceutical preparations. The method of administration can be sublingual drops, sublingual tablets, gels and sprays, aerosol inhalers, gasifiers, and other conventional pharmaceutical oral dosage forms. Intestines and rectal suppositories. Other possible formulations are cited in the patent attached to the towels attached to Ik. Preferably, the extract is formulated into a self-emulsifying formulation according to the first and second characteristic aspects of the present invention. These routes of administration have their own advantages and disadvantages. Formulations usually administered via the respiratory, oral / nasal and distal rectum avoid the first-pass effect of the liver. The swallowing drug undergoes actual metabolism when it passes through the liver for the first time, and the type of metabolite produced may change depending on the route of administration. There are many medical conditions that can be effectively treated with cannabis. The proportion of different cannabis in this preparation determines the best medical condition to be treated, and the present invention solves the formulation problem that is most suitable for this project. As mentioned above, the teaching of the present invention will be illustrated by the use of a preparation containing a specific proportion of cannabis (Table 4) 'and will be further illustrated by examples. Direct experiments have shown that administering cbd (or CBDV) before administering THC can modify the effect of consciousness. Minimizing the psychic effects of THc ’will delay and moderate the sedative effect subsequently. This reduction effect cannot be observed if THc is administered before ⑽. As such, one of the preferred embodiments of the present invention is-medicinal lozenge for buccal or sublingual administration, which has a layer of fast dissolving 1222882 V. Explanation of the invention (25) solution of CBD or CBDV, and the second layer or core layer dissolving Less fast THC or THCV. The formulation thus provides a means of absorbing the drugs in a timed sequence. It is indeed possible to formulate a variety of two-phase formulations with modified release profiles. The applicant of this case further observed that the CBD can be used as a pharmaceutical tincture for pharmaceutical formulations, thus prolonging the storage life. Without wishing to be bound by theory, it is believed that the reason may come from the antioxidant properties of the CBD. Although it is known that the antioxidant properties of cbd can be used for the pharmacological design of living substances, it has not previously been observed to be effective as a drug stabilizer. Thus, in another feature aspect of the present invention is the use of cbd to extend the shelf life of a medicinal product containing one or more biologically active components. The composition of the better biological activity is stated in the scope of the attached patent application and belongs to one or more of the drugs and specific drug categories shown in the table above. Brief description of the drawings The present invention will be further understood with reference to the following examples together with the accompanying drawings, in which: Figure 1 schematically shows the packaging of a dosage form according to the present invention. Figure 2 shows schematically the application of a dosage form according to the invention to the palatal fossa. Figure 3 schematically shows the dosage form in place. Figure 4 shows schematically the mucosal staining that is typically observed after the dosage form has been in place for one minute. fExample 1 A 10% pregelatinized starch solution (component A) was prepared. One part of the powdered pregelatinized starch was dispersed in 9 parts of water, heated to gelatinization, and then cooled. Pregelatinized corn starch This paper is in accordance with Chinese national standard (〇 ^) A4 size (21〇 < 297 mm) 28 V. Description of the invention (26) Powder is the subject of a national prescription-level single chapter in the United States. This product is used as a component of other formulations listed in the examples below, and is referred to as "starch gel". With negative surface charge. ZM1 Next, the preparation of the formulation of the present invention is described, in which a hop extract is used, which is an oily resin-containing substance used as a substitute for an active ingredient. It has a bitter taste, so when the active ingredient stimulates the taste buds and implies the active ingredient-mucosal parent interaction, the patient is immediately discernible. The distribution of the formula on the cheeks and sublingual mucosa is shown by color development. The patient's increased desire to swallow the formula is measured by direct observation. In this example, the formulation is made by combining a gel (containing at least one active component with a negative surface) with a gel having opposite surface charges. The oppositely surface-charged gel may optionally contain at least one active ingredient that may be the same as the oppositely-charged gel or other active ingredient. When two gels with opposite surface charges contact together, agglomeration occurs, resulting in a change in viscosity, but the resulting gel is still thermoplastic and can still be used in the mold. When cooled, the gel fixed to a flexible but rigid gel. Sugar gelatin is prepared by heating 18 parts of bovine or pig gelatin or fish gelatin (fish gelatin) and glycerol, and heating it on water cooling with distilled water sufficient to make a final weight of 100 parts by weight. The sugar gelatin thus produced is a transparent rigid gel, which is unexpectedly stable. It is resistant to attack by microorganisms and is in equilibrium with air relative humidity of 60-70%. Prepare a formula from ...

This paper size applies Chinese National Standard (CNS) A4 (210 X 297 mm) 1222882 A7 B7 V. Description of the invention (27) Glyceryl monostearate (SE) Soy egg filling chlorophyll (oil-soluble) Group A Fermentation BP hop extract extract sugar gelatin 5 parts 7 parts 3 parts 30 parts 0.1 parts 10 parts 100 parts mixture to stir and heat to 9 (rc temperature (using a water bath or microwave oven). The mixture is thoroughly stirred and then still melted Mix 2 grams of each part into an aluminum foil mold that has been treated with a release agent. Some release agents are suitable for this purpose. Polylithium oxide or bee sacrifices a solution of n-hexane to spray the concave mold to let the solvent Evaporate to dryness. The weight of the finished product can be changed to accommodate up to about 250 grams of cannabis, which means it contains about 150 mg of THC or CBD. When cooling, the laminated foil is placed on the mold and sealed by heating. The air is evacuated and replaced by vacuum. The nitrogen formation is performed before sealing, so the residual space of the completed unit dosage form becomes an inert non-oxidizing atmosphere. The product thus produced is a long | 卩 -shaped gel with a convex surface and a frank surface. It contains oil-soluble Agent, indicating the distribution pattern of the emulsion in the mouth. This chlorophyll as a revealing agent is a feature that can be used as needed; when using chlorophyll, it indicates the area of the buccal mucosa containing the drug product. The features of the present invention are illustrated in Figures 1-4 It is obvious to those skilled in the art that the physical shape and form of the emulsifier in the package are also within the scope of the teaching of the present invention. TMl The aforementioned formula produces an elastic but rigid gel product. When the half key is placed on the upper side of the oral cavity The medial (superior palatal sinus) half-ingot is leveled and placed in one minute (please read the precautions on the back before filling this page). This paper size can be adapted to the CNS A4 specification (210X297) (28 mm) V. Description of the invention (28) J mouth melted and two knives. J Lichen has produced an emulsified substance covering the buccal mucosa. When placed on the upper cheek and buccal adhesion, the gel does not have any sensation, nor does it induce temptation. The need to swallow the agent. The covered buccal mucosa area can be confirmed before administration, 1 minute, 2 minutes after giving music, such as TZ 1 Γν \ Dao Lili and 10 Li Zhong or other convenient time photography records. This formulation is slightly characterized by chlorophyll taste. After placing the gel in place, it can be identified as a hop extract for as long as 10 knives. This confirms the existence of a "controlled release drug" in the oropharynx during this period. The distribution of color (1 minute ㈣, taste lasts up to 1G minutes) indicates that this type of formula is suitable as a vehicle for the administration of highly fat-soluble drugs such as cannabis extract or marijuana-like drugs. Tune can be used in clinical trials as a self-indicating safety The agent preparation. The figure indicates-the distribution of the semi-product in σ. The configuration of the product and the distribution area of the product during in-situ emulsification are shown in Figure 丨 _4. Figure 3 shows the original placement of the device. For clarity, the display product is placed on one side of the mouth. However, it can also be placed equally on both sides to ensure maximum distribution. Alternatively, products containing different active ingredients can be placed at the same time but in the mouth twice. Example 4 The device of Example 1 was sandwiched between two nylon meshes and attached to an ingot distribution equipment monitor (designed by BP) at 35 ° C. The gel is dispersed within 2 minutes to form a fine and uniform emulsion. Example 5 This example relates to the preparation of a dosage form containing a mixture of cannabis extracts. For convenience, the cannabis extract is referred to as cannabis-based medicinal extract (CBME). Obtained from a total of more than 90% of the cannabinoids that can be produced are cannabis. 1222882 A7 B7 V. Description of the invention (29) (Please read the notes on the back before filling this page) (CBD) The cannabis variant of the cannabis is super Critical fluid extraction of dried cannabis preparation. Called CBME-G5. Similarly, an extract with a high proportion (over 95%) of total cannabinoids is tetrahydrocannabinol (THC), which is called CBME-G1. The formula of this example can be modified to accommodate CBME containing larger or lesser amounts of cannabinoids, so as to achieve the desired THC to CBD and other cannabis ratios. Products containing different ratios of THC to CBD can be used to treat specific medical conditions. Mixture is made by melting the following ingredients: glyceryl monooleate 10 parts soybean egg fat 10 parts curcumin 0.1 part composition A 20 parts CBME-G5 obtains CBD 1 part CBME-G1 obtains THC 2 parts α-tocopherol 0.1 part ascorbic acid Base palmitate BP 0.1 parts sugar gelatin to make 100 parts of each component are gently heated on a water bath, mixed, stirred, and poured into a mold while hot. The product in the mold was completed as in Example 1 and sealed under an inert gas. In this formula, curcumin provides a bright yellow color to make the product distinguishable in the area of the mouth. Alpha-tocopherol and ascorbyl palmitate are antioxidants, which can be combined with glyceryl oleate to obtain an effective antioxidant system. The size of this dosage form is quite large (1-2 grams), and a large amount of active ingredients can be mixed in the dosage form. The dosage of cannabidiol is 900 mg / day, and the dosage form allows this dose to be divided into 2-9 (preferably 2-4) doses per day. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -32-A222882 5 parts 0.5 parts 79.3 parts 10 parts 5 parts 0.1 parts 0.1 parts 10 parts, the invention description (30) In terms of w / w, tetrahydrocannabinol is more active than cannabinol. If a smaller unit dose (THC) is required, this dose can be included in a conventional sublingual tablet. Example 6 illustrates this lozenge formulation. Monostearic acid glycerol vinegar (self-emulsifying grade) Polysorbate 80 lactose (direct compression grade)

Soluble powder tetrahydrocannabinol ascorbyl palmitate purpose OC-tocopherol (dehydrated) BP monoglyceryl stearate, polizobe, ascorbyl palmitate, cardanol and THC disperse in alcohol . The alcohol solution is spray-dried on the thoroughly dry powder ingredients. The ethanol was allowed to evaporate, the granules were sprinkled with 1% talc and compressed in a conventional tableting machine to a target tablet weighing 101 mg. Biconvex punches with a diameter of 7 mm or s pen meters are used to make lozenges with a high surface / weight ratio. Lozenges absorb water when placed in contact with the sublingual or buccal mucosa. The dissolution rate can be adjusted by changing the degree of compression. The ingots compressed to __3 Newton pressure were dispersed over a period of one minute. The disintegration was measured by the method described in Example 4. The disintegration time of this ingot was less than 4 minutes. Example 7 The production of emulsions from self-emulsifying formulations is not limited to solid dosage forms. The examples below illustrate three liquid formulations suitable for sublingual use. The following ingredients (quantity expressed in parts by weight) are melted together (temperature does not exceed 50.0) to produce a solution ... This paper size applies the Chinese National Standard (CNS) A4 specification (210 × 297 public directors) 33 (Please read first (Notes on the back then fill out this page)

1222882 A7 B7 V. Description of the invention (31) ABC glyceryl monostearate (self-emulsifying) 2 2 2 medium chain triglyceride 5--CMOFO RH40 30 26.5-CBME 10 10 CBME-G1 obtained THC 5 CBME -G5 Obtain CBD 5 α-Tocopheryl 0.1--Ascorbyl palmitate 0.1--Propanediol--44 Ethanol BP 52.8 61.5 44 Total 100 100 100 (Please read the notes on the back before filling this page) Mix the ingredients The obtained product was sealed in a glass vial with a volume of 10 ml and closed with a pump spray opening button. Each 1 ml of the product contained 100 mg of THC. Each time the pump was pumped, a fine spray could be delivered directly to the sublingual mucosa Area. CBME alone in ethanol solution is generally not suitable as a spray. The irritating nature of pure ethanol solvents often limits the amount of mucosa that can be applied to it, as it may cause discomfort to the patient. The unexpected addition of self-emulsifying primary surfactants and solubilizers will allow a unit dosage form to contain larger amounts of cannabinoids. Spraying a small amount on the sublingual or buccal mucosa results in a considerable amount of ethanol evapotranspiration. The emulsion thus produced is not irritating and will not stimulate swallow sigma reflex. This provides a long-term formation of the emulsion in contact with the sublingual or buccal mucosa. The special feature of this formula is the solubilizing activity of medium-chain triglycerides, and it also acts as a secondary emulsifier. The viscosity of the above formula "B" is in the range of 100-350 centipoise. Example 8 34 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 B7 V. Description of the invention (32) The solid dosage form can be a soft gelatin capsule, which can be crushed to release the drug to obtain an emulsion. The capsule is then swallowed to allow the remaining dose to be absorbed in the rest of the gastrointestinal tract. Soft gelatin capsules are available in pharmaceutical emulsified form and can be absorbed by any part of the gastrointestinal tract. Capsule material can be prepared from the following ingredients: glyceryl monostearate (self-emulsifying) 5 parts Polisobe 80 1 part beeswax 5 parts CBME G1 obtains THC 10 parts CBME G5 obtains CBD 10 parts α-fertility 0.1 · 1 ascorbic acid group 100 parts by weight of palmitic acid, 0.1 part of hop oil, Example 9 Cheek preparation using vegetable gelling agent instead of animal gelling agent: Sorbitol 35 parts Gum Arabic 20 parts Glyceryl monooleate 10 parts Phosphorus _ 10 parts of CBME-1, 5 mg of THC, 5 parts of CBME-5, 5 parts of CBD, 5 parts of tocopherol, 0.1 parts of ascorbyl palmitate, 0.1 parts of vanillin, 0.1 parts of BHT, 0.01 parts of glycerin, 5.0 parts of water, and 35 parts of water (read first Note on the back, please fill in this page again) This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 _____ B7 V. Description of the invention (33) Months> Valley ingredients at 70 ° C '丨Grain together. Sorbitol is mixed with labber gum, dispersed in glycerin, and added to other solid ingredients. Add water and heat the material on the Buddha's water bath to disperse / dissolve uniformly. Distribute the substance in the mold while at 6 (rc temperature (as described in Example 1). The substance can also be cast or rolled into thin slices, preferably 2.5 mm thick. Cut an oval or hexagonal block of 40 mm area ' Each piece is applied to a non-adhesive liner that is larger than the piece, and is covered with a non-adhesive protective film. The patch thus formed is sealed in a pocket made of heat-sealable laminated foil under an inert gas atmosphere. The product thus manufactured Suitable for treating patients with migraine, arthritis, epilepsy, multiple sclerosis and other types of neuropathic pain and neurogenic pain, requiring drug release for up to 丨 hours. The disintegration time of this formula is greater than 90 minutes. Example 10 Obtaining the ingredients The product of rapid release and further long-term release of other ingredients can be obtained by combining unit dosage forms. Using the formulation described in Example 8, the quantitatively heated substance is filled into a mold or cast into a film to harden. Then a layer of Example 5 The material was cast on the gelatin surface described in Example 9. Then the composite gel was packaged as described in this example. The unit ratio of the two layers can be changed to obtain this unit. Modification of the kinetic profile of the type. In some cases it may be desirable to administer two drugs in a time-dependent order. One of the paired drugs appears to have a protective effect on the other. Example 10—The compound described in the previous example Gel formula. The formula described in Example n provides CBD, which is an antioxidant and has a protective effect on THC, so it can be absorbed through the buccal / sublingual mucosa just before THC. Hemp II is contained in the fast-release layer ' THC is dissolved by the delayed release layer. Example n shows that there are different ^ paper standards for financially appropriate family standards (⑽) Erge (2 songs 297 public) -----

Tri (please read the notes on the back before filling this page) 1222882 A7 B7 V. Description of the invention (34) A unit dosage form consisting of two layers of dissolution characteristics. Example 11 Glycerol monooleate, 7 parts soybean egg fat, 7 parts gum arabic, 15 parts tetrahydrocannabinoid, 10 parts α-tocopherol, 0.1 parts xylitol, 5.1 parts glycerin, 3 parts pure water, and 100 parts (read first Note on the back, please fill in this page again.) Molten material is manufactured as in the previous example, and the entire part is cast or cast into thin pieces in a mold. (b) Glycerol monooleate 15 parts Soy egg filling 10 parts Component A 20 parts α-tocopherol 0.1 part cannabidiol 20 parts Sugar gelatin 100 parts The mass was prepared as described in Example 2. The mass is cast as a second layer in a mold containing a portion of formula (a). At the interface, the two components are slightly melted and welded to form an adhesion product. If the gel is cast on a concave mold, the product has a flat surface, which first disperses when it comes into contact with the mucosa, so that the absorption sequence of each component is generated. A layer of formula (b) can be cast on the surface of the sheet of formula (a). Both formulations contain a colloidal component, with oppositely charged signs, and produce good adhesion by agglomeration in the melting section. The composite layer is then cut into a shape suitable for application to the oral mucosa. The product is packaged and protected from air and light as shown in Example 3. 37 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7B7 V. Description of the invention (35) Example 12 The following example illustrates the unique features of the formula intended for spray application to the buccal mucosa and its application method 2. Compare the blood concentration produced by sublingual administration via buccal absorption. The following are examples of liquid formulations suitable for buccal administration. A solution is made by dissolving (temperature does not exceed 50 ° C) the following ingredients (quantitative details are expressed in parts by weight ratio): abcde glyceryl monostearate (self-emulsifying) 2-2-2 glyceryl monooleate (self-emulsifying )-2-2-Cmorford RH40 20 30 30 20 30 CBME-G1 obtained THC 5 10---CBME-G5 obtained CBD--5 10-CBME-G1 and G5 obtained THC & CBD----each 10 Alpha-fertility 0.1 0.1 0.1 0.1 0.1 Ascorbyl palmitate 0.1 0.1 0.1 0.1 0.1 Manufacture of ethanol BP 100 100 100 100 100 Hemp-based medicinal extract (CBME) is a cannabis extract. Its preparation method is, for example, using liquid The carbon dioxide is immersed, the debris is removed by cooling the concentrated ethanol solution to a temperature of -20t, and the precipitated inert plant components are removed by filtration or centrifugation. A product made by mixing the ingredients was prepared in a 6-ml portion in a glass vial and sealed with a pump-operated sprayer. When used, the dose is emitted by a dispersing button or a conventional design. A suitable device suitable for this project is the VP7 type manufactured by Faros, but similar designs are available from other manufacturers. The vial can be enclosed in a secondary package to allow the spray to be directed to the buccal mucosa specific 38 (please read the precautions on the back before filling this page) This paper size applies to China National Standard (CNS) A4 (210X297 mm) 1222882 A7 — —___ B7 V. Description of Invention (36) area. In addition, a special button with an extension can be used to guide the spray to the preferred area of the buccal mucosa. Each 1 ml product contains 50-100 g of A9-tetrahydrocannabinol (THC) and / or cannabis hope (CBD). The spray is delivered with each actuation of the pump, and the spray can be directed to the buccal mucosa. CBMEs with known cannabinoid-like strength were used in the aforementioned formulations. CBME-G1 is a high-yielding cannabis strain derived from THC, = CBME-G5 is a high-yielding variant of CBD. It is obvious to those skilled in the art that purified cannabinoids and extracts derived from cannabinoids can be formulated by quantitative adjustment as described above. Although CBME alone can be used as a spray in ethanol solution, the amount of cannabinoid delivered is limited by the irritating properties of high concentration pure ethanol as a solvent. Such restrictions limit the amount that can be applied to the mucosa without causing patient discomfort. One group of patients received THC or CBD in the aforementioned type of solution, and guided the mouth mist to the sublingual or buccal mucosa. The patients consistently reported a tingling sensation when administered sublingually, but not when the solution was sprayed on the buccal mucosa Discomfort or mild discomfort. It was further unexpectedly discovered that the addition of a self-emulsifying primary surfactant as a solubilizer would allow a unit dose to contain a greater amount of cannabinoid. Spray a small amount of this formula onto the buccal mucosa without causing noticeable irritation of swallowing reflexes. This provides that the emulsion formed in situ contacts the cheek surface for a longer dwell time. The formulation was administered to a group of 13 patients who received 4 mg THC, 4 mg CBD, or placebo (single vehicle) via sublingual tablets, sublingual pump spray, or buccal route. The absorption of cannabinoids and primary metabolites [area under the absorption curve (AUC)] was determined by taking blood samples after administration. The following table lists the normalized averages. This paper size is in accordance with Chinese National Standard (CNS) A4 specification (21〇χ297mm) 39 ----- *-(Please read the notes on the back ^ before filling in this page) • 、 一 -T— 1222882 A7 B7 V. Description of the invention (37) Plasma analyte PAS Sublingual sublingual tablet Administration route Oropharynx AUC AUC AUC THC 2158.1 1648.4 1575.0 11 OH THC 3097.6 3560.5 2601.1 CBD 912.0 886.1 858.0 Results show sublingual and buccal (oropharyngeal) The total amount of cannabinoids absorbed by the pathway is similar, but the level of 11-0H metabolites detected by the oropharynx (cheek) after administration is substantially reduced (about 25%). This finding stems from inconsistent metabolism of buccal formulations to reduce swallowing (and subsequently liver). It is known that the THC 11-hydroxy metabolite has a higher psychoactive activity than the parent compound. It is therefore desirable to reduce the amount of such metabolites during administration, and this project can be achieved by using formulations and application methods that reduce swallowed buccal or sublingual doses. The pump action spray is obviously an effective way to reduce the amount of metabolites absorbed from the gastrointestinal tract by swallowing below the height of the oropharynx. Example 13 Using a pump action dispenser, a specific amount of gel can be dispensed with the required accuracy and drug reproducibility. The gel is prepared from the following ingredients (parts by weight): sodium carboxymethyl cellulose 2 glycerol stearate 10 glycerol 10 CBME-G1 and G5 obtains THC and CBD 5 ethanol 40 ascorbic acid 0.1 tocopherol 0.1 water Add to 100 40 (Please read the notes on the back before filling in this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 B7 V. Description of the invention (38) Non-aqueous ingredients are not too high Melt at 50 ° C until uniformly suspended. Then add water to make a viscous cheese-like gel. Be careful not to introduce air when mixing. The product is dispensed in the container while it is still warm and sealed with a pump dispenser head (25 1/33 1 type). It is provided by Faros. The head of the mixer device can send out a gel, and when the pressure is released, the gel is fully retracted to ensure that the gel particles are not exposed. The dosing gel is guided to the buccal surface and adheres to it. When the buccal surface returns to its normal position, the gel substance absorbs a larger amount of water from the saliva to obtain its drug charge. Example 14 The experiment showed the effect of changing the content of self-emulsifier and the ratio of negatively charged and positively charged tackifiers on oral dissolution / disintegration time. The solid gel formulations described in Examples 1 and 2 were obtained by heating the ingredients in a winter drink oven to obtain a homogeneous molten mass. The molten mass was directly blended into a recovered plastic cell using a Gibson burette, which was washed and air-dried with 70% alcohol. The disintegration time was measured on a BP device. The impact is explained as follows: With the increase of the mass, the disintegration time is extended: G001 / A (i) G001 / A (ii) GOOl (iii) Mass (mg) 586 807 2140

Tdis (m, s) 920 1230 2110 Increased emulsifier content can prolong Tdis:

G001A G001B% emulsifier 10 20

Tdis 1345 8730 41 (Please read the notes on the back before filling out this page) This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 1222882 A7 B7 Description of the invention (39) Increase the gelatin content of the gel to Tdis The effect is minimal: G001 / A G001 / B mass (mg) 1145 807% gelatin 14 25 Tdis 1345 1230 Adding pregelatinized corn starch (PGMS) reduces Tdis: G002 / A (ii) G003 mass (mg) 807 751% PGMS 0 2 Tdis 920 405 (Please read the notes on the back before filling out this page) This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 42 1222882 A7 B7 V. Description of the invention (4〇) Table 1: Examples of drugs that can be included in the formulations of the invention. Drug Category Drug Example Belladonna atropa contains bioassay-rich extracts and other 5 lycoris species (Gallanthus spp.) Contain bioassay-rich narcissus species (Narcissus spp.) Bio-extract-rich opioid-rich morphine cocaine Daimorphine pomaceae-rich alkaloid-rich extract pilocarpine salicylate anti-asthma terbutaline antifungal antifungal agent Fluconazole Anti-inflammatory agent Benzidamine Pyroxicam Antiviral agent Acyclovir Zidovudine Beclomethasone Wild cannabis and India Cannabis and its derivatives of Chimo variants are rich in cannabinoids. Some cannabinoids are Δ9-tetrahydrocannabinol (THC). Cannabis—CBD. Cannabinol (CBN). The most abundant composition of cannabinoid-rich partial cardiovascular agent Nifedipine Diltiazem Verapamil Central-acting analgesic Butorphe nol) Buprenorphine Fentanyl anti-angina pectoris Flut icasone propionate polyunsaturated fatty acid triglycerides n-3 and n-6 PUFAs S & Glycerol-like sympathomimetic amine Salbutamol (Please read the precautions on the back before filling this page) 43 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 1222882 A7 B7 V. DESCRIPTION OF THE INVENTION (41 Compound classes are shown in bold type. Compound examples are intended to illustrate and not limit the invention. Those skilled in the art understand that compounds with unit dosages less than 10 mg can be most conveniently used as small tablets as described in Example 6. Dosing. Larger compounds in unit M are most conveniently included in gel formulations that can accommodate higher unit doses of drugs. 44 (Please read the notes on the back before filling out this page) This paper size applies to Chinese National Standards (CNS) Α4 specifications (210X297 mm) 1222882 A7B7 V. Description of the invention (42) (Please read the precautions on the back before filling out this page) Table 2: Can be used to produce emulsification, mucosal adhesion, and improve adhesion Examples of compound types and pharmaceuticals. For convenience, they are labeled as primary (1 °) or secondary (2 °) emulsifiers. Multiple chemical agents can be used alone or in combination to fulfill their role as primary or secondary emulsifiers. Compound category / example preferred amount% w / w Surface charge (known) Regulatory nuclear preparation Note that gum arabic negative M and positively charged gels such as gelatin form a viscous condensation product alcohol cetylstearyl alcohol 1-20 F, M Secondary emulsifier stearyl alcohol 1-15 secondary emulsifier anionic emulsifying wax M primary self-emulsifier cellulose, propyl 5-35 G, F, M, R secondary emulsifier, stabilizer, tackifier Diethanolamine (DEA) 1-10 M, F, R one-time self-emulsifier gelatin 40-70 positive F, M gelling agent monoolein glycerol purpose 1-30 g, f, r one-time self-emulsifier, solubilizer 1 Glyceryl stearate 2-20 G, M, F, R Primary self-emulsifier, solubilizer, recording agent: lubricant lubricant lecithin 2-15 G, M, F, R Secondary emulsifier medium chain triglyceride Class M0 G, R secondary emulsifier, solvent 曱 cellulose 1-5 G, M, F, R secondary emulsifier, tackifier nonionic emulsifying wax 5-20 M, R primary emulsifier, tackifier Agent Polosama 2-10 M, F, R Secondary emulsifier, Tackifier Polydextrose Negative Tackifier Polyethoxylated Sesame Oil MO M, F, R One-time self-milk Agent, solubilizer, stabilizer Polyoxyethylene alkyl ethers 10-20 M, R self-emulsifier, solubilizer polyoxyethyl ether (Marker) 1-15 M, R self-emulsifier, solubilizer, Wetting agent polyoxyethylene fatty acid esters (Polysobe) 0.5-10 G, M, F, R One-time self-emulsifier, solubilizer polyoxyethylene ethyl stearate 0.5-10 M, F, R secondary emulsification Agent, solubilizer pregelatinized starch 1-20 negative g, f, r coagulate with gelatin, tackifier propylene glycol alginate 1-5 G, M, F, R secondary emulsifier, tackifier sodium lauryl sulfate 0.5-2.5 G, M, F, R one-time self-emulsifier polysorbate (polysorbate fatty acid ester) 0.1-15 food, M, F, R one-time self-emulsifier, tackifier starch 2-15 Negative G, M, F, R Tackifier, pastille diluent, dispersant Trisodium citrate 0.3-4 G, M, F, R Secondary emulsifier, pH modifier, release agent Applicable to this paper size China National Standard (CNS) A4 Specification (210X297 mm) -45-1222882

Μ-Important points Single chapter F-FDA Inactive Ingredients Guideline Acceptable R-Medicated parentheses, issued in the UK or Europe G- Usually considered safe TM11 Medicinal cannabisϋ Under pure glass as a strain 3 Week; thus maintaining the plant in a medicinal cannabis plant line from the germinated seed to 25t: ± 15t in the growth of vegetative state for 3 weeks under 24 hours light. By 12 hours of daily exposure to experience 8_9 weeks to induce flowering. No sanitary pesticides, herbicides, pesticides or fumigants were used. Phases are grown organically to control pests biologically. The main steps from seed to obtaining dried medicinal cannabis are summarized as follows: Obtaining seeds Germination in the UK (G-Pharm) seeds 1 Selection of cannabinoid content and degree of flute strength Mother plant

I Plugged and set roots on the peat plunger 14-21 days 25 C ’24 hours a day 1 After cutting, the cuttings were potted in 5 litres of compost per pot 1 Established young plants

3 weeks, 24 hours each, 25 ° C i Remove lower branches at the end of 3 weeks

1222882 A7 B7 V. Description of the invention (44) Used to generate a new generation of plugs 1 Induced flowering pots are moved to a length of 12 hours per day to induce flowering 1 Flowering and maturity at 25 ° C 8-9 weeks 1 Harvest 1 90% of flowers Leaf aging

I Dry under light conditions syringe. Covered TLC developing tank Hot hair dryer Silicone G TLC board (SIL N-HR / UV254), 200 micron thick layer on polyester support with fluorescent indicator. Developer immersion tank. Mobile phase 0% petroleum ether 60: 80/20% ether. Developer 0.1% w / v water-based fast blue B (100 mg in 100 ml of deionized 47 (please read the precautions on the back before filling this page) This paper size applies to China National Standard (CNS) A4 (210X297 mm) 1222882 A7 B7 V. Description of the invention (45 water). Another method is scanning under UV light 254 and 365 nanometers. B) Preparation of samples (please read the precautions on the back before filling this page) i) about 200 herbal raw materials耄 Grains of dried and dried marijuana were weighed and replaced in 10 ml volumetric flasks. The solvent was extracted with methanol: chloroform (9: 1) and adjusted to a constant volume. The extract was treated with ultrasound for 15 minutes. The supernatant was decanted and used directly for chromatography. ii) Herbal extracts Weigh approximately 50 mg of the extract into a 25 ml volumetric flask. Use ㈣ to adjust to constant volume. Dissolve vigorously and use directly for chromatography. C) Standards, 0.1 mg / ml Δ-9-THC in methanol. 0.1 mg / ml CBD in methanol. The standard solution is stored at -2 (rc, used for up to 12 months after initial preparation. .4 ^-d) test solution and method. The application points are separated by at least 10 亳. i) 5 microliters of herbal extract or 1 microliter of herbal extract solution as needed, ii) 10 microliters of 0.1 mg / ml △ j-THC in methanol standard solution, ni) 10 microliters of 0.1 mg / ml The TLC plate was eluted with CBD in methanol standard solution through a distance of 8 cm, and then the plate was removed. The solvent was allowed to evaporate from the plate and then the elution was repeated twice (dual development). The plate was briefly immersed in the rapid blue B reagent until the characteristics of cannabinoids began to develop.

1222882 A7 B7 5. Description of the invention (46) Repeated sign / orange. Remove the plate and allow the plate to dry in the dark under ambient conditions. Use a digital scanner (preferred option) to reproduce the image, or mark the location and color of the point on the tracer paper to record the result permanently. THC, THCA, CBD, CBDA and CBN verification analysis by HPLC a) Materials and methods Equipment HP 1100 HPLC has a diode array detector and automatic sampler. The equipment is set up and operated in accordance with the standard operating procedures (SOPlab037) in the factory. HPLC column Discovery C8 5 micron, 15x0.46 cm plus gold Kingsorb ODS2 front column 5 micron 3x0.46 cm. Mobile phase acetonitrile: methanol: 0.25% aqueous acetic acid (16: 7: 6 volume ratio) column operating temperature 25 ° C flow rate 1.0 ml / min injection volume 10 microliters running time 25 minutes detection of natural and acidic cannabis Phenol 2 20 nm (bandwidth 16 nm) Reference wavelength 400 nm / bandwidth 16 nm crack 4 nm acidic cannabinoids routinely 3 10 nm (bandwidth 16 nm) For qualitative verification and identification purposes only . Data capture HP Chemistation A7.01 board software b) Sample preparation Approximately 40 mg of cannabis-based drug extract was dissolved in 25 ml of methanol. This solution was diluted 1 to 10 in methanol. The diluent is used for chromatography. 49 (Please read the precautions on the back before filling this page) This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 B7 V. Description of the invention (47) Contained in the pump action under the tongue spray The unit's 0.5 ml filling solution was sampled using a glass burette. The solution was diluted in a 25 ml flask and adjusted to the mark position with methanol. 200 microliters of this solution was diluted with 800 microliters of methanol. Herbal or resin samples were taken by sampling 100 mg and treated with 5 or 10 ml of methanol / chloroform (9/1 w / v). The dispersion was treated with ultrasound in a sealed tube for 10 minutes, allowed to cool, centrifuged in its entirety, diluted with methanol as appropriate, and then chromatographed. c) Standards This method uses external standardization. THC, CBD and CBN standby standards are prepared in methanol or ethanol diluent to make the final working standard accurate to 0.1 mg / ml. The working standard is stored at -20 ° C and can be used for up to 12 months after initial preparation. The injection of each standard was repeated three times before the test solution was injected. Standards were repeatedly injected at appropriate intervals during the test solution treatment. In the absence of reliable CBDA and THCA standards, these compounds were analyzed using CBD and THC standard response factors, respectively. The washing sequence was measured as CBD, CBDA, CBN, THC and THCA. Other cannabinoids are identified and tested using this standard test as needed. d) Test solution The dilute test solution is adjusted to quantification in methanol and contains the analyte in a linear working range of 0.02-0.2 mg / ml. e) Chromatographic acceptance criteria: The following acceptance criteria were applied to the results of each sequence, because it was found to be 50 (please read the notes on the back before filling out this page) This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 Mm) 1222882

48 Obtained the appropriate resolution of Wang's knife analytes (including the two most eluted analytes, CBD and CBDA) 0 The residence time window of each knife analyte: CBD 5_4-5.9 minutes CBN 7. · 9- 8.7 minutes THC 9.6-10.6 minutes ϋ) Spike shape (based on the symmetry factor of the BP method) CBD < 1.30 CBN < 1.25 THC < 1.35 in) Mao exhibited a variety of standard method modifications to process samples containing spikes with late elution impurities, For example, method CBD2A extends the running time to 50 minutes. All solutions must be clarified by centrifugation before being transferred to the autosampler vial, sealed with a Teflon face septum seal and a cap. iv) The front column is of critical importance to the quality of the tomography and must be replaced when the back pressure rises above Bar and / or the acceptance criteria for dwell time and temperature exceeds the prescribed limits. f) Data processing 'Cannabis species can be subdivided into neutral and acidic cannabis species, and their qualitative analysis can be performed using the DAD dual wavelength mode. Acidic cannabinoids have strong absorption in the 220 nm-3 10 nm region. Neutral plane τ Cannabinol is strongly absorbed only in the 220 nm region. Routinely use only the recorded data of 2 2 0 μm and 5 for Dingdan Bacheng -51-1222882 A7 ____B7 _ 5. Description of the invention (49) DAD can also be used to scan the spectrum of purple peaks of each peak Stored in spectral library for identification purposes. (Please read the precautions on the back before filling out this page.) The quantitative data processing uses HP Chemstation batch processing software. a) Sample chromatograms The chromatograms of HPLC samples are provided below. They are THC and CBD herbal extracts, respectively. CBME CBD: J 4 c 9- 〇ϊ CBD CBME example chromatogram (AC881) 0- 〇V., 'Ί -1' 〇 «9 7; 3 Will tS heart 20 CBME THC: BA01 A. S ^ < 20.t * e * MM〇〇ii * ^ > AMpLCDA.t, 〇ATAV100〇jevCe〇Me21jjf THC CBME example chromatogram (AC882)

Example 17 The preparation of herbal extracts is shown in a flow chart. The procedure for making extracts from high THC and high CBD Qimo variants is as follows: 52 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 V. Description of the invention (50) Medical cannabis (high THC or high CBD) 1 cut into mainly 2 to 3 mm in length i to 100 to 15 (TC heated for a sufficient time to decarboxylate cannabinoid acid form to make neutral cannabis 1 Extraction of liquid carbon dioxide of a specified volume for 6 to 8 hours by removing carbon monoxide under reduced pressure and recovering the crude extract "wintering"-dissolving the ingenious extract in ethanol (European Pharmacopoeia) followed by rapid cooling (-20 C / 48 hours) to precipitate Undesirable wax / I Remove undesired waxy material by cold filtration Evaporate ethanol from the filtrate by evaporation under reduced pressure f Example 18 High THC content cannabis in a greenhouse at an average temperature of 21 + 2 It is relatively wet 50-60 % Growth. &Amp; Obtained herbs in the dark at room temperature and relative: two and 40-50% dry. When dry, the leaves and flower heads are removed from the stem, and the dried raw materials are called "medicinal cannabis." Hemp is ground into coarse (Particles can pass through a 3 mm sieve) Fill the supercritical fluid extractor chamber. The packing density is 0, pressure_bar $ ^ oxygen, carbon at 35X: temperature passes through biological matter. Supercritical extraction is performed for 4 hours. The pressure was gradually decompressed and the extract was recovered in the collection container. The resulting green-brown oily resin-containing extract was further purified. Dissolved in ethanol step ⑽) Placed at -2 (TC temperature 24 hours' sediment (from fat-soluble The bad substance group is removed by filtering out of the solution. The solvent is removed from the rotary evaporator at a low pressure. (Please read the precautions on the back before filling out this page.) •, η— This paper size applies to China National Standard (CNS) A4 specification (210X297 public ^ 1222882 A7 B7 5. Except for the description of the invention (si). The obtained extract is a soft extract containing about 60% THC and about 6% of other cannabinols, of which 1-2% It is cannabidiol and the rest are minor cannabinoids containing cannabinol. Quantitative results are based on dry medicinal weight of cannabis = 9% w / w. Chimo variants with a high content of CBD are treated in a similar manner to obtain approximately 60% CBD With up to 4% tetrahydrocannabinol, others Extracts with a total amount of cannabinol of less than 60%. The extracts were obtained using the aforementioned general method using THCV and CBDV Chimo variants. Those skilled in the art know that other temperature and pressure combinations (+10 t to 35 ° C and 60- 600 bar) and extracts are produced under supercritical and subcritical conditions. Example 19 Street cannabis (marijuana) grown in the United States and the Caribbean countries typically contains a high percentage of THC; European cannabis (often referred to as "Morgen" cannabis) contains approximately the same amount of THC and CBD. This illustrates the conflict between some reports of clinical studies of the efficacy of cannabis. The applicant seeks to produce a specific ratio of cannabinoids in two ways; through the use of a mixture with a specific extract, and through the use of extracts from a single Kimo variant which produces the appropriate ratio of cannabinoids. The Chimo variant, whose cannabinoid is mainly expressed as a compound, is used to prepare the formulation of the present invention, but the teachings of this case can also be applied to the synthetic production of cannabinoid or the cannabinoid obtained from purified cannabis. Some Qimo variants exhibit a ratio of about 50:50 THCV / CBDV. It is therefore convenient to use a single plant extract to provide a hemp-like ratio. When the plant line was grown by plugging, the genotype was fixed and the cannabis-like ratio was uncertain. The total yield can be changed, but the reason is to produce a specific amount of cannabinoids. 54 (Please read the precautions on the back before filling out this page.) This paper size applies to China National Standard (CNS) A4 (210X297 mm). ) 1222882 A7 B7 V. Description of the invention (52) Material consumption. The formula especially suitable for the treatment of multiple sclerosis is as follows: CBME extract of Qimo variant G10 provides 0.208 5b 5c THCV 0.1 2.5 10 parts CBDV 0.1 2.5 10 parts spray-dried lactose 60 60 50 parts dextrose 37.7 21.5 16.5 Parts of egg filling 1 10 10 parts α_ fertility hope 0.1 2.5 2.5 parts of magnesium stearate 1 1 1 parts (please read the precautions on the back before filling this page) CBME-G10 extract is dissolved in 5 parts of ethanol. To make the other ingredients into a mass. The mass is sieved under pressure and the granules are dried at low temperature. When dry, the granules are sprinkled with magnesium stearate powder and pressurized at 1.5 Newtons to produce lozenges suitable for sublingual administration in patients with multiple sclerosis, chordal injuries, peripheral neuropathy or other neurogenic pain. Example 20 A multi-layered dosage form was developed for the manufacture of cannabidiol previously used in THC. In this example, THC obtained from synthetic or natural sources is contained in the core. CBDs derived from natural sources such as cannabis kimo variant extracts or CBDs from other synthetic materials are present in the outer coating, which is first dissolved followed by THC dissolution. A double-layered ingot was prepared from the following ingredients. Inner core: CBME-G1 provides THC 2 parts direct compression lactose 66.9 parts pregelatinized starch 30 parts oc-tocopherol 0.1 part magnesium stearate 1 part 55 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) ) 1222882 A7 B7 5. Description of the invention (53) CBME is dissolved in a sufficient amount of ethanol, and the whole is sprayed on other dry ingredients. Allow the powder to dry at room temperature and mix thoroughly. Add magnesium stearate and tablet to a 6 Newton hardness. The core is conveniently compressed using a spindle press with a 7mm biconvex die. In the BP type disintegration device test, the core disintegration time is 5-10 minutes. Outer layer: The outer layer of the tablet is prepared from the following ingredients: CBME-G5 8 parts glyceryl monostearate 5 parts egg filling 5 parts direct compression lactose 55 parts pregelatinized starch 26.7 parts alpha-fertility 0.2 parts mint oil 0.1 part A sufficient amount of ethanol BP was used to dissolve the CBME extract and then spray onto other dry ingredients. The ethanol was allowed to vaporize at room temperature. The dry granules were thoroughly mixed and pelletized, and a half feed was sent to a 9 mm die. This feed was lightly compressed (0.25 Newtons), one ingot core prepared as described above was added to each die, and the remaining ingot particles were added to the die. The tablets were pressed to a 1.5 Newton hardness. The lozenges thus produced have a soft outer coating that is compressed to be hard enough to withstand limited handling and individually sealed in a blister pack to reduce brittleness. When the lozenge is placed under the tongue, the soft outer layer quickly disintegrates to form a microgelled mass to obtain CBD. This coating has a disintegration time of 1-4 minutes in the PB-type disintegration device test. Harder cores containing THC are then dissolved and THC is obtained after CBD and provided to the sublingual or buccal mucosa. Using double-layer ingots in this way, 56 (Please read the notes on the back before filling this page) This paper size applies to China National Standard (CNS) A4 specifications (210X297 mm) 1222882 A7 B7 V. Description of the invention (54) Yes Get the best presentation order for cannabinoids. The pre-absorbed CBD has antioxidant activity in test tubes and in vivo tests, which is conducive to improving the stability of THC and assisting the absorption of THC. The CBD component used to provide the THC component extract contains a relatively small amount of CBD. CBD is used as an antioxidant, so it contains extra fertility as a chemical antioxidant. The bond thus made can be used to treat multiple sclerosis and other neurogenic pain. The lozenge mixture is also suitable for treating rheumatoid arthritis and other inflammatory bowel diseases when it is compressed to 6 Newton hardness and administered as an oral preparation intended for swallowing. Unexpectedly, although cannabis has been reported to stimulate appetite, direct experiments have shown that high CBD extracts reduce food intake and weight gain in mice. Therefore, high CBD formulations can be used as a way to reduce human appetite. Example 21 A specific variant of Kimo (labeled G9) produces two major cannabis-like THCV: THC ratios of 85:15. This Kimo variant produces a relatively small amount

CBD, which results in an extremely high THC: CBD ratio. THCV achieves a faster analgesic effect than THC, and hangover may be reduced. Therefore, the medicament prepared from this extract is suitable for the treatment of opiate-resistant pain, and it is desirable to start the action quickly here. The sublingual spray formulation has the following formulation. The CBME-G9 extract provides THCV 85 parts THC 15 parts CMO RH40 300 parts α-tocopherol 1 part ethanol BP Manufacture 1,000 parts The ingredients are dissolved in ethanol and mixed into a glass vial at a rate of 10 liters, using 57 ( Please read the notes on the back before filling this page.) This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 B7 V. Description of the invention (55) Sealed by the pump operation spray dispersing button. Each milliliter of product contains 100 mg of cannabinoids. Each pump delivers 100 microliters of a fine spray. The spray is directed to the sublingual mucosal area. This preparation is used as part of the treatment of patients with migraine, cancer pain and multiple sclerosis. Example 22 The formula described in the previous example was made by replacing CBME-G5 (high CBD). This spray is used to prime the patient and give a dose of CBD 5-10 minutes before administering the high THC / THCV formula. Proprietary two-compartment / dual pressure buttons are available, and the compound package contains the solutions described in this and previous examples. Conveniently, there are two sublingual solutions in one package so that the patient can adjust the dosage of any one of the components to obtain the desired optimal effect. The antioxidant effect of CBD in a test tube is stored at 5 ± 3 ° C and verified by the following analysis. Data are reported as a percentage of the initial analytical value. Table 5: Qualitative data of high THC, high CBD and equilibrium ratio CBD / THC, pump action spray (PAS), and sublingual tablets. The analytical analysis value of the formula after a period of 3 months (range) 6 months (range) PAS THC CBD THC CBD High THC 98.2 95.6 (95.6-100.4) (93.7-98.5) High CBD 100.6 101.0 (99.7-101.6) ( 98.3-103.6) Equilibrium ratio 99.5 101.2 100.4 104.5 THC: CBD (98.3-101.5) (100.3-102.0) (99.3-102.8) (193.5-106.5) 58 (Please read the precautions on the back before filling this page) The paper size Applicable to China National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 B7 V. Description of invention (56)

Sublingual tablets are stored at 5 ° C. High THC 98.4 (2 mg). High CBD 99.0 (2 mg). Equilibrium ratio 95.5 99.0. It is clear from the above table that the CBD of the present invention has good stability, while THC is less stable. Formulations containing CBD and THC at a concentration of therapeutic interest are clearly protective and can improve the stability of spray and lozenge products with a balanced ratio. The above examples illustrate the teachings of the present invention. It will be apparent to those skilled in the art that various components derived from different formulations can also be adjusted to produce a wide range of formulations. These formulations are suitable for treating a range of therapeutic indications, and each element can be obtained from any of the foregoing examples to produce a specific formulation that has a predetermined onset rate of action and duration of action within said limits. Example 23 It is known that cannabinoids can be used to treat inflammatory bowel disease. However, the amount of cannabinoids reaches the lower large intestine (distal ileum and colon). Ritual preparations are suitable for topical application to the inflamed large intestine. The formula below is based on a foaming raccoon formulation that provides a wide range of cannabinoid combinations for topical use. GBME-G1 Provide THC 4mg CBME-G5 Provide CBD 20mg Docusate Sodium 100mg Monostearate 2.5g Carboxymethyl cellulose 250mg Water 250ml 59 (Please read the precautions on the back first (Fill in this page again.) This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 1222882 A7 ___ B7 V. Description of the invention (57) The CBME extract is dissolved in the ingredients and mixed in the order previously indicated. Each 50¾ liter serving is filled in a compressible plastic container, which is equipped with a 150ml sacral nozzle with a ball at the end. Prior to use, the container was shaken vigorously to produce foam. Foam is injected through the nozzle, and the amount of foam produced is typically feasible to enter the lower intestine 1-2 meters in length. Foams are compressible, and the relatively incompressible coelenterate minimizes patient discomfort. The treatment can be combined with a systemic or enteric dosage form to administer steroids to treat inflammatory bowel disease. Example 24 When the product described in Example 10 was placed in the superior popliteal fossa, the components were released into the buccal mucosa, but saliva in the entrance cavity was also released. Coating the convex surface of the gel with a substance that is more insoluble than the substance of the gel itself will reduce the amount of active ingredients lost in saliva, thereby increasing the contact concentration with the buccal mucosa. The formula described in Example 丨 can be further modified to provide a gel, in which the coating on the convex surface of the gel (proximal I surface or inward surface) forms an integral part of the product. This additional layer delays the dissolution of the gel and is called a water-insoluble layer (WIL) for convenience. The water-insoluble layer is a thermosetting gel, which is first mixed in a mold at a temperature of 50-8 (rc temperature, and then the example ⑺ or "the formula is formulated in the manner and order described in this example while hot. When When the water-insoluble layer is still in the melt state, mixing the melted shellfish can spread the water-insoluble layer around the concave mold, and as a result, a layer is formed on the convex side of the gel after the mold I was made. The distal end of the gel is partially dissolved and the water-insoluble layer is not dissolved. I The water-insoluble layer is made of the following composition, where the gum arabic concentration of Example 11 is increased to obtain a more rigid gel structure component. CNS) A4 size (× 297mm)--

----------------------fee! -·· (Please read the notes on the back before filling this page) • Order — 1222882 A7 B7 Description of the Invention (58) Glyceryl monooleate 5 parts Soy lecithin 5 parts Gum arabic 30 parts Tetrahydrocannabis 10 parts α -Tocopherol 0.1 parts xylitol 3 parts glycerin 3 parts pure water 100 parts Each component was mixed as described in Example 11 and heated to dissolve. The whole batch is mixed in a mold or die-cast into flakes. The water-insoluble layer of the formula is similar to the layer described in Example 11, and as a result, the interface is slightly mixed, and the ingredients are bonded to form a cohesive product. The types and proportions of cannabinol described in other examples can also be introduced into the multilayer products described in this example. Example 25 A water-insoluble layer can also be formed on a gel by, for example, spraying 5% ethyl cellulose on an inner surface of a mold and then introducing the first component described in Example 10. The alcohol solution is sprayed through a cover that protects the mold intended to have the surface of the adhesive layer of the starting and sealing film. The solvent was allowed to vaporize and then the gel described in Example 10 was introduced. This procedure has the added benefit of reducing the bioburden on the inside of the mold if required. When the molding composition is introduced into the mold, it strongly adheres to ethyl cellulose and forms a water-insoluble layer. The drug is formed on a flat surface by casting a multilayer material, and a 5% ethyllin solution is sprayed on the surface. After the solvent was vaporized, the composite layer described in Example 10 was formed thereon. ^ Ruler Tengzan)--(Please read the notes on the back before filling this page), tr-1222882 A7 B7 V. Description of the invention (59) References

Adams M.D. et al (1977) A Cannabinoid with Cardiovascular Activity but no Overt Behavioural Effects Experientia, 33, 1204-1205

Burstein S. and Raz A- (1972)

Inhibition of prostaglandin E2 biosynthesis by Dl-tetrahydrocannabinol. Prostaglandins 2: 369-375 ·

Ed; Brown D.T, 207 Cannabis' The Genus Cannabisr

Carlini E-A., Leiter J.R., Tannhauser M. and Berardi A.C. (1973) Cannabidiol and Cannabis sativa Extract

Protect Mice and Rats Against Convulsive Agents J. Pham. Pharmacol 25, 664-665

Davis KH Jr., McDaniel IA Jr., et al Some Smoking Characteristics of Marijuana Cigarettes The Cannabinoids: Chemicalr Pharmacologic and Therapeutic Aspects 62 This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 1222882 A7 _____B7 V. Invention Explanation (60)

Academic Press, Inc. (1984)

De Meijer E.P.M. and Keizer L.C.P. (1996)

Patterns of diversity in Cannabis. Genetic Resources and Crop Evolution, 43 ^ 41-52

Guy G W, Whittle B A and Grey MJ

Dose dispensing Apparatus GB Pat Application 25809.5, Oct 20, 2000

Guy G W, Whittle B A and Grey M J

Secure dispensing of materials GB Patent Application 25811.1, Oct 20, 2000

Hampson A.J., Grimaldi M., Axelrod J. and Wink D. (1998)

Cannabidiol and (-) 9-Tetrahydrocannabinol are

Neuroprotective Antioxidants

Proc. Nat. Acad. Sci. 95, 8268-8273

Hardy et al

Respiratory Medicine (1993) 87: 461-465

House of Lords Science and Technology Sub Committee report

The Development of Prescription Cannabis-Based Medicines (Jan 2001)

In-house Report GPA 002/000159 CBD Primary Screening Program (2000)

Iversen L-L.

The Science of Marijuana / Oxford University Press / 48-49 (2000)

Mechoulam R ed. ,,. This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 63 (Please read the precautions on the back before filling out this page) • Order — 1222882 A7 _____B7_V. Description of the invention (Μ) Cannabinoids as Therapeutic Agents, CRC Press, Boca Raton, FL, New York (1976) Merck Index, 12th Edition, (1996) # 1792 Merck's Manual (1899), Part 1, pg 26. Fate D · US Patent Application Number 08/919317, 28 August 1997 Pertwee RG, (1998) Advances in Cannabinoid Receptor Pharmacology in Cannabis The Genus Cannabis (Ed Brown DT,) Harwood Publishers, 125-174 Petro DJ (1980} Marijuana as a Therapeutic Agent for Muscle Spasm or Spasticity Psychosomatics 21 (1), 81-85 Price MAP, and Notcutt WG Cannabis in Pain Relief In Cannabis: The Genus Cannabis (Ed Brown DT) Harwood Publishers, 223-246 Raman A. The Cannabis Plant: Cultivation and Processing for Use In Cannabis: the genus Cannabis, 29— 54, Ed Brown DT Ram and Sett (1982) Zeitschrift fur pflanzenphysiologie, 107 (1), 8 5-89 Samuelsson G Drugs of Natural Origin 15S-160Swedish Pharmaceutical (Please read the precautions on the back before filling out this page) Order — This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 64 1222882 A7 B7 Description of the invention (62)

Press, Stockholm, Sweden, Smiley KA ·, Karber R. and Turkanis SA (1976) Effect of Cannabinoids on the Perfussed Rat Heart Res · Comm · Chem · Pathol. Pharmacol, 14, 659 ^ 673 Tashkin DP, Shapiro BJ, and Frank IM Acute pulmonary and physiological effects of smoked marijuana and oral delta-9-THC in healthy young men N Eng J Med, 289, 336-341 Touitou E US Patent 5,540,934 (July 30, 1996) Touitou E, Fabin B, Danny S and Almog S Transdermal Delivery of Tetrahydrocannabinol Engineering J. of Pharmaceutics (1988) 43: 9-15 Whittle B Ά and Guy GW Formulations for sublingual delivery GB Patent Application 103638.3, Feb 14r 2001 Zuardi AW. And Guimares FS (1991) Cannabidiol as an Anxiolytic and Antipsychotic in Cannabis: The Medicine Plant McFarland & Co, London: 133-141 (Please read the notes on the back before filling this page)

, T This paper size applies to Chinese National Standard (™ s) A4 specification (210X297)

Claims (1)

1222882_Announcement AfiBSss ΨPlease find the profit scope No. 91102626 Patent Application Application Patent Range Amendment Date of revision 5 · 93 · 5 # 1 · A pharmaceutical formula for the administration of lipophilic drugs through the surface of the mucosa, which contains one or more lipophiles Drugs and one or more self-emulsifiers, wherein when hydrated, the formulation forms a lipophilic drug-containing emulsion that can adhere to the surface of the mucosa and allows the drug to be released in a controlled manner. 2 · If the scope of patent application is the first! The formulation of this item is not a propellant-driven aerosol or propellant-driven liquid spray formulation. 3. The formula as described in Lifanfan or Item 2, which contains—or multiple tackifiers. 4. The formulation in item 3 of the patent scope, wherein the tackifier is a block copolymer of oxyethylene and oxypropylene. 5. The formulation according to item 3 of the patent application range, wherein the thickener is not a non-ionic surfactant. Printed by the Intellectual Property Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs ^ 6. If the formula in the scope of patent application No. 5 contains one or more tackifiers, a gel is formed when the field is hydrated, with a positive surface charge, and one or more additives are added. Adhesives form a gel with a negative surface charge when hydrated. For example, the formulation of item 6 of the "Monthly Patent Scope" includes-or more mold-increasing agents which form a gel with a positive surface charge when S is hydrated, the viscosity-increasing agent is gelatin or sugar gelatin; and one or more viscosity-increasing agents It forms a gel with a negative surface charge when hydrated. The tackifier is starch, pregelatinized starch, gum arabic or polydextrose. The formulation of the third item of the patent claim states that one or more of the tackifiers are solubilized by the peak action existing in saliva. 66 ㈣ ((: Ν5) Α: ϋ ^ 22882 'Scope of patent application 9. If the oldest formula in the patent scope is requested, it is a solid dosage form. The formulation of Guarulone's patent application No. 9 is a gel, a bonding agent or a capsule. 】】 · For example, the formula in the scope of patent application No. 9 is a coagulation type for administering lipophilic drugs through the sublingual or mucosa-like or both, where when contacted with saliva, coagulation or gel spray The agent forms a lipophilic drug emulsion and adheres to the sublingual or buccal mucosa, or both. 12. The formula of item 9 in the scope of the patent of Shenyang, which is in the form of a sharp formulation for the administration of lipophilic drugs through the sublingual or buccal mucosa, or both, wherein the contact agent completely disintegrates when it comes into contact with saliva. A lipophilic drug-containing emulsion is formed which adheres to the sublingual or buccal mucosa or both in a reversible manner. 13. If the formula of patent application range 9 or _, the total amount of thickener included in the formula is higher than 60% w / w of the formula. k The formula according to the scope of patent application, wherein the self-emulsifier is present in an amount of at least 5% w / w. 15. The formulation according to item 14 of the patent application scope, wherein the self-emulsifier is present in an amount of at least 10/0 w / w. K is the formula in the scope of patent application, which contains one or more solvents. M. As for the formula in the patent application scope of domain 2, it contains one or more midwifery agents. Ling 18. The formulation according to item Π of the scope of patent application, wherein the co-solvent is an office solvent. Zinc I9 · If the formula in the scope of patent application is No. 18, where the solubilizer is polyoxyethylene ^^ IB3 Continued on the back & notes before filling out this page) • Pack two 'll · 67 1222882 Six A8 B8 C8 _ · ______ D8. Patent application ethyl onion sesame oil derivative. 20. The formulation according to item 19 of the scope of patent application, wherein the polyoxyethylene castor / bamboo is crnophor. 21. The formulation according to item 20 of the scope of patent application, wherein the polyoxyethylated castor oil derivative is Camofo RH40. 22. The formulation according to item 6 of the patent application, which is a gel spray. 23. The formulation according to item 22 of the patent application, which is in the form of a gel spray for administering lipophilic drugs through the sublingual or buccal mucosa, or both, wherein the gel or gel spray forms upon contact with saliva A lipophilic drug emulsion that adheres to the sublingual or buccal mucosa, or both. 24. If the formula in the scope of patent application No. 16 contains one or more viscosifiers, the total amount of viscosifiers included in the formula is at least 10 / 〇w / w 〇25. If the patent is applied for The formula of the range item 16, wherein the self-emulsifier is present in an amount of at least 2% w / w. 26. The formulation according to item 25 of the application, wherein the self-emulsifier is present in an amount of at least 5% w / w. 27. The formulation according to item 丨 of the patent application scope, which comprises one or more self-emulsifiers selected from the group consisting of monoolein, glyceryl monostearate, and self-emulsifying grade monoglyceryl stearate. 8. The formula according to the scope of application for patent, wherein the lipophilic drug is a marijuana stroke extract. For example, the formula of claim 1, wherein the lipophilic drug contains one or more natural or synthetic cannabinoids. And --------------- ^ ^! Ϊ́: ΐί- (CNS) A ··! (2.1ϋ ^ 297) — ·· 装 -------- Order- ------- (Please fill in this page with Mtt's notes before filling in this page) 蛵 ^ 部 智 #? ^ Industrial Bureau staff elimination cooperation >: 1 Initiation 68 • If you apply for patent scope item 29 Formulation 'wherein the lipophilic drug contains tetrahydrocannabinol, Δ9-tetrahydrocannabinol, A9-tetrahydrocannabinol analog, cannabidiol, cannabidiol propyl analog, cannabinol, cannabis chromogen Alkenes, cannabinol dipropyl analogs, and cannabigeroi or any mixtures thereof. 31. A pharmaceutical formula for administering lipophilic drugs via a mucosal surface, the formula comprising one or more lipophilic drugs and one or more self-emulsifiers, wherein when hydrated, the formula forms a lipophilic drug-containing emulsion that can adhere to The surface of the mucosa and allows controlled release of the drug, wherein the lipophilic drug is one or more extracts obtained from a cannabis plant. 32. A pharmaceutical formulation for administering lipophilic drugs via a mucosal surface, the formulation comprising one or more lipophilic drugs and one or more self-emulsifiers, wherein when hydrated, the formulation forms a lipophilic drug-containing emulsion that can adhere to Mucosal surface and allows controlled release of the drug, wherein the lipophilic drug comprises a combination of two or more natural or synthetic cannabinoids. 33. The formulation according to item 32 of the patent application scope, wherein the lipophilic drug comprises two or more selected from tetrahydrocannabinol, A9_tetrahydrocannabinol, A9 · tetrahydrocannabinol propyl analogue, cannabis Any combination of diphenol, cannabidiol propyl analog, cannabinol, cannabinol, cannabinol analog, and cannabis such as cannabis. 34 · —A pharmaceutical formula for administering lipophilic drugs through the mucosal surface, the formula comprising one or more lipophilic drugs, one or more solvents, one or more co-solvents, and one or more self-emulsifying agents, wherein when hydrated At the time, the formula formed an emulsion containing lipophilic drugs, which can adhere to the surface of the mucosa and allow 69 1222882 six 3 ---- 1-^^ Ministry of Economic Affairs Intellectual Property Bureau staff consumer goods cooperatives to print; ^ A8 B8 C8 D8 Application The patent scope releases the drug in a controlled manner, which is characterized in that the total amount of solvent and co-solvent in the formula is greater than 55% w / w of the formula. 35. The formulation of item 34 in the scope of patent application, wherein the total amount of the solvent plus co-solvent in the formulation is higher than 65% w / w of the formulation. 36. The formula as claimed in claim 35, wherein the total amount of the solvent plus co-solvent in the formula is higher than 70% w / w of the formula. 37. The formulation of claim 36, wherein the total amount of the solvent plus co-solvent in the formulation is higher than 75% w / w of the formulation. 38. The formulation of item 37 in the scope of patent application, wherein the total amount of the solvent plus the co-solvent in the formulation is higher than 85% w / w of the formulation. 39. The formulation according to item 35 of the scope of patent application, which comprises 80% to 95% w / w of solvent plus co-solvent. 40. The formulation according to any one of claims 34 to 39, wherein the solvent is a lower alkyl (CKC1) alcohol, and the co-solvent is propylene glycol, glycerin, macrogoh or polyoxyhydrogen. castor oil. 41. The formulation according to item 40 of the application, wherein the solvent is ethanol and the co-solvent is propylene glycol. 42. The formula as claimed in item 41 of the patent application, wherein the ratio of ethanol to propylene glycol present in the formula is 4: 1 to 1: 4. 43. The formulation according to item 42 of the application, wherein the ratio of ethanol to propylene glycol present in the formulation is about 1: 1. 44. The formulation according to item 40 of the application, wherein the solvent is ethanol and the co-solvent is polyoxyhydrogenated castor oil. 45 · If the formula of the scope of application for the item 44 of the patent, the co-solvent is Kemofo (please pay attention to the back of / 53 碛 before filling this page) Φ 70 1 (CNS> / V 丨 Specifications (2J0 1222882 8888 ABCD Employees of the Intellectual Property Office of the Ministry of Economic Affairs, cooperation and cooperation seals) 六 、 Applicable patent scope RH40TM 〇46. For the formula of patent scope item 44, where the oxygen The amount of wanseed sesame oil in the formula is 5% to 55% w / w of the polyoxyhydrogenated castor oil and ethanol present in the formula. 47. For example, the formula in the 46th area of the patent application, wherein the polyoxygen The amount of hydrogenated castor oil in the formula is 20% to 40% w / w of the total amount of polyoxygenated sesame oil plus ethanol present in the formula. 48. The formula according to item 47 of the patent application scope, wherein the polyoxygenated hydrogen The amount of castor oil in the formula is about 30% w / w of the total amount of polyoxygenated castor oil plus ethanol present in the formula. 49. If the formula for the scope of patent application No. 34, the presence of the self-emulsifier $ It is based on 1% w / w of the formula. 50. If the formula in the scope of patent application No. 34, its package Contains glyceryl monooleate as a self-emulsifier. 51. For example, the formula in the scope of patent application No. 34, wherein the lipophilic drug is one or more cannabis extracts. 52. In the formula, the scope of patent application No. 34, wherein the The lipophilic drug contains one or more natural or synthetic cannabinoids. 53. The formulation according to item 52 of the patent application, wherein the lipophilic drug contains tetrahydrocannabinol, Δ9-tetrahydrocannabinol, A9 · tetrahydrocannabinol Propyl analogs, cannabidiol, cannabidiol propyl analogs, cannabinol, cannabis color women, cannabis color propyl analogs, and cannabigerol or any mixture thereof. Marijuana-based medicinal formula, which contains cannabidiol (CBD) and the note on the back of K1. Then fill in this page ^ Page I ^! II 1 ί I 1 丁 III Lu 71 1222882 ABCD Intellectual Property Bureau, Ministry of Economic Affairs Employee Consumer Goods Cooperative Co., Ltd. < 6. Application for Patent Scope Cannabinol such as tetrahydrocannabinol (THC), or cannabinol such as hypotetrahydrocannabinol (THCV) and subcannabindiol (CBDV), etc. Pre-defined 55. For example, the medical formula of item 51 in the scope of patent application, which contains approximately two equal amounts of cannabis by weight: cannabis (CBD) and tetrahydrocannabis age (THC). 56. The medical formula of item 51 of the patent scope includes two types of cannabinol: cannabidiol (CBD) and tetrahydrocannabinol (THC), wherein the amount of THC present by weight is greater than the amount of CBD present by weight. 57. For example, the medical formula of item 51 of the patent application scope includes two types of cannabinol: cannabidiol (CBD) and tetrahydrocannabinol (THC), wherein the amount of CBD present by weight is greater than the amount of THC by weight Existing amount. 58. For example, the formula in the scope of patent application No. 57 wherein the weight ratio of CBD to THC is greater than 2.5: 1. 59. For example, the formulation of the 57th or 58th patent application range, wherein the weight ratio of CBD to THC is 99: 1 to 2.5: 1. 60. For example, the formulation of the 59th patent application, wherein the weight ratio of CBD to THC is about 20: 1 to about 2.5: 1. 61. For the formulation in the 57th patent application, the weight ratio of CBD to THC is about 19 ·· 1. 62. For example, the formulation of the scope of patent application No. 57 wherein the weight ratio of CBD to THC is in the range of about 5: 1 to about 3: 1. 63. For example, the formula in the 57th scope of the patent application is substantially free of cannabinols other than CBD and THC. 9 * t --------- IT --------- (¾ ^^ 纩 Notes on the back before filling this page) 72 1222882 Six A8 B8 C8 ^ ----- ^ _ Patent application range 64. The formula as claimed in item 63 of the patent application range does not substantially contain any other types of cannabinol in the cannabis species. 65. If the formulation of the scope of patent application No. 57, wherein the CBD and THC are in a substantially pure form. 66. A formulation according to item 57 of the application, which contains one or more other types of cannabinol. 67. The formulation according to item 66 of the application, wherein the one or more other types of cannabis are hypotetrahydrocannabinol (THCV) or hypocannabinol (CBDV) or both. 68. The formulation of any one of claims 57, 66, or 67, wherein the 申请 CBD and THC are derived from one or more stroke extracts of one or more cannabis plants, and the one or more extracts comprise the plant Of all natural cannabis. 69. If the formula of the scope of patent application is applied, the cannabis plant line is selected from wild cannabis (Cannabis sativa), Indian cannabis (Cannabis indica), gene interlaced, self-interlaced or hybrid. 70. For example, the formula for the scope of patent application No. 69, wherein the cannabis plant is wild cannabis, the Indian subspecies and is selected from the Indian variant and the kafiristanica variant. 71. The formulation according to item 68 of the patent application scope, which comprises extracts obtained from two or more different varieties of cannabis, wherein in the final formulation, the CBD content by weight is higher than the thc content. 72. The formula in item 68 of Patent 4, wherein the extract is prepared by supercritical or subcritical fluid extraction of dried cannabis plants.丨 丨 _Installation -------- Order --------- 0 (please fill in this page on the back of Mtt first!! * Matters and then fill out this page) Printed by the Ministry of Economic Affairs ^ Housing Bureau employee consumer cooperative. No 5.: ;; (CNS) A :! Secret 73 1222882 AS B8 C8 -----_; ___________ D8 VI. Application for Patent Scope 73 · — A method for preparing a medical formula based on hemp, the formula contains CBD and THC have a pre-defined weight ratio, and the method includes the following steps: a) providing one or more dried cannabis plants, the cbd and THC contents of which are known by weight; b) preparing the one or more cannabis Plant extracts; c) formulating the material from the extract prepared in step (b) with the pre-defined CBD to THC ratio; and. D) using a pharmaceutically acceptable carrier or excipient to step The product is formulated into a pharmaceutical formula. 74. As claimed in the method of patent scope item 73, wherein the step ⑻ extract is prepared using one or more of the following procedures: ⑴ dipping (ii) diafiltration (in) using a solvent such as eves alcohols, norfolk blue ( Norflurane) * HFA227 extraction (iv) subcritical or supercritical fluid extraction. Employees of the Intellectual Property Bureau of the Ministry of Economic Affairs, Xiaoxian Cooperative Association 75. If the method of applying for the scope of patents No. 73 or 74, before the extraction, the dried cannabis is heated to about 6 (rc to about 22 generations, the extract is present 76. The method according to item 75 of the patent application, wherein before extraction, the dried marijuana is heated to about the generation of the extract to the centipede. Deacidification of any acid form of cannabinoid. 77. If the scope of patent application is 73, it includes the use of supercritical or sub-sixth, patent application scope: critical carbon dioxide extraction of one or more cannabis plants. 78. Rushen 4 Patent & Method around item 73, wherein after using supercritical or subcritical fluid extraction, the extract is subjected to "wintering" and the pest is removed from the extract. Method, wherein the weight content of the CBD in the formula is higher than the weight content of THC. 80. The method of claim 73, wherein the pre-defined ratio of eBD to THC by weight is 99 ... 2.5: 1. 81. For example, the method of claiming the scope of patent 80, in which the pre-defined ratio of cBD to THC by weight is about 2 (^ j to about 2.5: j. 82. The method of scope of patent 73 Among them, the pre-defined ratio of cBD to THC by weight is about 19: i. 83. If the method of the scope of patent application is 73, the pre-defined ratio of CBD to THC by weight is about 5: work To 3: i. 84. If the method according to the scope of the patent application is 73, the formula contains approximately equal amounts of CBD and THC by weight. 85. If the method according to the scope of the patent application, 73 is in the formula, The content of THC by weight is higher than the content of CBD by weight. 86. If the method of the scope of patent application No. 673, the pre-defined ratio of CBD to THC by weight is 1: 5. 5. 87. For example, the method of applying for the scope of patent No. 73, in which the pre-defined ratio of CBD to THC by weight is about 丨: 39. 88. The method of applying for the scope of patent No. 73, wherein the CBD defines THC by weight in advance The ratio is about 丨: 2. -75-1222882 B8 C8 D8 Six classics ^ 部 智 #.? The staff of the property bureau eliminates cooperation ^ print ^ A please apply for the scope of the patent 89. If you apply for the 73rd method of the scope of the patent, the formula is formulated for nasal , Sublingual, buccal, topical, A mouth, transrectal, transvenous, intra-abdominal, muscular, subcutaneous, transdermal, intravaginal, intraurethral, by nebulizer, by inhalation of vapor or by direct installation in the bladder to deliver drugs . See the method in the scope of patent application No. 73, wherein the formula is formulated to deliver the CBD before the THC rotation or provide a controlled release formula or both. 91. A marijuana-based medical formula of Huaqiugu, Ganji, and _ ^ ^ 糸, which is obtained by a method such as any one of claims 73 to 90 of the scope of patent application. 92. For example, the patent application No. 54 ^ Beiyouzhule formula, which contains two types of cannabinol tetrahydrocannabinol (THCV) and subcannabinol (CBDV), wherein the amount of CBDB present is greater than THCV by weight Existed. % If the formulation of the scope of patent application No. 92, it contains ⑽ or thc or both. . As stated in the formula of the patent scope of item 92, where (^] 81 :) 乂 对 丁] 9 [(:: The weight ratio is higher than 1.5: 1. 5. As in the printed scope of the patent scope of formula 92 Wherein the weight ratio of cbdV to THCV is from about 99: 1 to about 1.5: 1. 96. For the formulation of item 95 of the patent application, wherein the weight ratio of CBDV to THCV is from about 20: 1 to about 2.5: 1. 97. If the formula of the scope of patent application is item 92, the weight ratio of the CBDV to THCV is about 9: 1. 98. If the formula of the scope of patent application item 92, the ratio of the CBDB to THCV is The weight ratio is about 5: 1 to 3: 1. (Please fill in the 5 items on the back of fiatt first) 76 1222882 Sat 3 -1-1 -—_ I___I .; Employees of the Intellectual Property Office of the Ministry of Economic Affairs, F8, BS, C8, D8, Patent Counseling 99. If you apply for the formula of the 92th patent scope, it does not contain other substances Cannabis species like cannabis. 100. The formulation according to item 92 of the patent application, wherein the CBDV and THCV form part of an extract obtained from a cannabis plant, and the extract contains all cannabinoids naturally occurring in the plant. 101. For the formulation of the scope of application for patent No. 100, the cannabis plant is selected from wild cannabis, Indian hemp, or genetically interleaved, self-interleaved, or hybrids thereof. 102. A method of variation such as the method of claim 73, wherein one or more dried cannabis plants are provided in step (a), the CBDV and THCV contents of which are known; and a pharmaceutical formula comprising a predetermined The weight ratio of CBDV to THCV replaces CBD and THC. 103. A pharmaceutical formula comprising two types of cannabinol: THC and THCV, wherein the amount of THCV present is approximately equal to or greater than the content of THC by weight. 104. For example, the pharmaceutical formula of item 103 of the patent application scope, wherein the weight ratio of THCV to THC is 99: 1 to 1.5: 1. 105. For example, the formulation of item 103 or 104 of the patent application scope, wherein the weight ratio of THCV to THC is about 17: 3. 106. If the formulation of the scope of patent application No. 103, it also contains CBD or CBDV or both and its content is less than THCV content by weight. 107: The formulation according to item 103 of the application, wherein the THCV and THC constitute a part of an extract obtained from a cannabis plant, and the extract contains all cannabinoids naturally occurring in the plant. 77 gg iCNS) / V; (2J0: >: χ) • Γ * equipment · --- (please fill in the alpha sound V on the back of Mts before filling in this card)-1222882 Six Consumer Goods Cooperatives, Intellectual Property Bureau, Ministry of Economic Affairs India ^ A8 B8 C8 D8 寻 Profit-seeking range ... The formula of item m in the patent application scope, where the hemp plant is selected from hemp, Indian hemp, or genetic interlacing, self-interlacing, or hetero-parent. -A method of variation such as the method in claim 73, wherein in step (i), one or more dried cannabis plants are provided, the THCV and THC content of which are known; and a preparation of a medical formula containing a predetermined weight ratio THCV is more than THC instead of CBD HC. A medical formula based on cannabis, which is obtained by methods such as patent application No. 102 or 109. m. The medical formula according to any one of claims 54, 91, 102, or 110, which is used to treat inflammatory diseases or any diseases or conditions that play a role in oxidative stress during their course. 112. A pharmaceutical formulation according to item 62 or 98 of the scope of patent application, which is used to treat rheumatoid arthritis or inflammatory bowel disease or Crohn's disease. 113. The pharmaceutical formula according to item 112 of the application, wherein in the formula, CBD and THC or CBDV and THC V or both constitute a part of an extract obtained from a cannabis plant, and the extract contains the plant naturally occurring All cannabis-like. 114. The pharmaceutical formula according to the scope of application of the patent No. 61 or 97, which is used for the treatment of mental disorders, epilepsy, dyskinesia, stroke, head injury or diseases requiring appetite suppression. 115: If the pharmaceutical formula of item 114 of the patent application scope, wherein in the formula, CBD and THC or CBDV and THCV or both constitute a part of an extract obtained from a hemp plant, the extract contains 78 naturally occurring in the plant (CNS) A ^ i (2JO 1222882 VI Scope of Patent Application All types of cannabis hope. 116. A pharmaceutical formula obtained by the method of applying for the scope of patents 73 or 102, comprising approximately equal amounts of CBD and THC or THCV and CBDV for the treatment of multiple sclerosis, chordal injury, peripheral neuropathy or other neurogenicity pain. 117. A pharmaceutical formula comprising a weight ratio of THC to CBD or THCV to CBDV of about 39: 1 to about 99: 1 for treating cancer pain or migraine or for appetite stimulation. 118. The pharmaceutical formula according to item 117 of the patent application, wherein the weight ratio of THC to CBD or THCV to CBDV is about 39: 1. 119. The pharmaceutical formula of item ip or 118 in the patent scope of May, wherein 'THC and CBD or THCV and CBDV or both of them constitute a part of an extract obtained from a cannabis plant, and the extract contains the Plants are naturally cannabis-like. 120. The pharmaceutical formula according to the scope of patent application No. 03, which is used to treat cancer pain or migraine or to stimulate appetite. 121. A medicinal product with an extended storage life, comprising cannabis dihydrazone (CBD) and one or more other biologically active components. 122. The pharmaceutical product of claim 121, wherein the biologically active component is a lipophilic substance. 123. The pharmaceutical product of item 122 in the scope of patent application, wherein the biological activity. The component is selected from the group consisting of cannabinol (CBN), cannabinol (CBG), butan HC, CBDV and THCV. 124. 1 item of pharmaceutical formula, including if you apply for a patent (please continue with the *: ij on the back and fill in this page first) ----- Order --- Printed by the Consumer Goods Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs ^ " Specification (2.K) 79 1222882 AS Βδ CS D8 Apply for the features of any one of the 54 to 72, 91 to 1 (Η, 103 to 108, or 110) scope of Liganwei. I25 · A pump action spray, including, for example, patent scope 1, 54, The pharmaceutical formula of any one of items 91, 108, or 110, wherein the formula is delivered through a nozzle, so that the average aerodynamic diameter of the particles produced is i 5 to 45 microns. 126.—for administration through a mucosal surface Its cannabis-based medical formula contains cannabinoids such as cannabis second age (CBD) and tetrahydrocannabinoid (tHC), or cannabis such as hypotetrahydrocannabinol (THCV) and subcannabindiol (CBDV) Phenol, where the formula is a liquid dosage form and can produce particles with an average aerodynamic particle size of 15 to 45 microns. 127. The pharmaceutical formula of item 126 in the patent claim, wherein the particle size is between 20 and 40 microns 128. For example, if you apply for a pharmaceutical formula under item 126, the average ㈣ is about 33 microns. 129. For example, if you apply for a pharmaceutical formula under item 126, which include cannabidiol (CBD) and tetrahydrocannabinol (THC) ) And other types of cannabis are expected to be approximately equal by weight. 130. The medical formula of the scope of application for patent No. 126 includes cannabinol (CBD) and tetrahydrocannabinol (THC) and other cannabinoids, in which the amount of thc is greater than the amount of CBD present by weight. 13L For example, the pharmaceutical formula of item 126 in the patent scope includes cannabis ages such as cannabis second age (CBD) and tetrahydrocannabin (THC), in which the amount of cbd by weight is greater than the amount of THC by weight. (CNS) A ^; (2j〇 First η Back: ί I φ then T Fill in, write this, page A, I order II, staff member of the Intellectual Property Bureau of the Ministry of Economic Affairs, Xiaoxian Cooperative Cooperative Seal · 80 1222882 A8 B3 C8 D8 Ministry of Economic Affairs Wisdom For the staff at the shoulder of the house ## 社 社 印 $ Application for a patent scope 132. If the patent scope of the patent application is No. 126 and ™: materials such as marijuana ^ 133 · If the patent scope of the patent application No. 126 of the medical formula, it is substantially free of Any other types of cannabinols that appear in the genus Cannabis. 134. If the pharmaceutical formula under the scope of patent application No. 126, the cbd and THC are in a substantially pure form. 135. If the pharmaceutical formula under the scope of patent application No. 126, It contains—or many other classes Cannabis. B6. If you apply for the pharmaceutical formula of item 135, the-or more other types of cannabis are hypotetrahydrocannabin (THCV) or hypocannabinol (CBDV) or both. 137. For example, the pharmaceutical formula of item 126 of the patent application, wherein the cbd and THC are derived from one or more extracts of one or more cannabis plants, and the one or more extracts contain all natural cannabinoids of the plant. 138. For example, please refer to the pharmaceutical formula of item 137, in which the cannabis plant is wild cannabis (Cannabis sativa), Indian cannabis (Cannabis indica), genetic interlacing, self-interlacing or hybrid. 139. The medical formula of item 138 in the patent application, wherein the cannabis plant is wild cannabis, the Indian subspecies and is selected from the Indian variant and the kafiristanica variant. H0. The pharmaceutical formulation under item 137 of the patent, which contains extracts from two or more different varieties of cannabis.如. For example, if you are applying for a medicine in the scope of patent application No. 137, the extract is made by extracting dried cannabis plants through supercritical or subcritical fluid (please note the note V on the back of Mt5 before filling in this page)- Binding --------- # II n 81 1222882 Equipment. 142. The pharmaceutical formulation of item 126 of the scope of patent application, which allows delivery of at least 1.0 mg of guabinol per omi liquid formulation. 143. The pharmaceutical formula of item 137 of the scope of patent application is a plant-based pharmaceutical product prepared from a plant-based pharmaceutical substance. 14 = Pharmaceutical formula in the scope of patent application No. 137, where each extract is transmitted from a specific chemovar.如 If the medical formula of item 143 of the patent application scope, the botanical drug substance has an HPLC curve, and the residence time of THC, CBD and CBN in the curve is 9 · 6_10 · 6 minutes, 5 4 5 9 minutes And 7.9-8 · 7 minutes. Η6. The pharmaceutical formula according to item 145 of the patent application scope, wherein the botanical drug substance comprises-CBD botanical drug extract having about 84% cbd and about 6% THC. The medical formula of the scope of application for patent No. 145, wherein the botanical drug substance comprises -THC botanical drug extract having about 89% coffee and about 6% CBD. The pharmaceutical formula of No. 126 in the scope of patent application of Oru includes the cannabis age such as hypotetrahydrocannabinoid age (THCV) and secondary cannabis (CBDV). Among them, the amount of CBDB present by weight is greater than that by Qing Existing amount. Such as the application of the patent formula 148, including coffee or THC or both. 150. If the medical formula of the scope of patent application No. 148 is applied, it is not substantially 82 Printed by Xiaoxian Cooperative of Employees of Intellectual Property Bureau, Ministry of Economic Affairs ¾ 1222882 Yinxian Cooperative, employee of the Intellectual Property Bureau of the Ministry of Economic Affairs, said Λ8 B3 C8 D8 VI. Application for profit-seeking Any other type of cannabinol present in the genus Cannabis. 151. As stated in the medical formula of item 148 of the patent, wherein the THCV and the THCV constitute part of an extract obtained from a cannabis plant, the extract contains all cannabinoids naturally occurring in the plant. 152. The pharmaceutical formula of item 151 in the patent application, wherein the cannabis plant is wild cannabis (Cannabis sativa), Indian cannabis (Ca_bis mchca), gene interlaced, self-interlaced or hybrid. 153. For example, the pharmaceutical formula of item 148 of the patent scope allows at least 1.0 mg of cannabinoid to be delivered per 10 mi of the liquid formula. 154. For example, the pharmaceutical formula of item 148 of the patent scope is a plant-based pharmaceutical product prepared from a plant-based pharmaceutical substance. ⑸. If you are applying for the pharmaceutical formula of item 126, do not present a propellant-driven aerosol or propellant-driven liquid spray formulation. 156. For example, the medicine Xiji Fang of the scope of application for patent No. 126, it is a pumping action spray formulation. 157 · —A method for preparing a medical formula based on hemp, the formula comprising CBD and THC or CBDV and DHCV, the method comprises the following steps: a) providing one or more dried cannabis plants, the cannabis plant contains CBD And THC or CBDV and THCV; b) preparing the one or more cannabis plant extracts; 0 using a material formula derived from the extract prepared in step (b); and d) using a pharmaceutically acceptable carrier or excipient The product of step (c) is formulated into a liquid pharmaceutical formulation. 83 1222882 A8 B3 C8 6. Applying for a profit-seeking range 158. As in the method of item 157 of the η-month patent, the pharmaceutical formulation of the liquid dosage form in step d) can produce particles having an average aerodynamic particle size of 15 to 45 microns. 159. The method of claim 157, wherein the step ， extract is prepared using one or more of the following procedures ... (0 impregnation (H) diafiltration (111) using a solvent such as Ci_C5 alcohols, Norfolk ( (Norflurane) or HFA227 extraction (iv) subcritical or supercritical fluid extraction. Vice. For example, the method of patent application No. 157, wherein before extraction, the dried cannabis is heated to about 60t to about 225 ° 俾Decarboxylate the acid form of any cannabinoid-like substance present in the extract. A method as described in item (1) of the patent application, wherein the dried cannabis is heated to about 100t to about 150t before extraction. Decarboxylation of any acidic form of cannabinoid present in the extract. 162. The method of claim 157, comprising extracting one or more cannabis plants using supercritical or subcritical carbon dioxide. 163. If the scope of the patent is claimed The method according to item 162, wherein after the extraction with supercritical or subcritical fluid, the extract is subjected to "wintering" and the wax is removed from the extract. 164: A medical formula based on hemp, which is obtained by applying Obtained by the method of item 157. 165.—A pharmaceutical formula for the administration of cannabinoids through the surface of the mucosa, (please fill in this page on the ii sound V on the back of Mtt) ---- Order-¾ Employees of the Intellectual Property Bureau of the Ministry of Economic Affairs, Cooperative Cooperatives ^ 1222882 A8 B3 C8 ____ D8 6. The scope of patent applications includes tetrahydrocannabinol (THC) and cannabidiol (CBD) and a matrix containing one or more self-emulsifiers and similar Cannabinol solubilizing agent. When hydrated, this agent forms an emulsion containing THC or CBD. The emulsion reversibly adheres to the surface of the mucosa and allows controlled release of THc and CBD. 166. Such as the scope of application for patent 165 Formula, in which the self-emulsifying agent and cannabinoid-based solubilizing agent are selected from the group consisting of: glyceryl monooleate, glyceryl monostearate, glycerol medium chain triglyceride, polyoxyethylene Castor oil, polyoxyethylene alkyl ether, polyoxyethylene ether, polyoxyethylene fatty acid ester, polyoxyethylene ethyl stearate, and polysorbate. 167. The formulation according to item 166 of the patent application scope, wherein the agent is a self-emulsifier and a cannabinoid-based solubilizing agent is polyoxyethylene castor oil. 168. For example, the formula in the scope of application for patent No. 166, which is a self-emulsifying agent and a cannabis-like increasing solvent, is a cremophoj. 169. If the formula of the scope of patent application is No. 166, which includes ethanol and the pharmaceutical agent which is a self-emulsifying agent and a cannabis-like increasing solvent is a cremophor 〇170. If the formula of the scope of patent application No. 165 The ratio of THC to CBD is selected from the following groups: the ratio of THC to CBD is 2: i, the ratio of THC to CBD is 1 · 1 and the ratio of THC to CBD is i: 2. 171. The formulation according to item 165 of the application, wherein the matrix comprises a plurality of thickeners. 172. The formulation of item ^ in the patent scope of Shenyan, where the matrix contains one (please fill in this page first with the urgent matter on the back of Mtt)-85 1222882 A8 B3 C8 D8 A hydrate forms a gel when hydrated, ^ S ηχ JL>, is a positive surface charge, and one or more tackifiers form a gel with a load when hydrated. ， ·, Surface electricity 173 · If the formula of the scope of application for the patent m, _ 4 viscidity agents are solubilized by the action of enzymes present in saliva. 174. The formulation according to item m of the patent application scope, wherein the thickener is a stone mountain water compound. & 175. If the formula in the scope of patent application is No. 171, the formula of the basin and a beta is viscose; 176. If the formula in the scope of patent No. 171 is requested, it is a gel, compressed or capsule dosage form. < & W 177. If the formulation of the scope of patent application No. 164, it is in the form of a gel for the administration of lipophilic drugs through the sublingual or buccal mucosa, or both, where the gel Or the gel spray forms a lipophilic drug-containing emulsion that adheres to the sublingual or mucous membrane or both. 178. A formulation according to item 164 of the application, which comprises one or more chef extracts. Printed by the Consumer Goods Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs ^ 179 · —A pharmaceutical formula for administering one or more cannabis extracts through a mucosal surface 'comprising one or more cannabis extracts and a matrix, the extracts containing cannabis II Cannabinoids such as phenol (CBD) and tetrahydrocannabinol (THC). The matrix contains one or more agents that are self-emulsifiers and cannabinoid solubilizers. When hydrated, the agent forms THC or CBD-containing agents. Emulsion, which reversibly adheres to the surface of the mucosa, and allows controlled release from the cannabis-like compound (CBD) and tetrahydrocannabis (THC) and other cannabis-like compounds 1228882 AS B8 C8 D8 6. Scope of patent application The extract of phenol releases these types of cannabinol. Jiruo claims the pharmaceutical formula of item 179 of the patent, which is a single-agent injury killing system of self-emulsifier and cannabis-like increasing solvent. It is composed of the following combinations: glyceryl monooleate, monohard Glyceryl fatty acid esters, medium-chain triglycerides, polyoxyethylene castor oil, polyoxyethylene alkyl ethers, polyoxyethylene ethers, t-oxyethylene fatty acid esters, polyoxyethylene ethyl stearate, and polyoxyethylene fatty acid esters Sorbitol 酉 Q (please fill in this page with the notes on the back of Mti) --------- Order, printed by the Consumer Goods Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs ii3 g λ :; 87